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Biomedical subjects

H Adachi

Publications and source records attributed to H Adachi.

At least 73 records · Page 4Linked to original sources

[Intravascular lymphomatosis: a case report].

We report a case of a 64-year-old man with intravascular lymphomatosis. He had dementia and generalized seizure. Computed tomogram scan and magnetic resonance imaging showed multiple infarctions in the right frontal lobe, right cerebellar hemisphere and left occipital lobe. A month after admission he had a daily high fever and frequent convulsions. The level of serum LDH was progressively getting higher and the level of beta 2-microglobulin in both serum and CSF was high. One and a half months after admission we performed an open biopsy for making a definite diagnosis by pathological examination. Histological diagnosis was intravascular lymphomatosis (angiotrophic lymphoma) of large B cell type. He was treated with regimens of combined chemotherapy with M-CHOP (methotrexate, cyclophosphamide, adriamycin, vincristine, prednisolone). After chemotherapy his consciousness was gradually improving better and the level of serum LDH and beta 2-microglobulin was reduced to a low level. Three months after admission he died of respiratory failure. After a review of the literature and experience with this case, it is obrious that early diagnosis of this disease is difficult. However, we think that multiple cerebral infarctions on neuroradiological examinations and high levels of serum LDH (especially LDH2 and LDH3) and beta 2-microglobulin in CSF and serum should lead to a presumptive diagnosis of this disease, and biopsy should be used to make a difinite diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗

[Subacute cor pulmonale due to microscopic pulmonary tumor embolism].

We report a case of subacute pulmonary hypertension caused by microscopic pulmonary tumor embolism due to the dissemination of gastric cancer cells. The patient, a 61-year-old man with no history of malignant diseases, was admitted to our hospital on October 14 in 1998 because of cough and dyspnea on effort, that had developed since the previous month. On admission, chest radiography including CT scans showed slight cardiomegaly and disseminated reticulonodular shadows predominating in the lower lung fields of both lungs, and arterial blood gas analysis disclosed severe hypoxemia. Lung perfusion scintigraphy revealed multiple irregular defects in both lungs. Echocardiography indicated right ventricular overload, and the pulmonary artery systolic pressure was estimated to be higher than 80 mmHg. Disseminated intravascular coagulation (DIC) developed on the 6th day of hospitalization. Multiple pulmonary embolism with DIC of unknown cause was diagnosed, and the patient was given anticoagulant therapy with heparin. However, he died of respiratory failure on the 7th day of hospitalization. At autopsy, an invasive cancer was found in the stomach, resembling type IIc early gastric cancer. The lumens of the pulmonary arterioles were significantly narrowed by fibrocellular proliferation and thrombi accompanying tumor cell clusters, and some of the microvessels were completely occluded. Disseminated microscopic pulmonary metastasis of malignant tumors should be included in the differential diagnosis of subacute pulmonary hypertension due to multiple pulmonary embolism of unknown cause.

Acute Disease↗

[Strategy for post coronary artery bypass grafting in patients with bypass graft stenosis: comparison of percutaneous transluminal coronary angioplasty for the native coronary artery, internal mammary artery and saphenous vein graft].

OBJECTIVES: The strategy for post coronary artery bypass grafting (CABG) was investigated in patients with graft stenosis. METHODS: The study included 123 post-CABG patients with graft stenosis. The patients were divided into three groups according to target vessels; saphenous vein graft (SVG; n = 72), internal mammary artery (IMA; n = 21) and native coronary artery (n = 30). Furthermore, SVG lesions were divided into proximal anastomosis (n = 23), body (n = 40) and distal anastomosis (n = 9). The procedural success rate and late patency rate were compared between the three groups. Furthermore, the relationships between pre percutaneous transluminal coronary angioplasty (PTCA) percentage diameter stenosis, procedural success rate and late patency rate were evaluated. RESULTS: Procedural success rate was similar in the three groups, but late patency rate was higher in the IMA group. Procedural success rate and late patency rate were significantly lower in proximal anastomoses compared to other sites of SVG stenoses, IMA group and native coronary artery group (p < 0.05). Totally occluded native coronary artery lesions had a high procedural success rate compared with occluded IMA and SVG lesions, but the late patency rate was not higher. Procedural success rate showed no significant difference for 75-99% stenotic lesions, but the late patency rate was significantly higher in the IMA group (p < 0.05). Patients in the stenting group had a greater late patency rate compared with the balloon angioplasty group. There was no significant difference in late patency rate between the IMA group and SVG group. CONCLUSIONS: Late patency rate of the IMA is higher than that of the native coronary artery. SVG with proximal anastomosis and severe stenosis shows a significantly lower late patency rate than the native coronary artery. Therefore, PTCA should be considered for the native coronary artery in the absence of chronic total occlusion.

Aged↗

[Efficacy of simultaneous bolus injection of lidocaine with propofol on pain caused by propofol injection].

To investigate the effect of simultaneous bolus injection of 2% lidocaine 2 ml on preventing the pain on propofol injection, 80 patients were randomly assigned to one of four study groups; Group I received simultaneous bolus injection of 2% lidocaine 2 ml with infusion of propofol; Group II received bolus injection of saline 2 ml, 10 s before the start of infusion of propofol-lidocaine mixture; Groups III and IV received bolus injections of lidocaine and saline, separately 10 s before starting propofol infusion. Incidence of propofol-induced pain was significantly more frequent (P < 0.001) in Group IV (70%) than in the other groups (20% each). Number of patients who were satisfied with this anesthetic induction and requested for the same induction method in the next anesthesia was significantly larger in the groups receiving lidocaine (P < 0.05). Simultaneous bolus injection of lidocaine with propofol showed a similar clinical efficacy compared with both preadministration and premixing of lidocaine in preventing the propofol-induced pain.

Adult↗

Molecular identification of a rat novel organic anion transporter moat1, which transports prostaglandin D(2), leukotriene C(4), and taurocholate.

We have isolated a rat novel multispecific organic anion transporter, moat1. The isolated clones were originated by alternative splicing of the moat1 mRNA. The nucleotide sequences predict a protein of 682 amino acids with moderate sequence similarity to LST-1, the oatp family, and the prostaglandin transporter. Northern blot analysis of rat moat1 identified a predominant transcript of 4.4 kilonucleotides in all tissues. Northern blot and in situ hybridization analyses of rat brain further indicated that moat1 mRNA is widely distributed in neuronal cells of the central nervous system, especially in the hippocampus and cerebellum. moat1 transports prostaglandin D(2) (K(m); 35.5 nM), leukotriene C(4) (K(m); 3.2 microM) and taurocholate (K(m); 17.6 microM) in a sodium-independent manner. moat1 also transports prostaglandin E(1), E(2), thromboxane B(2), and iloprost but not dehydroepiandrosterone sulfate and digoxin, of which the substrate specificity is similar, but definitively different from those of any other organic anion transporters.

Alternative Splicing↗

All eight stereoisomeric D-glyconic-delta-lactams: synthesis, conformational analysis, and evaluation as glycosidase inhibitors.

An efficient and general synthetic route to all eight stereoisomeric D-glycono-delta-lactams has been developed. The strategy involves, as a key step, a stereodivergent delta-lactam formation with configurational retention or inversion at C-4 of a starting gamma-lactone to lead to two epimers of delta-lactam from one parent gamma-lactone. Conformations of eight glycono-delta-lactams were examined by X-ray crystallographic analysis and molecular modeling. Analyses of conformation and glycosidase-inhibition provide useful information for the design of new glycosidase inhibitors.

Animals↗

4-(3-Chloro-4-methoxybenzyl)aminophthalazines: synthesis and inhibitory activity toward phosphodiesterase 5.

We synthesized various 4-(3-chloro-4-methoxybenzyl)aminophthalazines substituted at the 1- and 6-positions and evaluated their inhibitory activity toward phosphodiesterase 5 (PDE5) and their vasorelaxant activity in isolated porcine coronary arteries precontracted with prostaglandin F2alpha (10(-5) M). The preferred substituents at the 1-position of the phthalazine were 4-hydroxypiperidino, 4-hydroxymethylpiperidino, 4-(2-hydroxyethyl)piperidino, and 4-oxopiperidino. Among these compounds, [4-(3-chloro-4-methoxybenzyl)amino-1-(4-hydroxy)piperidino]-6-phthala zinecarbonitrile monohydrochloride (13) exhibited potent PDE5 inhibitory activity (IC(50) = 0.56 nM) with >1700-fold high selectivity over other PDE isozymes (PDE1-4). Compound 13 exhibited the most potent vasorelaxant action (EC(50) = 13 nM) in this series of compounds. Compound 13 reduced mean pulmonary arterial pressure by 29.9 +/- 3.1% when administered intravenously at 30 microg/kg to the chronically hypoxic rats and had an apparent oral bioavailability of about 19.5% in rats and was selected for further biological evaluation.

3',5'-Cyclic-GMP Phosphodiesterases↗

Characterization of a C-terminal-type kinesin-related protein from Dictyostelium discoideum.

We have determined the full sequence of K2, a kinesin-related protein (KRP) in Dictyostelium discoideum. Sequence homology and domain organization placed K2 in the ncd/Kar3 subfamily of the C-terminal-type KRPs. Bacterially expressed, truncated K2 showed ATP-dependent binding to microtubules and microtubule-stimulated ATPase activity. K2-null cells grew and developed normally, suggesting overlapping functions of K2 with other microtubule motor(s). Overexpression of K2 caused partial mitotic arrest. Green fluorescent protein-tagged full-length K2 localized in the nucleus at the interphase and on the mitotic spindle during mitosis. These results suggest that K2 is a microtubule-dependent motor which may play some roles in mitotic spindles.

Amino Acid Sequence↗

Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I.

The scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters from high-density lipoprotein (HDL) and cholesterol secretion into bile in the liver. In this study, we identified an SR-BI-associated protein from rat liver membrane extracts by using an affinity chromatography technique. This protein of 523 amino acids contains four PDZ domains and associates with the C terminus of SR-BI by using its N-terminal first PDZ domain. Therefore, we denoted this protein as CLAMP (C-terminal linking and modulating protein). CLAMP was located mostly in the sinusoidal membranes, whereas SR-BI was detected in both sinusoidal and canalicular membranes. After the solubilization of the liver membranes with Triton X-100, SR-BI was immunoprecipitated with anti-CLAMP monoclonal antibody, suggesting the association of these proteins in vivo. By coexpressing SR-BI with CLAMP in Chinese hamster ovary cells, we observed (i) the increase in the expression level of SR-BI, (ii) the reduction in the deacylation rate of the cholesteryl esters taken up from HDL, and (iii) the change in the intracellular distribution of fluorescent lipid 1,1'-dioctadecyl-3,3, 3',3'-tetramethylindocarbocyanine percholate taken up from HDL. Taken together, these data suggest that CLAMP, a four-PDZ-domain-containing protein, is associated with SR-BI in the liver sinusoidal plasma membranes and may modulate the intracellular transport and metabolism of cholesteryl esters taken up from HDL.

Amino Acid Sequence↗

Novel Dictyostelium unconventional myosin, MyoM, has a putative RhoGEF domain.

We have cloned a novel unconventional myosin gene myoM in Dictyostelium. Phylogenetic analysis of the motor domain indicated that MyoM does not belong to any known subclass of the myosin superfamily. Following the motor domain, two calmodulin-binding IQ motifs, a putative coiled-coil region, and a Pro, Ser and Thr-rich domain, lies a combination of dbl homology and pleckstrin homology domains. These are conserved in Rho GDP/GTP exchange factors (RhoGEFs). We have identified for the first time the RhoGEF domain in the myosin sequences. The growth and terminal developmental phenotype of Dictyostelium cells were not affected by the myoM(-) mutation. Green fluorescent protein-tagged MyoM, however, accumulated at crown-shaped projections and membranes of phase lucent vesicles in growing cells, suggesting its possible roles in macropinocytosis.

Amino Acid Sequence↗

Vasorelaxant effect of a phosphodiesterase 3 inhibitor, olprinone, on isolated human radial artery.

The radial artery is currently used as a viable arterial conduit for myocardial revascularization. The aims of this study were to identify phosphodiesterase 3 isoenzyme in the human radial artery isolated for coronary artery bypass grafting, and to examine the vasorelaxant effect of a cardiotonic and vasodilating phosphodiesterase 3 inhibitor, 1, 2-dihydro-6-methyl-2-oxo-5-(imidazo[1,2-a]pyridin-6-yl)-3-pyridine carbonitrile hydrochloride monohydrate (olprinone). The phosphodiesterase 3 isoenzyme was separated from the radial artery by DEAE-Sepharose chromatography. Olprinone inhibited the phosphodiesterase 3 activity with an IC(50) value of 1.25 microM. Olprinone relaxed the phenylephrine-induced contractions of endothelium-denuded arterial strips with an EC(50) value of 0. 107+/-0.029 microM (n=5). These findings indicate that the human radial artery possesses phosphodiesterase 3 isoenzyme activity and olprinone causes potent relaxation of the arterial strip in vitro through inhibition of phosphodiesterase 3 isozyme activity.

Endothelium, Vascular↗

Flexible synthesis and biological activity of uronic acid-type gem-diamine 1-N-iminosugars: a new family of glycosidase inhibitors.

An efficient and flexible synthetic route to four gem-diamine 1-N-iminosugars of uronic acid-type (D-glucuronic, D-mannuronic, L-iduronic, and L-guluronic acid), a new family of glycosidase inhibitor, from l-galactono-1,4-lactone have been developed in an enantiodivergent fashion through a sequence involving as the key steps (a) the formation of gem-diamine 1-N-iminopyranose ring by the Mitsunobu reaction of an aminal and (b) the introduction of a carboxylic acid group by the Wittig reaction of a ketone, hydroboration and oxidation, and the Sharpless oxidation. D-Glucuronic and D-mannuronic acid-type 1-N-iminosugars, (3S,4R,5R, 6R)- and (3S,4R,5R,6S)-4, 5-dihydroxy-6-trifluoroacetamido-3-piperidinecarboxylic acid, were proven to be potent inhibitors for beta-D-glucuronidase (IC(50) 6.5 x 10(-)(8)M) and to affect human heparanase (endo-beta-glucuronidase).

Animals↗

Does repeated balloon inflation during coronary angioplasty induce ischemic tolerance? Analysis based on regional work.

It has been reported that repeated brief balloon inflation during coronary angioplasty (PTCA) alleviates myocardial dysfunction. However, it has also been reported that PTCA does not induce ischemic tolerance. Six patients with stable angina pectoris were recruited for this study. They were scheduled for PTCA to a significant stenosis of the proximal left anterior descending artery (LAD). All patients had single-vessel coronary artery disease without angiographic evidence of collateral circulation and with normal wall motion. After the stenosis of LAD was dilated by a 30-s inflation, 60 s of balloon inflation was performed five times at 60-s intervals. Left ventricular regional work was determined in the first and fifth inflations, and the data were compared. Regional work of the interventricular septum decreased immediately after the balloon inflation (the first inflation: 5.3 +/- 1.0 --> 0.6 +/- 0.2 mJ/cm3; fifth inflation; 5.3 +/- 1.0 --> 0.6 +/- 0.3 mJ/cm3) and no statistically significant differences were found between the first and fifth inflations. After balloon deflation, the time required for the recovery of regional work was 30s in the fifth inflation, compared with 40 s in the first inflation (at 30 s after deflation, first inflation: 3.6 +/- 1.3 mJ/cm3; fifth inflation: 5.2 +/- 1.2 mJ/cm3). Although repeated balloon inflation did not change the amount of reduction in regional work, it improved the postischemic recovery of regional work. These results suggest ischemic tolerance.

Aged↗

Thymidine phosphorylase expression results in a decrease in apoptosis and increase in intratumoral microvessel density in human gastric carcinomas.

Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth factor (PD-ECGF) is expressed at higher levels in a variety of human carcinomas than in adjacent normal tissue. The higher expression is associated with an increase in intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. This study examined the role of dThdPase in apoptosis, IMVD and p53 expression in human gastric carcinomas, dThdPase expression was noted in 12 (35.3%) of 34 early carcinomas, and in 20 (55.6%) of 36 advanced carcinomas. At least 10 areas consisting of carcinoma cells with diffuse dThdPase expression from the 32 dThdPase-positive tumors (category I), and 10 areas without dThdPase expression from the 38 negative tumors (category II) were selected from each case. For early gastric carcinoma, the mean IMVD was 88.8+/-19.4 in category I and 61.4+/-17.3 in category II carcinomas, while for advanced gastric carcinoma, the mean IMVD was 98.8+/-21.0 in category I and 76.0+/-27.1 in category II carcinomas. The mean IMVD was significantly higher in category I than in category II tumors (P<0.05). The mean apoptotic index (AI: percentage of apoptotic cells) was 1.95+/-1.30 in category I, and 3.76+/-1.49 in category II carcinomas for early gastric carcinoma, and 1.51+/-0.98 in category I and 2.14+/-0.66 in category II carcinomas for advanced gastric carcinoma, the value of the mean AI being significantly (P<0.05) higher in dThdPase-negative tumors (category II) than in the positive tumors (category I), regardless of tumor stage or histological type. There was a significant inverse correlation (P<0.001) between AI and IMVD. These results indicate that dThdPase expression is associated with both an increase in intratumoral microvessels and a decrease in apoptosis in human gastric carcinomas.

Adenocarcinoma↗

Early and late surgical outcomes of acute type A aortic dissection in patients aged 75 years and older.

BACKGROUND: With the general increase in human lifespan, aortic surgeons are faced with an increasing prevalence of acute type A aortic dissection in the elderly. In this study, we reviewed early and late surgical outcomes of acute type A dissection (operation within 48 hours after onset) in patients aged 75 years and older. METHODS: Between 1990 and 1999, 109 patients underwent emergency operation for acute type A dissection at Omiya Medical Center. Twenty-three patients were aged 75 years and older (elderly group, mean age, 79.1 +/- 4.7 years) and 86 were younger than 75 years old (younger group, mean age, 58.7 +/- 10.8 years). Early and late outcomes of both groups were compared. RESULTS: The hospital mortality rates were 13.0% (3 of 23) in the elderly group and 10.5% (9 of 86) in the younger group (p = 0.71). In the elderly, actuarial survival rate (including the operative mortality rate) at 1, 3, and 5 years was 78% +/- 9% for each point. In the younger group, the rates were 88% +/- 4% at 1 year, 83% +/- 4% at 3 years, and 81% +/- 5% at 5 years (p = 0.57). Actuarial event-free rates were 84% +/- 8% at 1 year, 77% +/- 11% at 3 years, and 77% +/- 11% at 5 years in the elderly group. In the younger group, the rates were 96% +/- 2% at 1 year, 88% +/- 4% at 3 years, and 81% +/- 7% at 5 years (p = 0.27). CONCLUSIONS: No significant differences in the hospital mortality, actuarial survival, or event-free rates were observed between the two groups. Operation for type A acute aortic dissection in patients aged 75 years or older can be performed with acceptable risk of death, and long-term results are satisfactory.

Actuarial Analysis↗

Subacute hepatic failure associated with a new antidiabetic agent, troglitazone: a case report with autopsy examination.

An autopsy case of fatal subacute hepatic failure after administration of troglitazone is described. The liver dysfunction developed about five months after the patient, a sixty-three-year-old woman, had been initially treated with troglitazone. The patient developed hepatic failure and died despite various hepatic auxiliary treatments such as plasmapheresis. Autopsy findings revealed focal liver cell necrosis, cholestasis and steatosis with infiltration of lymphocytes and neutrophils and lack of regenerative activity. The causative mechanism of liver dysfunction may be metabolite aberration, as a result of accumulation of hepatotoxic metabolite(s), in a category of idiosyncratic liver injury. It is proposed to monitor liver function strictly and periodically for the diabetic patients prescribed troglitazone.

Chromans↗

The role of obesity in the association of cardiovascular risk factors and glucose intolerance in small Japanese and North American communities.

To investigate whether the influence of obesity on cardiovascular risk factors and glucose intolerance differs between Japan and the US, we conducted cross-sectional surveys in those with elevated plasma glucose in Tanushimaru, Japan, and a stratified random population sample, in Wadena, MN. Subjects numbered 204 in Tanushimaru and 334 in Wadena. Body mass index (BMI), blood pressure, blood lipids, fasting plasma levels of glucose, glycosylated hemoglobin A(1c,) insulin, and free fatty acids were assessed. Overweight was defined as BMI of 27.5-29.9 kg/m(2) and obesity as BMI> or =30 kg/m(2). Gradual increases in risk factors were seen as BMI increased in both studies. Most risk factors were associated with glucose intolerance, except for BMI in Tanushimaru. In Wadena, glucose intolerance increased sharply among the obese. Adjustment for BMI attenuated the associations of cardiovascular risk factors with glucose intolerance in Wadena, but not in Tanushimaru. Obesity has an exaggerated influence on risk factors, compared with being overweight. The associations of glucose intolerance with cardiovascular risk factors are more affected by adjustment for BMI in Wadena than in Tanushimaru, not because of a different influence of body weight on risk factors between the two cities, but because obesity is rare in Japan.

Adult↗