Biomedical subjects
Publications and source records attributed to G Takada.
In conclusion, the NPFR value did not change during the early neonatal period. The fact that this index does not change suggests that it might be useful as a parameter for diastolic filling, assuming that there is no significant diastolic filling change in the left ventricle over this time frame.
The purpose of this study was to see the relationship between changes in pulmonary venous flow velocities and those in transmitral flow velocities during the first day of life. A serial Doppler echocardiography was performed in 24 normal neonates at 2, 12, and 24 hours of age. The size of the ductus arteriosus was 4.3 +/- 0.5 mm at 2 hours and 2.1 +/- 0.7 mm at 12 hours, and closed in 21 of 24 neonates at 24 hours. The peak systolic pulmonary venous flow (peak S), peak diastolic pulmonary venous flow (peak D), peak D/S, peak velocity at early diastolic filling (peak E), and peak E/A, which were high at 2 hours, decreased significantly at 12 hours but remained constant thereafter. The size of the ductus arteriosus was found to be correlated with peak S, peak D, and peak D/S. There was a direct correlation between peaks E and D (r: 0.64, p < 0.01) as well as a direct correlation between peaks E/A and D/S (r: 0.36, p < 0.05). These results indicate that the diastolic pulmonary venous flow is determined by the same factors that influence the transmitral flow. These waveforms may reflect the increase in pulmonary circulatory volume by left-to-right shunting through the ductus arteriosus.
Congenital hypomyelination neuropathy (Lyon type) is characterized by a non-progressive clinical course and a histopathological formation of atypical onion-bulb. We have studied the immunohistochemical expression of the major peripheral myelin proteins including P0 protein, myelin basic protein (MBP) and P2 protein in three such patients. No significant difference was observed between the patients and the controls, as to the P0 and MBP staining. In contrast, P2 protein antiserum scarcely stained the patients' nerve fibers except for a few scattered adequately myelinated fibers. Assuming the pathogenetic contribution of the extremely decreased P2 protein to the disease, we investigated P2 protein gene by sequencing all coding regions but failed to detect any change in the nucleotide sequence. Further investigation including the analysis of promoter region of P2 protein gene is needed to elucidate the mechanism of congenital hypomyelination neuropathy.
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To determine hepatic diseases in obese children, biochemically and histologically, 11 obese patients with abnormal serum transaminase activities were subjected to this study. Fat accumulation in the liver was semiquantitatively graded, and histologically the 11 patients were classified into four groups; fatty liver, fatty hepatitis, fatty fibrosis and fatty cirrhosis. All patients had fat deposition in liver specimens, the grade of which did not significantly correlate with the degree of obesity. The grade of fat deposition in the liver specimens also did not significantly correlate with either serum transaminase activities or GOT/GPT ratio. Five patients were grouped into the fatty liver group, three into the fatty hepatitis group, and the remaining three patients into the fatty fibrosis group. However, no significant differences were found among the three histologically classified groups in terms of serum transaminase activities or GOT/GPT ratio. The usefulness of serum transaminase activities and GOT/GPT ratio was limited in predicting the severity of fat deposition or histological abnormality in pediatric obese patients.
A 10 year old girl with hypertrophic cardiomyopathy (HCM) developed high grade atrioventricular (A-V) block unexpectedly, which instantly led to syncope; she required a permanent pacemaker. High grade A-V block, a rare complication of HCM, relates closely to syncope or sudden death in this disease and if progressive the use of cardiac pacing should be considered without delay.
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To investigate the changes in regional wall motion of the left ventricle in the early neonatal period, serial echocardiography was performed in normal neonates at 2 and 120 hr after birth. Quantitative analysis of the regional wall motion was performed by the centerline method. We measured right ventricular systolic time intervals, left ventricular stroke volume, flow velocity-time integral of the pulmonary artery, and size of the ductus arteriosus. The ductus arteriosus was 4.5 +/- 0.5 mm at 2 hr but was closed in all subjects by 120 hr. At 2 hr, there was hyperkinesis of the interventricular septum which disappeared by 120 hr. The right ventricular systolic time intervals at 2 hr showed a sign of pulmonary hypertension. At 2 hr, the left ventricular stroke volume was at the highest level and the flow velocity-time intervals of pulmonary artery was at the lowest level. Thus the hyperkinesis of the interventricular septum at 2 hr might reflect the circulatory changes that are characteristic of the early neonatal period.
Types A and B Niemann-Pick disease (NPD), an autosomal recessive lysosomal storage disorder, are caused by deficiency of acid sphingomyelinase (ASM). The recent identification of mutations in ASM gene causing types A and B NPD has led to the investigation of the phenotypic heterogeneity and the ethnic distribution of this disease, especially in Ashkenazi Jewish population. To characterize the mutations causing NPD in Japanese population, we analyzed the genomic sequence of ASM from a Japanese patient with type A NPD by PCR amplification and sequencing. A new mutation, Y446C, was identified. The authenticity of this lesion was demonstrated by the expression of the Y446C allele in COS-1 cells. No residual ASM activity was detected from the expression of the Y446C.
A case of an infant with a rare combination of polysplenia syndrome with common atrioventricular canal and persistent truncus arteriosus is presented. In our present case, severe common atrioventricular valve regurgitation was identified, as in previous cases. To our knowledge, echocardiographic and autopsy findings of this association has not been previously reported. The persistent truncus arteriosus is extremely rare in the setting of the polysplenia syndrome, but the present case report demonstrates that these anomalies may, at times, occur.
X-linked liver glycogenosis (XLG) due to liver phosphorylase kinase (PHK) deficiency is the most frequent liver glycogen storage disease. The affected patients present in early childhood with hepatomegaly and growth retardation. We isolated and determined the structure of human liver alpha subunit of PHK (PHKA2) cDNA. The 3705 base pair open reading frame encodes a polypeptide of 1235 amino acid residues, and the deduced amino acid sequence shows 93 and 68% homology to that of rabbit liver alpha subunit of PHK and human muscle alpha subunit of PHK, respectively. We identified a missense mutation, a valine substitution for glycine at amino acid 193, in the PHKA2 gene of a family with XLG.
The history and bases of enzyme replacement therapy are briefly reviewed. The enzyme replacement therapy for Gaucher disease type 1, which has been developed for clinical use and is about to be introduced in our country, was described somewhat in detail under the items of the modification of human placental glucocerebrosidase into the macrophage-terminated enzyme, its clinical usage, effects and their evaluations, adverse effects, and new attempts of its application for Gaucher disease types II and III, now being under clinical trials. Also touched are developments of other enzymes for such lysosomal diseases as Fabry disease, Pompe disease, Hurler syndrome, Hunter disease, and Sly disease.
To evaluate the effect of changes in preload on left ventricular (LV) performance, we used echocardiography to measure end-diastolic dimension, end-systolic dimension, and stroke volume in newborns at 2, 12, 24, and 120 h of age. The stroke volume was calculated by the pulsed Doppler technique. The stroke volume showed the highest level at 2 h of age. The size of the ductus arteriosus correlated with the stroke volume. These results indicated that the increase in stroke volume was related to the increase in LV preload due to the shunt flow volume through the patent ductus arteriosus. M-mode echocardiographic indexes such as end-diastolic dimension, LV end-diastolic volume, and LV ejection fraction did not show any significant changes from 2 to 120 h of age. We conclude that M-mode echocardiographic evaluation of LV performance is unreliable in the early neonatal period. Our data also provide a useful basis for the interpretation of abnormal left ventricular systolic function in the early neonatal period.
The gene for human aminomethyltransferase (AMT), also known as the T-protein of the glycine cleavage system, was isolated from a human placental cosmid library and examined by restriction mapping, polymerase chain reaction analysis, and DNA sequencing. The gene is about 6 kb in length and consists of nine exons. The 5'-flanking region of the gene lacks typical TATAA sequence but has a single defined transcription initiation site detected by the primer extension method. Two putative glucocorticoid-responsive elements and a putative thyroid hormone-responsive element are present. The AMT gene was assigned to subband 3p21.2-p21.1 by fluorescence in situ hybridization.
We have investigated the molecular lesions of T-protein deficiency causing typical or atypical nonketotic hyperglycinemia (NKH) in two unrelated pedigrees. A patient with typical NKH was identified as being homozygous for a missense mutation in the T-protein gene, a G-to-A transition leading to a Gly-to-Asp substitution at amino acid 269 (G269D). Sibling patients of a second family with atypical NKH had two different missense mutations in the T-protein gene (compound heterozygote), a G-to-A transition leading to a Gly-to-Arg substitution at amino acid 47 (G47R) in one allele, and a G-to-A transition leading to an Arg-to-His substitution at amino acid 320 (R320H) in the other allele. Gly 269 is conserved in T-proteins of various species, even in E. coli, whereas Gly 47 and Arg 320 are replaced by Ala and Leu, respectively, in E. coli. The mutation occurring in more conservative amino acid residues thus results in more deleterious damage to the T-protein, and gives the severe clinical phenotype, viz., typical NKH.
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In four patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) in which mutated mitochondrial deoxyribonucleic acid was seen, hypertrophic cardiomyopathy and angiopathy was demonstrated by echocardiography, dipyridamole stress scintigraphy, and cardiac catheterization. On stress scintigraphy with dipyridamole, three patients showed hypoperfusion in the early image and a "filling-in" pattern in the late image. However, coronary angiography did not demonstrate narrowing of the large vessels in these patients. Light and electron microscopy of endomyocardial biopsy specimens indicated abnormal mitochondria, with marked increase in the number and size of mitochondria in endothelium. Modified Gomori's trichrome staining in biopsied endomyocardial specimens revealed a red-purple deposit similar in appearance of the ragged-red fibers in skeletal muscle, a characteristic finding of mitochondrial disease. Deterioration of complex I in the mitochondrial electron transfer system, which is widely observed in various mitochondrial diseases, appeared in biopsied skeletal muscle of our patients, indicating deficiency of some subunits of complex I. These results indicate that mitochondrial diseases such as MELAS show not only cardiomyopathy but also angiopathy. We speculate that proliferation of mitochondria leads to narrowing of the lumen of arterioles, which might be responsible for the ischemic findings observed scintigraphically.
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