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Biomedical subjects

Y Koga

Publications and source records attributed to Y Koga.

At least 361 records · Page 20Linked to original sources

[Pulmonary complication following intra-arterial infusion of lipiodol-adriamycin emulsion for hepatocellular carcinoma, report of a case].

A case of acute pulmonary complication following intra-arterial infusion of Lipiodol-Adriamycin emulsion for hepatocellular carcinoma was reported. Intra-arterial infusion chemotherapy was performed on a 75-year-old male with Lipiodol-Adriamycin emulsion (Lipiodol 8 ml + Adriamycin 40 mg). Severe dyspnea and cyanosis started about 30 minutes after the infusion, and blood gas analysis revealed hypoxemia and hypocapnia. Chest X-ray revealed diffuse infiltrative shadow throughout the both lungs. He was on positive end-expiratory pressure breathing for 4 days. Clinical symptoms and chest X-ray improved rapidly in the course of two weeks, he became almost asymptomatic. We concluded that the nature of this pulmonary damage was pulmonary edema due to the large amount of Adriamycin that flowed into pulmonary artery via arterio-venous shunt present in the hepatocellular carcinoma.

Aged↗

Cytopathic effect determined by the amount of CD4 molecules in human cell lines expressing envelope glycoprotein of HIV.

A plasmid which has an envelope gene from the human T lymphotropic virus IIIB isolate of HIV under the transcriptional control of the human metallothionein IIA promoter was constructed and transfected into human CD4+ and CD4- cell lines. When the expression of the env gene was induced with metal ions in cloned cell lines from such transfected cells, the viral envelope protein precursor, gp160, was produced in both the CD4+ and CD4- cell clones in the same amounts. An extensive cytopathic effect developed resulting in cell killing; however, this occurred only in CD4+ and not in CD4- cell clones. The formation of syncytium was not found in those cells showing cytopathic effect. Immunofluorescence microscopy showed the envelope proteins localized in the periphery, forming a mass in the CD4+ cells but not in the CD4- cells after induction. Moreover, immunoprecipitation and immunoblot analyses demonstrated the formation of a complex between gp160 and CD4 molecules in the cytoplasm of those cells from whose surface CD4 Ag had already disappeared. Therefore, it is proposed that the formation of such a complex is directly related to the cell killing of CD4+ cells by envelope proteins in our cell clones as well as in infections with HIV.

CD4 Antigens↗

The relation between EEG and mental development following cardiac surgery performed under simple deep hypothermia in children.

In order to assess the accuracy of electroencephalography (EEG), in children who have undergone cardiac surgery under simple deep hypothermia, the relation between IQ or schoolwork achievement and the duration of circulatory arrest was investigated in 75 such children. Abnormal preoperative EEG's were found in 16 per cent of the children while abnormal postoperative EEG's were found in 17 per cent. The children were divided into 4 groups, according to pre- and postoperative EEG results. Schoolwork achievement scores ranged between 3.0 and 3.2, the difference among the groups being insignificant. Moreover, no significant shift in IQ was found among the groups. Finally, regarding the number of children who were able to go on to a higher level of education, including high school then college or university, again no significant differences were found among the 4 groups. In a comparison with the number of such children in neighboring Nagasaki prefecture able to continue on to a higher level of education, no significant differences were seen either. The findings and statistics of this investigation therefore indicate that pre- and postoperative EEG's are not always a reliable reference for assessing the prognosis of cerebral activity.

Achievement↗

Prenatal diagnosis of fetal intracranial calcifications.

A case is presented wherein fetal intracranial calcifications as a result of intrauterine cytomegalovirus infection were visualized by computed tomography and magnetic resonance imaging at 36 weeks' gestation. Diagnosis of in utero cytomegalovirus infection was made by isolation of the virus from amniotic fluid. No symptomatic abnormality has been noted in the neonatal period except periventricular calcifications.

Adult↗

Chronic progressive external ophthalmoplegia: a correlative study of mitochondrial DNA deletions and their phenotypic expression in muscle biopsies.

Deleted mitochondrial DNA (mtDNA) has been shown to coexist with normal mtDNA (heteroplasmy) in muscles from chronic progressive external ophthalmoplegia, including Kearns-Sayre syndrome. In this study, we correlated heteroplasmic mtDNA abnormality with clinical, biochemical and histological findings with the following results: (1) large deletions ranging from 1.8 to 8.8 kb in 22 muscle specimens from 28 patients who had ophthalmoplegia clinically and focal cytochrome c oxidase (CCO) deficiency by histochemistry, (2) no difference in clinical and biochemical findings between patients with and without mtDNA deletions, (3) no relationship between the size, site or populations of deleted mtDNA and respiratory chain enzyme activities in muscles, (4) positive correlation between the number of CCO-deficient fibers and the populations of deleted mtDNA, and (5) higher incidence of CCO-negative fibers in patients with deleted mtDNA than in those with no deletion of mtDNA. These results suggest that deleted mtDNA is, at least in part, responsible for focal CCO deficiency as a phenotypic expression and that the investigation on pathogenetic mechanism of focal CCO deficiency may provide a clue to understanding the underlying pathophysiology in this disorder.

Chromosome Deletion↗

Progressive cytochrome c oxidase deficiency in a case of Leigh's encephalomyelopathy.

We report the morphological, biochemical, immunological, and genetic findings in a patient with the clinical characteristics of Leigh's disease due to multisystemic cytochrome c oxidase (CCO) deficiency. Muscle biopsy at 2 years and 5 months of age showed markedly decreased CCO and cytochrome a + a3, moderately decreased NADH-cytochrome c reductase to 46.3%, and generalized loss of immunologically detectable CCO subunits, but other respiratory chain enzyme proteins were normal. All the tissues examined at autopsy showed decreased activity of all respiratory chain enzymes except complex II. The decrease in cytochromes b and a + a3 were in harmony with decreased enzyme activities in complex III and IV (CCO), respectively. All immunologically detectable subunits of CCO in immunoprecipitation were uniformly decreased in the cardiac and skeletal muscles, but subunits 1 and 4 were selectively decreased in other organs except liver. No large deletion could be detected in the cardiac muscle mtDNA after digestion with restriction enzymes. These results suggest that the respiratory chain enzymes are variable in their activity and the amount of enzyme proteins decreases as the disease progresses.

Brain↗

[11C]octopamine synthesis using [11C]cyanide: chemical and enzymatic approaches for the [11C]cyanohydrin synthesis.

[11C]-p- and m-octopamine hydrochloride were synthesized from [11C]HCN in a two-step sequence. Chemical and enzymatic approaches were used for the formation of the [11C]cyanohydrin intermediates as the key step. Isolated radiochemical yields of 0.7-2.3% at the end-of-synthesis were obtained with an overall preparation time of 40-60 min. The enantiomeric purity of the [11C]-p-octopamine obtained through the enzymatic process was 92% e.e. in the (S)-enantiomer, whereas that of the [11C]-m-octopamine was 42% e.e. in the (R)-enantiomer, as determined by HPLC without any derivatization.

Carbon Radioisotopes↗

Effect of prolonged hypothermic ischaemia on myocardial sarcoplasmic reticular calcium transport.

STUDY OBJECTIVE: The aim of the study was to assess the effects of hypothermia on sarcoplasmic reticulum in myocardium subjected to prolonged ischaemia. DESIGN: Calcium regulatory activity of myocardial sarcoplasmic reticulum was measured in hearts subjected to various periods of hypothermic ischaemia in comparison with hearts subjected to normothermic ischaemia. SUBJECTS: Hearts (n = 5-9 per experiment) were obtained from male New Zealand white rabbits, 2.0-2.8 kg weight. MEASUREMENTS AND RESULTS: Calcium uptake and calcium dependent ATPase activity were measured in isolated sarcoplasmic reticulum vesicles after hypothermic ischaemia was produced by immersing hearts in saline at 4 degrees C for 3, 6, or 12 h. Normothermic hearts were immersed for 3 h at 37 degrees C. Calcium uptake and calcium dependent ATPase (Ca-ATPase) activity were markedly inhibited by normothermic ischaemia. In hypothermic ischaemia, calcium uptake was only slightly depressed after 3 h, though longer periods of ischaemia resulted in significant depression of uptake. Ca-ATPase activity was unaffected after 6 h of hypothermic ischaemia. The ratio of calcium uptake to Ca-ATPase activity decreased after 3 h of hypothermic ischaemia. The phosphoenzyme concentration in sarcoplasmic reticulum was unaffected up to 6 h. The ratio of Ca-ATPase activity to phosphoenzyme concentration was not significantly altered until 12 h. Protein composition, examined by SDS-polyacrylamide gel electrophoresis, showed a decrease in 100,000 dalton polypeptide in normothermic ischaemia and after 12 h of hypothermic ischaemia. CONCLUSIONS: These results suggest that the depression of calcium uptake activity after 6 h of hypothermic ischaemia is likely to be due to uncoupling of calcium transport from ATP hydrolysis. Depressed Ca-ATPase activity at 12 h can be attributed to a reduction in the number of active calcium pump units. Hypothermia preserves function of myocardial sarcoplasmic reticulum during ischaemia for up to 3 h.

Animals↗

Continuous wave Doppler echocardiographic evaluation of St. Jude prosthetic mitral valves in children.

The function of 9 St. Jude prosthetic mitral valves in 8 children was evaluated by continuous wave Doppler (CWD) echocardiography 28 +/- 22 months after implantation. All valves were apparently functioning normally on clinical examination. Peak flow velocity, mean flow velocity, pressure half-time and mean pressure gradient were determined from the transmitral flow velocity curve by CWD echocardiography. For comparison, the same parameters were examined in 15 normal children and 14 adults who had undergone mitral valve replacement. All measured values were greater in adults and children who had undergone valve replacement than in normal children. There were no differences in any parameter in adults or children in whom prostheses 25 mm or larger had been implanted. Although 3 children in whom prostheses 23 mm or smaller had been implanted had greater values for each parameter than those who received 25 mm or larger prostheses, there were no symptoms or signs of mitral stenosis. These data may be useful as guidelines for normal Doppler characteristics for St. Jude mitral valves in children. In an asymptomatic child whose prosthetic valve developed obstruction by granulation tissue overgrowth, each parameter significantly worsened as the heart rate increased. The changes in these parameters in 2 normally functioning St. Jude valves during atrial pacing were insignificant. The fluctuation of Doppler characteristics with changes in heart rate is useful for differentiating normally functioning prosthetic valves from impending stenosis.

Adolescent↗

Intracellular distribution of the envelope glycoprotein of human immunodeficiency virus and its role in the production of cytopathic effect in CD4+ and CD4- human cell lines.

Human CD4+ and CD4- monocytoid cell lines were transfected with a constructed plasmid that has the envelope gene of human immunodeficiency virus under the transcriptional control of human metallothionein IIA promoter; the transfected cells were then cloned. These CD4+ and CD4- transfectant cell clones, both of which expressed almost the same amount of gp160 after induction with metal ions, were used for ultrastructural analysis of the distribution of the envelope glycoprotein in the cytoplasm. Immunofluorescence microscopy with an anti-envelope glycoprotein monoclonal antibody showed localized distribution of gp160 in the CD4+ cell clone and diffuse distribution of gp160 in the CD4- cell clone. These observations were substantiated by immunoelectron microscopy, in which the aggregated form of gp160 was observed in the cytoplasm of CD4+ cells but was scarce in that of CD4- cells. A notable finding was that the sites corresponding to the nuclear pores were occupied with aggregates of gp160 in CD4+ cells, exhibiting cytopathic effects. Both freeze-fracture and transmission electron microscopy also showed abnormal morphology around the nuclear pores and perinuclear space. These results support the possibility that such gp160 complexes accumulated around the nuclear pores primarily disturb the transportation of many molecules between the nucleus and the cytoplasm, resulting in a cytopathic effect in the CD4+ cell clone.

CD4 Antigens↗

Physical training in patients with valvular heart disease after surgery.

The necessity, the methodology and clinical benefit of physical training were evaluated in 85 patients with valvular heart surgery. In 21 patients who had undergone the exercise stress test before surgery, corrective valvular surgery increased maximal oxygen uptake (max.VO2) from 15.4 before to 18.9 ml/min/kg, while 11 (52%) of them failed to increase exercise capacity over 5 METs. Of the total 85 patients, 41 (58%) again showed reduced exercise capacity in the initial postoperative stress test, suggesting that a return to work might be difficult without rehabilitation in these patients. We then compared two training programs: program A of short duration and frequent exercise and program B of longer duration and less frequent exercise, both using a bicycle exercise set at an intensity of 70% of the max.VO2. Both programs similarly increased max.VO2, while patients preferred program A, suggesting that exercise of longer duration could not be tolerated because of deconditioning. Program A was then prescribed to 62 patients, and it increased max.VO2 from 18.2 to 20.7 ml/min/kg after 4 weeks training without any complication. In 9 patients who served as controls undergoing no physical training, no spontaneous improvement in exercise capacity was observed. Of the 76 patients who received either program A or B, 28 patients failed to increase the max.VO2 by 10% or more. These patients presented atrial fibrillation, a cardiothoracic ratio greater than or equal to 60% or exercise-induced ST depression more frequently, suggesting that residual cardiac dysfunction might inhibit the training effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship between coronary risk factor and arteriographic feature of coronary atherosclerosis.

Coronary arteriography was performed in 1,029 consecutive patients with ischemic heart disease and the relationship between the arteriographic features of coronary atherosclerosis and coronary risk factors was analyzed by case control studies. Patients were divided into four groups according to coronary arteriographic findings. Patients with normal or near normal coronary arteriograms (Group I) showed a high prevalence of smoking habit and a higher value of serum uric acid compared with the control group, so smoking and hyperuricemia were considered to be the risk factors for coronary atherosclerosis in patients of group. Four selected variables: smoking, hyperuricemia, hypertension and hyperlipidemia, were identified to be risk factors for the patients with minor plaques in the coronary arteries (Group II). As in Group I, smoking and hyperuricemia had a close relationship to solitary tight plaque in a branch of the coronary artery (Group III). Multiple tight stenoses in the coronary arteries (Group IV) correlated closely with smoking, hyperuricemia, hypertension, hyperlipidemia and diabetes mellitus. Thus, there were many strong risk factors for patients with diffuse, extended coronary atherosclerosis (Group II and Group IV), while only two factors, smoking and hyperuricemia, were considered to be risk factors for the patients with near normal coronary arteries ies or a solitary plaque in a branch of the coronary artery. These findings suggest that the role of the coronary risk factors on the pathogenesis of coronary atherosclerosis is not uniform but variable depending on the morphologic variability of the coronary atherosclerosis and on the pathophysiology of the ischemic heart disease.

Adult↗

Increased cardiovascular responses to norepinephrine in patients with hypertrophic cardiomyopathy.

Sympathetic nerve-adrenergic receptor systems have been implicated in the pathogenesis of hypertrophic cardiomyopathy (HCM). We studied plasma norepinephrine (NE) levels during exercise and cardiovascular responses to NE in 26 patients with nonobstructive HCM and 26 age- and sex-matched controls. There were no differences in the plasma NE levels at rest (201 +/- 84 vs 233 +/- 100 pg/ml) or in the slope of the log NE-heart rate relationship during exercise between the HCM patient and control groups. When NE was infused intravenously, with increasing doses to 0.20 microgram/kg/min, HCM patients displayed significantly greater increases in mean blood pressure (29 +/- 7 vs 14 +/- 5%, p less than 0.001) and peripheral vascular resistance (39 +/- 7 vs 26 +/- 7%, p less than 0.001) than controls. Although the fractional shortening decreased during NE infusion in controls, it was unaffected in HCM patients, despite a greater elevation of systolic pressure. The responses of left ventricular contractility, estimated by a ratio of systolic blood pressure to end-systolic dimension, were significantly greater in patients with HCM (31 +/- 7 vs 13 +/- 6%, p less than 0.001). These observations indicate that vasoconstrictive responses of the peripheral arteries and inotropic responses of the left ventricular muscle to NE were augmented in patients with HCM, while sympathetic nervous activity remained unchanged. Accordingly, we propose that increased activity of the cardiovascular adrenergic receptor systems, rather than enhanced sympathetic nervous function, may be related to the development of abnormal hypertrophy in HCM.

Adult↗

The effects of pacing-induced left bundle branch block on left ventricular systolic and diastolic performances.

To assess the effects of pacing-induced left bundle branch block on left ventricular (LV) systolic and diastolic performance, we performed digital subtraction ventriculography while simultaneously measuring LV pressure with a catheter tip micromanometer. The subjects included 10 patients with a sinus rhythm, a normal QRS duration and PR interval within 0.22 sec. LV performance was assessed during both right atrial pacing (AP) and atrioventricular sequential pacing (AVP) at the same pacing rate. The atrioventricular pacing interval during AVP was adjusted to be the maximal interval that showed the QRS configuration seen during complete right ventricular pacing. LV end-diastolic pressure and volume during AVP did not differ from those during AP. Peak positive and negative dp/dt during AVP were significantly lower than those during AP. Time constants were also significantly longer during AVP. The QRS duration during AVP significantly correlated with end-systolic volume and time constants, and inversely correlated with ejection fraction and +dp/dt. These observations indicated that conduction disturbance per se, induced by AVP, could not only impair LV systolic performance but also diastolic performance, possibly due to asynchronous contraction and relaxation of the left ventricle.

Adult↗