Antley-Bixler syndrome in a sister and brother.
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Biomedical subjects
Publications and source records attributed to Y Wada.
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Muscle biopsy specimens from two patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) were studied biochemically. 14CO2 production rates from (1-14C)pyruvate, (U-14C)malate, and (1-14C)2-ketoglutarate were all decreased in intact mitochondria in both patients. Rotenone-sensitive NADH cytochrome c reductase activities were decreased to 8% (patient 1) and 6% (patient 2) of control values; succinate cytochrome c reductase and cytochrome c oxidase values were within normal limits. These results indicate that both patients have a defect of NADH-CoQ reductase of the respiratory chain and that MELAS can be brought about by a defect of NADH-CoQ reductase.
Eighty-six asphyxiated full-term neonates with CNS complications such as hypoxic-ischemic encephalopathy, admitted during a 10-year period (1972-81), were studied. Sixty-three (73%) of the infants survived the neonatal period, and 55 of these, excluding one who died at 7 months, were followed for 3 to 13 years. Thirteen (24%) of these 55 children showed either major (n = 8) or minor (n = 5) abnormalities. The former had multiple significant handicaps such as cerebral palsy, epilepsy and mental retardation. The latter had mild sequelae that did not interfere with normal life. High risk factors of predictive value in infancy for the sequelae were the absence of the Moro reflex over 6 days and abnormal neurological signs on discharge (P less than 0.001, respectively). Although the neonatal mortality decreased slightly in the last four years (1978-81) compared to in the first and second three year periods (1972-74, 1975-77) (P less than 0.10), the unchanged pattern of the outcome over the 10 years might indicate the importance of more preventive and intensive care for perinatal asphyxia to reduce the incidence of handicapped children.
In a double-blind, 4 week study, 42 chronic schizophrenic inpatients receiving antipsychotic and antiparkinsonian (AP) drugs for greater than 3 months were either switched to placebo or maintained on biperiden. In the majority of the patients no clinically apparent discomfort was observed, and only two of 21 placebo patients developed extrapyramidal side effects (EPS) severe enough to require resumption of AP therapy. No significant increase was shown in most items on EPS. Our data suggest that for the majority of patients on long-term AP medication AP drugs should be prescribed only when EPS develop.
Two sibs, a 13-year-old girl and an 11-year-old girl, with typical clinical features of the Prader-Willi syndrome (PWS) are reported. High-resolution chromosome analysis showed the normal karyotype in the elder sister, and 46,X,del(X)(pter----q26.1:) in the younger sister. But an interstitial deletion of 15q was not detected in either of the cases. PWS is most probably an etiologically heterogeneous syndrome consisting of two subgroups, with partial deletion and non-deletion of chromosome 15, respectively.
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Growth charts for head circumference in Japanese children from birth to fifteen years of age are presented. The charts were compiled from the pooled data obtained in a prospective longitudinal study on development and growth in Nagoya city. An adolescent growth spurt in head circumference was found and this spurt occurred earlier in girls than in boys. Heads were smaller up to the age of 10 years and larger beyond that age than those in Nellhaus' composite charts. The heads of children of both sexes in our study are definitely smaller than those of children born in the United Kingdom in the same period, but they are considerably larger than those of children born in Japan more than 50 years ago. Therefore, the standards for head circumference will differ from country to country and from generation to generation.
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The mechanism of hyper-reactivity of the Dextrostix system when contaminated with alcoholic skin cleaning agents was investigated. When sodium fluoride was supplied to block glucose oxidase activity and hydrogen peroxide was exogenously provided benzidine peroxidation could be preferentially studied. Benzidine hydrochloride was the most likely site of the hyper-reaction.
An abnormal hemoglobin was found by isoelectric focusing in the blood of a Finnish woman with erythrocytosis. Oxygen equilibrium curves of the patient's hemolysate indicated the presence of a variant with a very high oxygen affinity. Structural analysis was carried out by mass spectrometry. In the spectrum of the tryptic digest, an abnormal peptide was found at m/z1278 which corresponded to the mass number of the protonated molecular ion of beta T4 with 36Pro----Thr substitution. The structure was confirmed by the mass spectrum of the chymotryptic digest.
Using dried blood on filter paper, neonatal screening and mass-spectrometric analysis of hemoglobin variants were carried out in Osaka Prefecture, Japan. The following results emerged. (1) Of 140,597 newborns screened, 28 alpha (1/5,000) and 91 gamma (1/1,500) chain variants were detected. (2) Of 65 gamma chain variants examined, more than half (in 40 samples) were Hb F Yamaguchi (A gamma T 80 Asp----Asn). This fact explains the high incidence of gamma chain variants in the present study. (3) Two new gamma chain variants, Hb F Fuchu (G gamma 21 Glu----Gln) and Hb F Minoo (G gamma 72 Gly----Arg), were detected.
Poststenotic blood flow velocities were evaluated in nine patients with 75% to 99% stenosis of the left anterior descending coronary artery (LAD) during coronary artery bypass graft surgery. We used the 20 MHz 80-channel pulsed Doppler velocimeter developed in our laboratory. An operator placed a specially designed probe on the native LAD with his fingers. Before induction of extracorporeal circulation, LAD blood velocities were measured at several locations distal to the stenosis. The poststenotic flow velocities were rich in systolic flow component with reduced diastolic component. The velocity configuration in the poststenotic portions was characterized by the presence of reverse flow velocities and/or irregularity of the velocity pattern near the vessel wall, indicating the existence of flow separation and recirculation in the regions. The broadening of the velocity spectrum observed at central axial regions suggested the occurrence of flow disturbances. After grafting, the velocity waveform in the LAD beyond a vein bypass graft changed to a diastolic-predominant pattern with a relatively small systolic component. A transient bypass graft occlusion caused a marked reduction in diastolic flow velocity. The systolic-to-diastolic velocity ratio increased from 0.27 +/- 0.07 to 1.50 +/- 0.50 (p less than .01) by the graft occlusion.
A novel, small-scale method was developed for detecting carriers of a prealbumin variant associated with type 1 familial amyloidotic polyneuropathy (FAP). Prealbumin isolated from plasma by a two-step preliminary chromatographic procedure was further separated into two peaks by reverse-phase high-performance liquid chromatography. The normal and variant prealbumins were identified by secondary ion mass spectrometry. The procedure is relatively simple, reliable, and applicable to the definitive diagnosis of FAP in affected patients and also as a preclinical test for the offspring of patients with FAP.
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A 2 month-old Japanese girl with hereditary orotic aciduria type I was treated with oral uridine supplement. The activities of orotate phosphoribosyltransferase (OPRT) and orotidine-5'-phosphate decarboxylase (ODC) in erythrocytes were 2.7 and 0.4%, respectively, of those in the controls. Megaloblastic anemia, excessive urinary excretion of orotic acid, lymphopenia and decreased number of OKT3 positive lymphocytes on admission were corrected after the uridine supplement. Peripheral blood lymphocytes (PBL) were cultured for 24 hr in RPMI 1640 medium with 10% heat-inactivated fetal calf serum and further stimulated with PHA-P, ConA or PWM in the presence of 10 to 1000 microM uridine. EB virus-transformed B cell line (LCL) maintained with an optimal concentration of uridine was cultured for 48 hr in uridine free medium and cultured for an additional 48 hr with 1 to 1000 microM uridine. The incorporations of leucine in to PHA-, ConA- and PWM-stimulated PBL and into LCL of the patient increased in the presence of uridine over 10 microM, although they did not increase in controls. These data suggest that low protein synthesis might correlate with an immune deficiency in hereditary orotic aciduria type I.
The structures of six inhibitors of prolyl hydroxylase, fibrostatins A, B, C, D, E and F produced by a strain of Streptomyces, were deduced to be 1, 2, 3, 4, 5 and 6, respectively, from chemical and spectroscopic evidence, especially from extensive 13C NMR studies including selective decoupling and low power selective decoupling experiments monitored by 13C-1H long-range couplings. These compounds are the first naturally occurring 2,6,7- or 3,6,7-tri-substituted or 2,3,6,7-tetra-substituted 5-hydroxy-1,4-naphthoquinone inhibitors possessing N-acetyl-L-cystein-S-yl moieties in the molecule.
Although the human tumor clonogenic assay (HTCA) is extremely reliable in determining clinical correlations, it is a complicated process requiring considerable time in order to obtain results. Thus, an experimental study on cytopathologic observation (cytologic assay) and comparative evaluation between it and HTCA were performed in order to establish a more rapid and accurate drug sensitivity test. Materials included Colon 26, a cell line established in our department, malignant effusion and surgical specimens. In carrying out HTCA according to the Hamburger-Salmon method, the cell suspension samples following exposure to anti-tumor agents (MMC, L-PAM, ADM, CDDP) were cultivated in test tubes for 3-8 hours and stained by the Papanicolaou and Giemsa methods. According to Tokita's criteria, when cellular changes showed as nuclear pyknosis and nuclear destruction were found to have increased significantly in comparison with a control group, the cells were judged to be sensitive. Very similar and parallel results were obtained between HTCA and cytologic assay in this study, with a significant correlation. Cytologic assay was proved to be an easy, rapid and accurate method for testing drug sensitivity and its clinical application can be expected in the future.