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Biomedical subjects

S Haruta

Publications and source records attributed to S Haruta.

At least 37 records · Page 2Linked to original sources
PubMed1998

Absorption behavior of orally administered drugs in rats treated with propantheline.

The effect of gastrointestinal (GI) transit rate on the absorption behavior of orally administered drugs was investigated using rats pretreated with propantheline. The propantheline-treatment reduced the transit rate in all segments to approximately 50%. The absorption behavior was examined for three model drugs with different absorption characteristics: theophylline as a highly absorbable drug without the first-pass elimination, ampicillin as a poorly absorbable one, and cephalexin as a highly absorbable one via carrier-mediated transport system. In the GI transit-retarded state, the Tmax of the plasma concentration-time curve was delayed in all the three drugs. However, the extent of bioavailability was not changed in theophylline and cephalexin. On the other hand, the extent of bioavailability of ampicillin was increased in rats pretreated with propantheline. This might be caused by the increased residence time in the absorption site, i.e., small intestine. These results were generally predicted by use of the convolution method based on the GI-Transit-Absorption Model, which was developed in our previous study, using the GI transit rate parameters in rats pretreated with propantheline. The analysis using this model could clarify that the substantial absorption site of cephalexin moved to the upper region of the small intestine by the reduction of the GI transit rate.

Ampicillin↗
PubMed1998

Resistance to oxyimino beta-lactams due to a mutation of chromosomal beta-lactamase in Citrobacter freundii.

The duplicative mutation of an Ala-Val-Arg sequence at positions 208 to 210 in the loop structure of Enterobacter cloacae class C beta-lactamase caused substrate specificity extension to oxyimino beta-lactam antibiotics and this chromosomal mutation provided bacterial cells with high resistance to the beta-lactams (M. Nukaga et al, 1995, J. Biol. Chem. 270, 5729-5735). In order to confirm the universality of this phenomenon among other class C beta-lactamases, the duplicative mutation was applied to a class C beta-lactamase of Citrobacter freundii, which has 74% homology to the E. cloacae beta-lactamase amino acid sequence. The counterpart sequence to the Ala-Val-Arg of the E. cloacae enzyme in C. freundii beta-lactamase was identified to be Pro-Val-His. A Pro-Val-His sequence was inserted just after the native Pro-Val-His sequence at positions 208 to 210 in the C. freundii beta-lactamase. The resulting mutant of C. freundii beta-lactamase obtained a striking characteristic that we expected, showing substrate specificity extension to oxyimino beta-lactams. Nearly the same result was obtained with the insertion of an Ala-Val-Arg sequence after the native Pro-Val-His sequence. These results indicate that structural modification of this locus commonly induces modification of the substrate specificity to unfavorable substrates for many chromosomal class C beta-lactamases produced by gram-negative bacteria.

Amino Acid Sequence↗
PubMed1997

Intravascular ultrasound findings after successful primary angioplasty for acute myocardial infarction: predictors of abrupt occlusion.

OBJECTIVES: This study sought to evaluate the intravascular structure as depicted by intravascular ultrasound after successful primary angioplasty (i.e., without thrombolytic therapy) for acute myocardial infarction and to investigate the related predictors of acute coronary occlusion. BACKGROUND: The usefulness of primary angioplasty for acute myocardial infarction is still limited by early reocclusion. There are few data regarding the intravascular ultrasound findings after primary angioplasty. METHODS: Intravascular ultrasound was performed in 27 patients after successful primary angioplasty. Repeat coronary angiography was performed 15 min later, on the following day and 1 month after angioplasty. RESULTS: Abrupt occlusion occurred in 8 of 27 patients. Angiographic variables in patients with versus those without abrupt occlusion were not significantly different. Intravascular ultrasound disclosed a significantly smaller lumen area ([mean +/- SD] 2.49 +/- 0.72 vs. 5.06 +/- 1.52 mm2, p < 0.001) and a significantly greater percent plaque area (80.5 +/- 9.1% vs. 63.7 +/- 7.8%, p < 0.001) in patients with abrupt occlusion. There was no significant difference in external elastic membrane cross-sectional area. We classified the ultrasound appearance of the intravascular structure as smooth, irregular or filled. Abrupt occlusion occurred in none of 6 patients with a smooth intravascular structure, 24% of 17 patients with an irregular structure and in all 4 with a filled structure (p < 0.05). In the latter group, the lumen was filled with bright speckled or low echogenic material, although angiography revealed excellent coronary dilation in all these arteries. CONCLUSIONS: Intravascular ultrasound revealed a narrow lumen in coronary arteries showing abrupt occlusion after successful primary angioplasty, even though angiography disclosed successful dilation. Arteries with a lumen filled with bright speckled or low echogenic material frequently develop abrupt occlusion.

Aged↗
PubMed1997

Prediction of the plasma concentration profiles of orally administered drugs in rats on the basis of gastrointestinal transit kinetics and absorbability.

A new method based on gastrointestinal transit kinetics has been developed for estimation of the absorption profiles of drugs administered orally as aqueous solutions. The utility of the method was evaluated in rats. The gastrointestinal transit profile for each segment was estimated by in-vivo studies using phenol red, an unabsorbable marker. The gastrointestinal transit profile of phenol red was well explained by a linear gastrointestinal transit kinetic model with eight segments. We also introduced the absorption process into the gastrointestinal transit kinetic model and the plasma profile was predicted by the convolution method. The absorbability of drugs in each segment was assessed by an in-situ absorption study. The validity of the model was evaluated for model drugs with different absorption characteristics. The plasma profiles predicted for ampicillin, theophylline and cephalexin were in good agreement with those observed. The overestimated plasma profile of propranolol suggests that the low bioavailability of propranolol is a result of first-pass metabolism by the intestine wall and the liver, because the calculated absolute absorption is almost perfect. This proposed model is also suitable for estimation of segmental absorption, which is useful for the development of drug delivery systems. We have demonstrated that the plasma profile of orally administered drugs can be predicted by use of gastrointestinal transit and segmental absorbability information and that this method is especially useful for estimating separately the effect of absolute absorption and first-pass metabolism on the bioavailability of drugs.

Administration, Oral↗
PubMed1996

[A case of coronary artery embolism after double valve replacement].

A 69-year-old woman with combined valvular heart disease (mitral regurgitation and aortic regurgitation), ascending aortic aneurysm, and atrial fibrillation underwent double valve replacement (DVR) and, ascending aortic wall plication. The postoperative thrombo-test level was around 20%. The ST elevation on ECG (II, III, aVFm, V4 approximately V6) with chest pain were recognized on the 13 th postoperative day. She was diagnosed as having acute myocardial infarction, and percutaneous transluminal coronary recanalization was performed immediately. The coronary angiogram showed occlusion at the left anterior descending branch (#8). This lesion could be recanalized by 6,000 U plasminogen pro activator (pro-UK) administration. The cineangiogram on the 35th postoperative day, revealed complete recanalization of this occlusion. Several cases of acute myocardial infarction associated with valvular heart diseases has been reported previously in Japan. However, there has been no report, except for this case, demonstrating occlusion in the coronary artery after prosthetic replacement and successful PTCR. So, this case is the first report on that point.

Aged↗
PubMed1996

[Changes of coronary artery diameter during follow-up in patients with vasospastic angina: comparison of spastic and non-spastic sites].

The relationship between coronary vasospasticity and the development of atherosclerotic lesion was studied in 24 patients with vasospastic angina. All patients had no organic stenosis initially and underwent follow-up coronary angiography at 66 +/- 9 months after the initial examination. The coronary artery diameter was measured with the contour detection method. The spastic and non-spastic sites were identified at the initial coronary angiography with the acetylcholine provocation test. The change of the luminal diameter (delta LD) and the ratio of the change of luminal diameter (% delta LD) were compared at the spastic and the non-spastic sites. The follow-up examination showed significant decreases of coronary artery diameter in both the spastic (2.35 +/- 0.67 vs 2.16 +/- 0.58 mm, p < 0.001) and non-spastic sites (2.66 +/- 0.91 vs 2.54 +/- 0.84 mm, p = 0.02). However, delta LD and % delta LD were not different between the spastic and non-spastic sites (delta LD: -0.19 +/- 0.40 vs -0.12 +/- 0.46 mm, NS; % delta LD: -6.7 +/- 14.8% vs -3.2 +/- 17.0%, NS). In conclusion, coronary vasospasticity does not promote the development of atherosclerotic lesion.

Aged↗
PubMed1995

Molecular evolution of a class C beta-lactamase extending its substrate specificity.

Enterobacter cloacae GC1, a clinical strain isolated in 1992 in Japan, was found to produce a chromosomal class C beta-lactamase with extended substrate specificity to oxyimino beta-lactam antibiotics, significantly differing from the known E. cloacae beta-lactamases such as the P99 beta-lactamase. The 1560 nucleotides including the GC1 beta-lactamase gene were sequenced, and the amino acid sequence of the mature enzyme comprising 364 amino acids was deduced. A comparison of the amino acid sequence with those of known E. cloacae beta-lactamases revealed the duplication of three amino acids at positions 208-213, i.e. Ala-Val-Arg-Ala-Val-Arg. This duplication was attributed to a tandem duplication of a 9-nucleotide sequence. The chimeric beta-lactamases produced by the chimeric genes from the GC1 and P99 beta-lactamase genes indicated that the extended substrate specificity is entirely attributed to the 3-amino acid insertion. Two mutant beta-lactamases were prepared from P99 beta-lactamase by site-directed mutagenesis, i.e. an Ala-Ala-Ala sequence was inserted before or after the native Ala-Val-Arg at positions 208-210. These mutant enzymes revealed that the Ala-Val-Arg located from positions 211 to 213 in the GC1 beta-lactamase are the newly inserted residues, and this phenomenon is independent of the characteristics of the amino acids inserted.

Amino Acid Sequence↗
PubMed1995

Cytoplasmic body myopathy with hypertrophic cardiomyopathy.

A patient with cytoplasmic body myopathy presented muscle hypotonia from birth and developed progressive muscular atrophy and weakness, scoliosis, contracture of joints and cardiorespiratory failure. At the age of 17, he died of heart failure. Post mortem examination revealed severe hypertrophy of cardiac walls and generalized muscular atrophy. Microscopic examination showed many cytoplasmic bodies in skeletal muscle fibers and myofiber disarray in myocardium. No cases of cytoplasmic body myopathy with hypertrophic cardiomyopathy have been reported previously. It is suggested that the Z-line component is related to the formation of the cytoplasmic body in skeletal muscle and disarray in the cardiac muscle.

Adolescent↗
PubMed1993

[A case of transtentorial upward herniation due to cerebellar infarction manifesting upward gaze palsy as an initial sign].

Transtentorial upward herniation is a rare complication of cerebellar infarction and its development indicates an emergency and necessity of posterior cranial fossa decompression. A 63-year-old man with a history of myocardial infarction was admitted to the hospital complaining of sudden onset of vertigo and headache. Neurological examination revealed marked upward gaze palsy, right blepharoptosis, facial weakness, hearing loss on the left side and ataxia of the left upper and lower extremities. A few hours later, he rapidly lost consciousness and MRI revealed massive infarction in the left cerebellar hemisphere and transtentorial upward herniation. Immediate surgical decompression of the posterior cranial fossa was performed, thereafter patient gradually improved. This case suggests that upward gaze palsy is an important initial sign of transtentorial upward herniation with massive cerebellar infarction.

Cerebellar Diseases↗
PubMed1992

[A case of aortic valve stenosis and regurgitation with idiopathic thrombocytopenic purpura].

A patient of aortic valvular disease with idiopathic thrombocytopenic purpura underwent aortic valvular replacement. We report a preventive measure against the intra and postoperative bleeding. The patient was a 67-year-old man. He was diagnosed as aortic valvular stenosis with regurgitation. There was no abnormal data about the coagulation test. Thrombocyte count was 8.2 x 10(4)/mm3, but thrombocytopenic life span had shortened 3.8 days. So, we used gamma-globulin 400 mg/kg/day for 5 days before the day of operation and infused blood platelets on the day of operation. There was no problem intra and postoperative period. On the 14th postoperative day thrombocyte count increased to 22.9 x 10(4)/mm3, and thrombocytopenic life span returned to normal range (7.6 days). But on the 45th day of postoperation, thrombocyte count decreased to 11.0 x 10(4)/mm3. We think that many gamma-globulin medication is a useful method to prevent intra and postoperative bleeding resulting from idiopathic thrombocytopenic purpura.

Aged↗
PubMed1989

[A case of marked exercise-induced ST segment depression in anterior precordial leads with inferoposterior left ventricular aneurysm and significant stenosis of left anterior descending artery].

A 71-year-old man was admitted to a community hospital and diagnosed as having acute infero-posterior myocardial infarction. Severe ST segment depression occurred in anterior precordial leads with only 50 m walking, but he had no chest pain. He was then admitted to our hospital. Left ventriculography showed infero-posterior dyskinesis and aneurysm formation. Coronary angiography revealed triple-vessel disease including 90% stenosis at distal site of left anterior descending artery. Exercise thallium-201 myocardial scintigraphy by ergometer showed no filling defect in the anterior segment, though severe ST depression appeared in anterior precordial ECG leads. Infero-posterior segment showed persistent defect. We performed intravenous digital ventriculography at rest and during atrial pacing. Anterior wall motion during pacing was shown to be normal by amplitude and phase analysis. At the same time, the motion of the inferior wall was seen as abnormal and ST segment depression on anterior precordial leads appeared. We considered that in this case the anterior ST depression did not mean anterior myocardial ischemia but might be due to dyskinetic movement of the infero-posterior aneurysm.

Aged↗
PubMed1987

A family of Becker's progressive muscular dystrophy with severe cardiomyopathy.

A family of Becker's muscular dystrophy with marked cardiomyopathy was studied. The propositus, a 16-year-old boy with marked pseudohypertrophy in calves, showed electrocardiographic abnormalities resembling those in the Duchenne's type. Radionuclide study and endomyocardial biopsy revealed remarkable degeneration of myocardium. His uncle, who also had slight proximal muscular atrophy and weakness, and calves' pseudohypertrophy, died of heart failure at the age of 47, and autopsy showed dystrophic changes in skeletal muscles and extensive myocardial damage. Severe cardiac involvement can occur in Becker's muscular dystrophy which has been known to have an essentially benign clinical course, and radionuclide investigation is useful for the detection of preclinical cardiac lesions in patients with muscular dystrophy.

Adolescent↗