摘要:

ExtractSerum concentrations of hemopexin, transferrin, and albumin were measured for 12 fetuses between 14 and 36 weeks of gestational age. Hemopexin levels ranged from 7 to 64 μg/ml, transferrin levels ranged from 280 to 928 μg/ml, and albumin levels ranged from 13 to 59 mg/ml. In general, the serum concentrations of these three proteins increased with advancing gestation.Placenta, thymus, and colon did not incorporate14C-labeled amino acids into hemopexin, transferrin, or albumin. By contrast, radioimmune precipitates for five culture supernatants of liver indicated significant synthesis of albumin and hemopexin. [14C]Albumin accounted for 22–73% and [14C]hemopexin 1.1–4.2% of the total14C-labeled proteins. In each instance, the [14C]transferrin was below 1% of the total 14 C-labeled proteins.SpeculationThese data show considerable synthesis of albumin and hemopexin, but not transferrin, by the liver during fetal life. That hemopexin levels are lower in fetal than adult sera may reflect an increased requirement for heme disposal. Possibly, the increased turnover of hemopexin is related to the shortened lifespan of fetal in comparison with adult erythrocytes.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractOur studies of a mentally retarded male with extremely elevated levels of α-aminoadipic acid and α-ketoadipic acid in his urine have led to the description of a new metabolic defect, α-ketoadipic aciduria. Analysis of the urine and serum from the patient's family revealed that the patient (KW) had a mentally and physically normal sister (CW) with the same metabolites elevated, but the rest of the family appeared normal.SpeculationThe presence of elevated levels of α-ketoadipate in the urine of the reported sibs suggests a reduced level of α-ketoadipic acid dehydrogenase. This enzyme has not been purified in humans, but is considered to be α-ketoglutaric acid dehydrogenase in several nonhuman animals. We are presenting evidence that would suggest that in humans these may be separate enzymes, or that more than one form of the α-ketoglutaric acid dehydrogenase exists.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractTime-corrected measurements of transplacental and transamniotic potentials were made in the fetal rat on the 20th day of gestation. These averaged 14.3 mV and 18.4 mV, respectively. The measured maternal potassium concentration in plasma of 4.8 mEq/liter and these potential measurements were used in the Nernst equation to predict the fetal concentrations in plasma. The concentration in amniotic fluid was predicted, using the potentials and either the fetal or maternal plasma concentration. The predicted concentrations in fetal plasma and amniotic fluid were 2.8 and 2.5 mEq/liter, respectively. The sampling time-corrected potassium concentration in fetal plasma was 2.9 mEq/liter and the mean in amniotic fluid was 4.6 mEq/liter. The observed concentration in amniotic fluid is significantly higher than the predicted level.SpeculationPotassium is passively distributed between maternal and fetal plasma according to electrochemical gradients. By contrast, there is active transfer of this ion into the amniotic fluid, probably from the fetal plasma across the kidney.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractAH enzymes of the urea cycle are demonstrable in circulating leukocytes. They show the same relative activities as those in liver except for argininosuccinate synthetase + lyase (combined) which seems to be disproportionately active.To see whether leukocytes reflect liver activity, blood from patients with three hepatic urea cycle disorders was tested. In each case, the leukocytes showed the same enzyme deficiency as was apparent from a liver biopsy (Table 4). Leukocyte assays appear to be reliable indicators of the enzyme lesions in inherited urea cycle enzyme defects and therefore may obviate the need for liver biopsy.SpeculationBy using radioactive substrates to improve sensitivity it should be possible to reduce the blood sample size required (from 30 ml for the less active enzymes) to amounts suitable for use in neonates. Heterozygote detection in relatives of affected patients may also be feasible.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractHormonal balance was studied in eight insulin-treated diabetic children who had excessive glycosuria. Glucose, growth hormone, and cortisol in plasma were determined every 0.5 hr for 48 hr. Total catecholamines and glucose were measured and tests for ketones done in 2-hourly collections of urine.Intermittent hypoglycemia as low as 20 mg/100 ml and swings of the blood sugar curve by 200–300 mg/100 ml within 2–4 hr were documented in most patients.Peaks of growth hormone concentration in plasma (8–78 ng/ml) followed almost every sharp fall in blood glucose; these peaks were usually followed by abrupt rises of glucose and prolonged hyperglycemia.Cortisol concentration was usually within the high normal range; there was no consistent relationship to the concentration of glucose.Urinary excretion of catecholamines in most patients was between 1 and 6 μg/hr; three patients excreted up to 8–23 μg/hr during short periods and up to 190 μg in 24 hr. The causes for the high excretion of catecholamines are unknown and may not have included hypoglycemia.SpeculationExcessive production of growth hormone and possibly other hormonal antagonists of insulin may be provoked by hypoglycemia and other physiologic stresses in diabetic children. The resulting hyperglycemia may prompt the administration of increasing doses of insulin which, in turn, contribute to a vicious cycle of hypoglycemia alternating with hyperglycemia.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractWe have studied a 9-year-old boy with agammaglobulinemia treated for the past 6 years with exogenous γ-globulin who was noted to have an immunoglobulin (Ig) M level of 35 mg/100 ml and circulating B cells as determined by immunofluorescence. Of the circulating lymphocytes, 41% had α-immunoglobulin heavy chains, 3% γ chains, and 3% μ chains. Synthesis of γ heavy chain classes showing wide heterogeneity and α and μ chains of restricted mobility was demonstrated by radioimmunoelectrophoresis. Because of the patient's poor clinical response to exogenous γ-globulin administration and the paradoxic presence of circulating B cells, with the capacity to synthesize immunoglobulinsin vitro, we elected to begin a course of therapy with transfer factor. After the initial four doses of transfer factor (2 × 108lymphocytes/dose) his serum IgG rose from 50 to 130 mg/100 ml, the same level which he had previously attained during continuous exogenous γ-globulin therapy. His serum IgG has remained at this level for the past 12 months with trimonthly booster doses of transfer factor. The patient has not required any additional γ-globulin therapy and he has remained clinically asymptomatic.SpeculationOur studies in a patient with agammaglobulinemia have shown that transfer factor therapy may affect immunoglobulin synthesis. The concurrent discontinuation of exogenous γ-globulin administration makes it difficult to attribute the changes to only one or another aspect of therapy. We await further reports of the effects of transfer factor in the therapy of patients with B cell disorders.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractIncreased pulmonary blood flow was produced in 1-month-old piglets by means of left pneumonectomy, arteriovenous fistulas in the neck, and a combination of both. Physiologic and histologic studies of the pulmonary vascular bed were done 1–9 months after operation.A progressive, moderate increase in pulmonary artery (PA) pressure was observed, especially between 1 and 6 months after surgery. This was flow related, i.e., the group with the highest flow (pneumonectomy plus fistula) was found to have the most prominent increase in pressure. Mean PA pressure at 6 months was 28.7 ± 0.07 mm Hg in this group, vs 24.4 ± 0.48 mm Hg in the group with pneumonectomy alone and 17.2 ± 0.48 mm Hg in controls (P< 0.01). The pressure response to hypoxia in pigs with high pulmonary blood flow was not different from that found in control animals.Histologic studies revealed that small arteries and arterioles of pigs with high pulmonary blood flow had a decreased relative wall thickness because of dilation up to 6 months follow-up. This was flow related, the group with the highest flow having the lowest wall thickness to vessel diameter ratio; relative wall thickness (in percentage of the vessel diameter) at 6 months was 6.1 ± 0.44% in pigs with pneumonectomy plus fistula, vs 9.6 ± 0.40% in the group with pneumonectomy alone and 11.2 ± 0.61% in controls (P< 0.01). In the group with the highest flow, thick walled arterioles appeared at 9 months follow-up, scattered among dilated ones; mean medial wall thickness in these animals increased significantly between 6 and 9 months after operation, ranging from 6.1 ± 0.44% to 11.3 ± 0.73% (P< 0.01).In five animals with high flow, the right PA (main branch) showed patchy intimal thickening, small cystic spaces filled with mucopolysaccharides in the media, and muscular hypertrophy.SpeculationSome changes usually seen in pulmonary hypertension were produced in this model by high pulmonary blood flow in the presence of only mild to moderate elevation of PA pressure. The dilation observed in the pulmonary arteries and arterioles may have been a pathogenetic factor; indeed, it is likely that wall tension rather than intravascular pressure induces vascular changes; wall tension (according to Laplace's law) depends on vessel diameter as well as intravascular pressure. Therefore, in a dilated vascular bed, wall tension will increase considerably with only moderate increase in PA pressure, inducing changes usually seen with more severe degrees of pulmonary hypertension.

ISSN:0031-3998    

出版商:OVID    

年代:1975

数据来源: OVID

摘要:

ExtractThe specific activity of argininosuccinate synthetase (micromoles of14CO2per milligram of protein per hour) was 0.00104 and 0.00087 in fibroblasts derived from two patients with citrullinemia, and was undetectable in both fibroblasts and cultured lymphocytes from a third patient. In five obligate heterozygotes the specific activity in fibroblasts was 0.012 0.029 and in nine control subjects was 0.058 ± 0.014 (0.030–0.076). In both control and patient cells, the maximum activity was obtained at pH 8.5 and there was no inhibition of normal argininosuccinate synthetase by any of the mutant cells.Kinetic studies were consistent with decreased binding of citrulline and/or aspartate in fibroblasts from all three patients. The Kmfor citrulline was 4.2 × 10−3and >2.0 × 10−2M for the enzyme from patients 1 and 2, respectively (normal 1.1 × 10−4M). Corresponding Km values for aspartate were 1.8 × 10−2and >6.5 × 10−3M, respectively (normal 3.4 × 10−5M). Hill constants derived from the citrulline substrate curves from patients 1 and 2 were 1.01 and 1.50 (normal 0.91). Corresponding constants obtained from aspartate binding curves were 1.06 and 1.35, respectively (normal 0.97).The activity of homoargininosuccinate synthetase was undetectable in fibroblasts from all three patients and a control subject.SpeculationHeterogeneity of the primary enzyme defect will become a frequent observation in many inborn errors of metabolism. In disorders of the urea cycle, alternative and as yet unknown pathways of urea formation may be discovered.

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