摘要:

ExtractThe IQ's of Jamaican boys aged 6–10 were associated significantly with the presence or absence of severe malnutrition in infancy, with height at time of IQ testing, and with a measure of the boys' social background. A multiple correlation coefficient of 0.674 was obtained between IQ and the three factors. Social background contributed 0.294 of the variance, height 0.112, and severe malnutrition 0.049. The two extreme groups of boys,i.e.,those malnourrished, small at follow-up, and with unfavorable social backgrounds and those not malnourished, tall at follow-up, and with favorable social backgrounds had average IQ's of 49.4 and 74.9, respectively (from Table 5). Only two of the boys in the most advantaged group had IQ scores that overlapped with the most disadvantaged group. Boys with severe malnutrition in infancy, but who are tall at follow-up and have a favorable social background have an average IQ 11 points higher than boys who did not experience severe malnutrition, but who are short at followup and have a unfavorable social background. The difference in IQ between boys who did and did not experience severe malnutrition in infancy varies under different conditions of height and social background when those are held constant for both groups. Under the most favorable conditions of being tall and having an advantageous social history the average IQ of the malnourished boys is only 2 points lower than those not malnourished. Under the most unfavorable conditions of short stature and a disadvantageous social background the IQ of the malnourished boys is 9 points lower than those not malnourished (Table 6 and Fig. 1).SpeculationThe long range consequences of a severe episode of malnutrition in infancy can be understood only in the context of the human ecologic conditions including social, economic, and biologic factors which the child and his family have experienced during their lifetimes. Results of the present study suggest that an episode of severe malnutrition in infancy in the context of a lifetime of generally favorable experiences for child development does not appear to cause any intellectual impairment, but when severe malnutrition occurs in an ecology generally unfavorable for intellectual development, the early malnutrition has a clear relation to later intellectual impairment.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractAn infant suffering from metabolic acidosis attributable to hyperlactatemia (6.1 mmol/liter) accompanied by hyperalaninemia (1 mmol/liter) and hyperserinemia (0.6 mmol/liter) is described. The urinary excretion of lactate and pyruvate was greatly elevated; the lactate to pyruvate ratio was normal. The urine showed low levels of citrate, isocitrate, and cis-aconitate, and low or normal levels of α-oxoglutarale, succinate, malate, and methylmalonate. Aspartate was slightly elevated in serum and urine, indicating a corresponding increase of its α-ketoacid oxaloacetate. These patterns of organic acids and amino acids suggested anin vivodefect in the oxidation of pyruvate. Fibroblasts cultured from skin biopsy from the patient metabolized radioactive pyruvate (final concentration 0.04–2 mmol/liter) to CO2at rates from 5 to 17% of that of fibroblasts from normal control subjects. Enzyme studies with fibroblast sonicates revealed a severe deficiency of the pyruvate dehydrogenase complex (about 8% of normal), and this error was localized to the first unit of the complex,i.e., the pyruvate dehydrogenase (about 4% of normal). Fibroblasts from both parents metabolized pyruvate to CO2at a slightly reduced rate, suggesting parental heterozygosity.SpeculationAn exact classification, which may have both prognostic and therapeutic implications, of patients suffering from the heterogenous group of diseases, congenital lactic acidosis, will be possible only when the various underlying defects have been demonstrated. Since we are probably dealing with errors localized close to the center of the energy metabolism, sophisticatedin vivoandin vitrostudies will be required to reach this goal. However, we expect each defect to give rise to secondary derangements in the patterns of organic acids and amino acids in serum and urine, which are more or less typical for each defect. Once these patterns are known, a precise biochemical diagnosis may be reached by comparatively simple examinations.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractA retrospective study aiming at detection of heterozygous carriers of blood adenosine deaminase (ADA) deficiency was carried out in nine families known to us because children had died of combined immunodeficiency (SCID). The trait was found in 3 of 9 parent couples, and in 14 other relatives. In two families one homozygous patient was identified. A total of 54 family members and 60 healthy control subjects were tested. Clinically, the patients were all characterized by marked lymphopenia, nearly normal immunoglobulin levels, and inability to produce antibodies. One homozygous patient recovered after transplantation of fetal liver and thymus and is immunologically normal 1.5 years afterwards.SpeculationA cause-effect relation between ADA deficiency and SCID is likely (8, 15, 30).In vitrothe accumulation of toxic metabolites as a consequence of the enzyme deficiency inhibits division and/or function of lymphoid cells.In vivo, the same mechanism might lead to SCID by impairing the lymphoid cells. In fact, clinical, immunologic and histologic findings are suggestive of a progressive destruction of lymphatic organs (14). Therefore, this particular kind of SCID is probably not caused by a primary defect of the lymphoid stem cell.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractInorganic lead, added to the diet of the suckling rat in high doses, produces an encephalopathy similar to that seen in the immature human. Pathologic changes of edema and hemorrhage are seen earliest and are most prominent in the cerebellum. In this study, we measured respiration in cerebral hemisphere and cerebellar mitochondria isolated from led-fed and age-matched normal rat pups. Lactating mothers were begun onad libitumfeedings containing 4% lead carbonate when their pups were 2 weeks old. Mitchondria were isolated by differential centrifugation. Oxygen consumption was measured polarographically. NAD-linked respiration was measured with oxidation of the substrate pair, glutamate and malate. Cytochrome oxidase (cytochromecoxidase, EC. 1.9.3.1) activity was measured in the presence of tetramethyl-p-phenylenediamine dihydrochloride (TMPD) and ascorbate. Within 2 days of starting lead feedings, rat pups showed a significant loss in body weight (P< 0.02) and, after 1 week, a significant loss in cerebral hemisphere wet weight (P< 0.01) compared with controls. Overt encephalopathy appeared in pups from two of nine litters receiving lead feedings for 1 week and in half of the litters after 2 weeks of feedings. None of the lead-fed mothers developed encephalopathic signs. With oxidation of the NAD-linked substrate pair, there was a progressive decrease, relative to controls, in ADP/O ratios in both cerebellar and cerebral mitochrondria from lead-fed animals. After 2 weeks these differences were significant in mitochondria from both regions (cerebellum, P<0.02; cerebrum, P<0.005). Respiratory control ratios were significantly lower in cerebellar mitochondria from lead-fed rats within 2 days of beginning feedings (P<0.02) and in mitochondria from both regions after 2 weeks of lead feedings (cerebellum, P<0.01; cerebrum, P<0.05). The decrease in control ratios in cerebellar mitochondria from animals receiving lead feedings for 1 week or less was due to a small decrease in state 3 respiration and a large, but inconsistent, increase in state 4 respiration. The decrease in control ratios in both cerebellar and cerebral hemisphere mitochondria after 2 weeks of lead feedings was due to a marked inhibition of state 3 respiration, relative to controls (cerebellum, P<0.01; cerebral hemisphere, P<0.05).In cerebellar mitochondria from lead-fed animals, cytochrome oxidase activity showed similar changes compared with controls: a highly significant (P < 0.001) increase within 2 days of beginning feedings and a significant (P < 0.01) decrease after 2 weeks of feedings.SpeculationThe effects of inorganic lead feedings were greater in mitochon- dria from cerebellum than from cerebral hemispheres. The changes in respiratory chain function, which appeared sooner after beginning lead feedings than any previously reported biochemical or morpho- logic effect on rat cerebellum, may constitute an early step in the pathogenesis of an encephalopathy which is predominant in this region of the suckling rat brain. In cerebellar mitochondria, inorganic lead may be acting as an uncoupling agent, such as dinitrophenol, affecting both NAD-linked respiration and cyto- chrome oxidase activity. The maturing brain may be most sensitive to the encephalopathic effects of lead at a critical period of rapid synthesis and increasing activity of respiratory enzymes. The greater effects on cerebellar mitochondria may be related to regional differences in mitochondria respiratory chain properties during this maturational period.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID

摘要:

ExtractTransformation and increased mitotic activity in donor lymphocytes exposed to specific antigens is considered by many to be a manifestation of cell-mediated immunity. In attempts to understand the apparent “sensitization” of individuals to respiratory syncytial virus (RSV) as a result of receiving inactivated RSV vaccine,in vitrolymphocyte transformation studies were carried out on infants who had received inactivated RSV vaccine and on infants who had received a similarly prepared inactivated African green monkey kidney (AGMK) cell-grown parainfluenza type 1 virus vaccine or a trivalent parainfluenza vaccine prepared in hen's eggs. Each group included some infants who had, and others who had not, undergone natural RSV infection under our observation before the lymphocyte studies.Lymphocytes were studied from 21 infants and young children who had received the inactivated RSV vaccine, 14 who received a similarly prepared inactivated parainfluenza 1 vaccine, and 5 who received a trivalent parainfluenza vaccine. Twelve of the RSV vaccinees and 14 of the parainfluenza vaccinees had been naturally infected with RSV as indicated by virus recovery and/or antibody rise between the time of vaccination and the lymphocyte studies. In comparing the arithmetic mean for RSV-specific transformation and mitotic activity there was a significant difference between RSV vaccinees and parainfluenza vaccinees whether one compared those who had undergone natural RSV infection or those who had not undergone natural infection. The difference between RSV vaccinees who had not undergone natural RSV infection and RSV-infected parainfluenza vaccinees also was significant. There was a greater level of transformation and mitotic activity in those who had experienced natural infection than those who had not among both RSV vaccinees and parainfluenza vaccinees, but these differences were not significant statistically.SpeculationWe take these findings to mean that natural RSV infection probably stimulates a systemic cell-mediated immunity response and that such a response is definitely induced after administration of killed RSV antigen. These findings are consistent with the hypothesis that cell-mediated sensitization may in some way contribute to the altered response to natural infection which occurred after use of inactivated RSV vaccine. Our findings do not support the hypothesis that systemic cell-mediated immunityper seis important in protecting against RSV infection. The findings also suggest the possibility that transplacentally conferred RSV lymphocyte sensitization might play a part in the pathogenesis of nonvaccine related RSV bronchiolitis which characteristically occurs during early infancy, frequently in the presence of measurable serum antibody.

ISSN:0031-3998    

出版商:OVID    

年代:1976

数据来源: OVID