摘要:

ExtractThe growth of 39 children with Silver-Russell syndrome has been followed for 1—13 years. Pregnancy and labor were normal; none of the 61 sibs had the syndrome. Height at referral (mean age 4.6 years) averaged 3.6 SD below the mean and remained at this level during subsequent growth. Bone age averaged 69% of normal at referral but caught up by puberty, which occurred at the normal time. Nineteen cases were treated with human growth hormone without lasting effect. There is no clear-cut distinction between the Silver and Russell syndromes; the name should be Silver-Russell. It is likely that some 10% of cases have birth weights in the −1.5 to −2.0 SD range.SpeculationA detailed longitudinal study of the growth and development of children with the syndromes of Silver and Russell reveals a characteristic growth curve, very little affected by administration of growth hormone; a normal, not advanced, puberty; and a poor outcome.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractA comparative study of two smallpox vaccines, standard calf lymph vaccine, and an attenuated vaccine, CVI-78, was performed in 95 children. Primary vaccination with CVI-78 resulted in a more attenuated response than primary vaccination with standard vaccine. Sixty-one percent of those vaccinated with CVI-78 and 96% of those vaccinated with standard vaccine developed a major dermal reaction; 16% of those vaccinated with CVI-78 and 89% of those vaccinated with standard vaccine developed postvaccination neutralizing antibodies. Twenty-seven percent of the children vaccinated with CVI-78 demonstrated neither a dermal nor serologic postvaccination response, whereas only 2% of those vaccinated with standard vaccination demonstrated no postvaccination response.SpeculationSmallpox vaccine strain CVI-78 produces a modified local and serologic reaction in children. This vaccine may be overattenuated and thus is not useful as a replacement for standard vaccine. The vaccine in limited circumstances may be useful as a protective vaccine for those who might be expected to develop complications after challenge with standard vaccine. This speculation requires further study.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractRevaccination with standard calf lymph vaccine was performed on 26 children who had received a primary vaccination with an attenuated smallpox vaccine, CVI-78, and 22 children who had received primary vaccination with standard calf lymph. Revaccination resulted in a vesicular reaction in 96% of those who had been vaccinated previously with CVI-78 and 73% of those vaccinated previously with standard calf lymph. All children had a positive hemagglutination-inhibition (HI) antibody titer either after primary vaccination or revaccination. Only 65% of those initially vaccinated with CVI-78 vaccine had positive neutralizing antibodies after revaccination. All children who received primary vaccination with standard calf lymph had postrevaccination neutralizing antibodies. The children who had neither a dermal nor a serologic response after primary vaccination responded as primary vaccinees on challenge with standard calf lymph.SpeculationVaccination with CVI-78 alone offers only partial protection against variola and revaccination with standard calf lymph is necessary to offer full protection. The incomplete neutralizing antibody response in the CVI-78 group after revaccination with standard vaccine may indicate, however, that revaccination protection in this group is incomplete. Vaccination with CVI-78 also is not completely protective against the complications that could result from primary standard calf lymph vaccination since a significant percentage of those who received primary vaccination with CVI-78 had no postvaccination serologic or dermal response and responded like primary vaccinees when challenged with standard vaccine.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractLiver biopsy samples from the patients with hyperphenylalaninemia have an average of 5% of the normal hydroxylase activity. The parents of the patients have between 7.3% (excluding the value for one parent) and 10% of the normal hepatic hydroxylase activity. An explanation for these findings involves negative interallelic complementation, which involves protein-protein interaction between subunits in a multitneric enzyme. In support of this model is the evidence that rat liver phenylalanine hydroxylase is a multimeric protein composed of two electrophoretically distinguishable subunits.SpeculationThe finding that parents of patients with hyperphenylalaninemia have an average of 10% of the normal level of hepatic phenylalanine hydroxylase, a multimeric enzyme, can be explained on the assumption that the liver tissue of heterozygotes has an excess of enzyme molecules that contain at least one mutant subunit.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractWe have developed a standardized biophysical assay for the rapid detection of individuals homozygous or heterozygous for cystic fibrosis (C/F). The assay employs isoelectric focusing in thin layer polyacrylamide gels to analyze microliter quantities of whole serum for the presence of a C/F factor protein and for deletions in a group of proteins called proteins B, C, and D (Fig. 1). A pH 5–10 gradient is used (Fig. 2) and each sample is screened using a serum volume which contains 300μg immunoglobulin G (IgG). Individuals homozygous or heterozygous for C/F are distinguished from normal unaffected individuals on the basis of the presence of a C/F factor protein band (Table 1). Heterozygous carriers for C/F are distinguished from C/F homozygotes 75% of the time, on the basis of a deletion in either band B, C, or D (Table 2).On the basis of screening 65 patients with cystic fibrosis. 61 heterozygous carriers for C/F, and 105 normal control subjects, it was concluded that no obvious correlation existed between either sex, age, or severity of the disease in the individual C/F patient, and the absolute presence or absence of the C/F factor. In addition, no correlation existed between sex or age and the presence of the C/F factor or deletions in proteins B, C, and D in the individual heterozygous carrier for C/F or normal control subjects. Analysis of serum samples from 68 patients with a variety of other diseases, many with clinical symptoms resembling those seen in the patient with cystic fibrosis (Table 3), indicated that the C/F factor protein described in this study appears to be diagnostic for C/F genotypes, with the possible exception of patients with certain types of leukemia.SpeculationThe biophysical assay described in this report or a modification of it may prove to be a useful method for the routine detection of carriers of cystic fibrosis in the general population.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractMethylmalonyl-CoA carbonylmutase (mutase) activity was measured in fibroblast extracts from 15 patients with methylmalonic acidemia and in extracts of postmortem tissues from 6 of these children. Propionate oxidation and synthesis of 5′-deoxyadenosylcobalamin (AdoCbl, the vitamin B12coenzyme that is part of the mutase holoenzyme) were measured in intact fibroblasts. Mutase activity was low in the absence of added AdoCbl in fibroblast extracts from both control subjects and patients. When the assay included supplemental AdoCbl, mutase activity increased in the control subjects (to 24.0 pmol succinate/mg protein/mini and in extracts from eight of the patients (20.8 pmol/mg protein/min), but showed almost no change in extracts from the other seven patients (0.16 pmol/mg protein/min). We have defined the eight fibroblast lines that showed normal mutase activity in the presence of AdoCbl as “responsive lines” and the other seven lines as “nonresponsive.” In the liver or kidney extracts of postmortem tissues, mutase activity responded to AdoCbl supplementation if fibroblast mutase activity from that patient had responded, and failed to respond if fibroblast activity failed to respond. Mean propionate oxidation in intact fibroblasts was much higher in control lines than in either responsive or nonresponsive lines (0.728 vs 0.097 vs 0.080 nmol CO2/106cells/hr, respectively). AdoCbl synthesis was normal (0.27 pg AdoChl/mg cells wet weight) in nonresponsive fibroblasts but was undetectable (<0.005 pg/mg cells) in the responsive lines. Thus, the deficiency of mutase activity in responsive fibroblast lines is due to the failure to synthesize significant amounts of AdoCbl, whereas the deficiency in nonresponsive lines is due to some other abnormality, presumably a defect in the mutase apoenzyme.SpeculationFibroblasts can be used to define whether patients with methylmalonic acidemia have an error of vitamin B12metabolism if both mutase activity and AdoCbl synthesis are measured. The response of fibroblast mutase activity to the addition of AdoCbl reflects accurately the responsiveness of the enzyme in other tissues of the body. If an error of vitamin B12metabolism is diagnosed with cultured fibroblasts, a prolonged trial of vitamin B12therapy is warranted in the patient to seek evidence ofin vivoresponsiveness and clinical benefit from vitamin therapy.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractThe formation and specific activity of a catecholamine-binding brain protein were studied in mice exposed to perinatal malnutrition and neonatal infection.In the malnourished group, the total norepinephrine (NE)-binding protein was less than in the control group (malnourished 7.1 10.0 mg; control 13.0–14.0 mg), but the dopamine (DM)-binding protein was not significantly affected. In the infected group, the quantity of NE-binding protein was also decreased (infected 6.4–8.0 mg), but the DM-binding protein was higher than in the control group.The specific and total binding activity of [3H]NE to brain protein was greatly reduced in the infected group (infected 22.6 pmol/mg protein; control 88.4 pmol/mg protein), and decreased also in the guanidine-HCl eluate of the malnourished group (56.5 pmol/mg protein). The binding activity of [14C]DM was decreased markedly in the infected group (infected 131 pmol/mg protein; control 330 pmol/mg protein), but its specific binding activity was not as severely affected in the malnourished as in the infected group.The molecular weights of the catecholamine-binding protein were 75,000 in the control, 70,000 in the malnourished and 65,000 in the infected groups.There were no marked differences between the malnourished and control groups with regard to the amino acid composition of the NE-binding protein. The DM-binding protein in these animals had decreased amino acid content. The infected group exhibited remarkable changes in NE- and DM-binding brain protein.SpeculationCatecholamine-binding brain protein may be related to the specific protein in the storage granules in the formation of NEATP-protein complex, or it may be a part of a receptor molecule in postsynaptic cells. Perinatal malnutrition and neonatal infection may result in a derangement of catecholamine metabolism. The impaired formation of the synaptic connection may account for some of the functional changes of brain development.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractExperiments were designed to ascertain and compare the effects of acetyl salicylate and actinomycin D on RNA synthesis in mouse oocytesin vitroandin vivo. After exposure to the drugs the effects on RNA synthesis were measured by incorporation of [3H]uridine and autoradiography. The results indicate that acetyl salicylate inhibits RNA synthesis in the treated oocytes as does actinomycin D. The only difference in the effects of these two drugs is that salicylate inhibits RNA synthesis to a much lesser degree than does actinomycin D. Effects from a short exposure to salicylate may be reversible; the same effects with actinomycin D cannot be reversed.In uteroexposure of the female fetus may lead to partial or total sterility (depending on the dose and time of exposure) of that fetus and/or abnormal development of the progeny from those mice (F2).These results suggest that RNA synthesis in early oogenesis is a vital part of later development of the oocytes in adult mouse ovary. Inhibition of RNA may be one of the causes of malformations and sterility.SpeculationDuring early stages of development a species of RNA (known as masked messenger RNA) is synthesized by the oocyte nucleus and stored in the cytoplasm. After fertilization this RNA is utilized for the production of proteins necessary for the development of the embryo. If this RNA synthesis is inhibited by some agent (e.g., drugs) malformation or infertility could ensue in the female progeny.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractThe two pathways ofde novolecithin synthesis, choline incorporation (I) and phosphatidylethanolamine methylation (II), were examined in lung slices from rhesus monkey fetuses throughout the last half of gestation. Incorporation rates of pathway-specific radioactive precursors were used as a measure of lecithin production. At all stages of development studied, pathway I incorporated 10–50 times more precursor ([14C]choline) into lecithin than did pathway II ([14C]methionine or [14C]ethanolamine). In addition, although methylation activity did not change significantly during gestation, choline incorporation showed three distinct phases: (1) a stable, relatively low rate in early gestation, (3) an abrupt, twofold increase at approximately 90% of term, and (3) a return to lower activity levels in late gestation. This correlates with reports that lung lecithin concentration in fetal primates increases significantly in the last 10% of gestation.The lecithin to sphingomyelin (L/S) ratios measured in amniotic fluid samples obtained at abdominal delivery were compared with pathway activities in lung slices from the same fetuses. Significant correlation was found between the amniotic fluid L/S ratio and pathway I activity (r=0.77,P<0.001); in contrast, pathway II activity showed no relationship to the amniotic fluid L/S ratio. Thus, the L/S ratio appears to be a reflection of lung lecithin synthesis through the choline pathway.The conclusion that the choline pathway is the primary route ofde novolecithin synthesis in the nonhuman fetal primate lung is supported by three lines of evidence, (1) the predominance of choline incorporation into lecithin, (2) the late gestational rise in conversion of choline to lecithin, and (3) the correlation between pathway I activity and both lung lecithin concentration and amniotic fluid L/S ratio.SpeculationInadequate production of pulmonary lecithin via choline incorporation plays a primary role in the pathogenesis of respiratory distress syndrome (RDS). Future prenatal therapy to selectively increase pathway I activity in the fetal lung with minimal effects on other developing organs will require the definition of the normal intrauterine stimuli of the surge in lecithin synthesis via choline incorporation occurring at 90% of term gestation.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID