摘要:

A 2.5-year-old Japanese girl who showed signs and symptoms compatible with classic Tay-Sachs disease and had altered β-hexosaminidase B and I1as well as completely deficient β-hexosaminidase A activity is reported herein.Heat treatment of the patient's serum and leukocyte samples showed the existence of 13.5–27.3% and 35.7% of the heat-labile component of β-hexosaminidase, respectively, such is usually considered to correspond to β-hexosaminidase A. The absence of β-hexosaminidase A activity was confirmed by DEAE-cellulose column chromatography and cellulose acetate paper electrophoresis. The patient's serum β-hexosaminidase also contained a significant amount of acid pH-labile components. The effects of buffer concentrations on the activities of total and heat-labile components of the serum β-hexosaminidase of the patient differed from those of the control subjects.Heat treatment of the each component of serum β-hexosaminidase which had been separated by DEAE-cellulose column chromatography showed that β-hexosaminidase B and I1in the serum from this patient were heat labile as compared with those from the control subjects, and the other component I2was less heat labile at 50° for 3 h.There were no differences in the km values of β-hexosaminidase B, I1, and I2for the synthetic substrate 4-methylumbeIli-feryl N-acetyl-β-D-glucosaminide before and after heat treatment at 50° for 3 h among the reported patient, another patient with classic Tay-Sachs disease, and a normal infant.SpeculationIn prenatal diagnosis of such patients as reported herein, it will be necessary to confirm the absence of β-hexosaminidase A in amniotic fluid and/or amniotic fluid cells by methods other than the heat-inactivation method, e.g., electrophoresis or ion-exchange column chromatography.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

The economy of Cl-, K+, and Mg++, extracellular volume (ECV) and plasma volume, and the role of hyperreninemia and hyperaldosteronism were explored in 22 patients with congenital chloride diarrhea. Stool volume was in significant correlation with its Cl-, Na+and K+content, the correlation being significantly better with Cl-content than with the Na+content. Low fecal Cl-concentrations were seen in chronic hypochloremic contraction, but acute episodes did not cause reduction of fecal Cl-concentration from the basal level of 140–150 mmol/liter. The adequate condition (defined as normal serum electrolyte concentrations and blood pH, and presence of Cl-in urine) was associated with high total exchangeable Cl-and ECV. This excess Cl-and ECV roughly equalled the high daily fecal amount of Cl-and volume. Reduced ECV was accompanied by high renin activities and hyperaldosteronism, but in the adequate condition these were normal. Hyperaldosteronism caused a decrease in urinary Na+-K+ratio and, after the age of 2–6 months, in the fecal Na+-K+ratio. Total exchangeable K+was normal in the adequate condition. No Mg++depletion was present, although the patients lack Mg++substitution. The adequate condition could be maintained with an oral supplement of NaCl, KCl and water.SpeculationHyperreninemia, hyperaldosteronism, and hypokalemic alkalosis in congenital chloride diarrhea (CCD) are secondary to hypochloremic ECV contraction and can be completely corrected with adequate substitution. Mg++depletion does not play a part in CCD. The intestinal response to hyperaldosteronism appears later in the intestine than in the kidney in the newborn CCD patient and presumably also in the normal newborn.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

The 24-hr urinary excretions of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured in seven males with untreated congenital adrenal hyperplasia. The patients aged 1–10 years had urinary FSH concentrations of 4.1–6.7 IU/day (normal = less than 2.5 IU/day). Elevated levels of 13.6 IU/day were found in the 81-year-old patient. During suppressive steroid therapy, the FSH excretion fell to the normal range in the one so studied; therapy was reduced in two patients and their FSH excretion rose by 20–30% in a 4-month period. The FSH production rate was 41.5 and 40.2 IU/day in the 1-and 6-year-old patients before therapy (these levels being at the upper limit of the normal range for adults). After 2.5 years of the FSH production rate in one of them fell to 10.3 IU/day.The excretion of LH was elevated for age and was 5.9 and 11.8 IU/day in the 1− and 6-year-old untreated patients (normal therapy, range = less than 3 IU/day). After suppressive therapy for 2.5 years, the LH excretion in the 1-year old fell only to 4.7 IU/day. In two patients, therapy was reduced for 4 months and the LH excretion actually fell from 5.1 to 2.9 and 10.0 to 7.4 IU/day. Similarly, the 81-year-old untreated adult male showed an LH excretion of 16.4 IU/day, which is lower than the normal adult range of 22.3–45.1 IU/day. The LH production rates in the 1− and 6-year-old patients before therapy were 166 and 141 IU/day, respectively both being lower than the range of 247.7–464.5 IU/day found in normal adult males.SpeculationThe increased FSH production and excretion could be due to hypothalamic-pituitary stimulation by increased production of androgens or their precursors or from increased estrogens from the adrenal glands, or even to abnormal metabolites such as 17-hydroxy progesterone.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Insulin infused into a sheep fetus over a 3-hr period at the rate of ∼0.24 U-kg-1-h-1increased fetal glucose uptake (utilization) from 4.4 ± 0.7 mg. min-1. kg-1to 6.9 ± 0.9 mg.min-1kg-1as compared to a noninsulin control period. Insulin administration did not alter fetal oxygen consumption (8.6 ± 0.7 ml.min-1.kg-1vs. 7.7 ± 0.7 ml.min-1kg-1), umbilical blood flow (220 ± 1 ml.min-1kg-1vs. 209 ± 16 ml.min-1.kg-1), or the placental clearances of antipyrine (114 ± 7 ml.min-1. kg-1vs. 109 ± 8ml.min-1.kg-1) and urea (24.5 ± 2.2 ml.min-1.kg-1vs. 25.0 ± 2.1 ml.min-1.kg-1). Fetal plasma glucose concentration fell significantly (0.22 ± 0.01 mg.ml-1to 0.16 ± 0.01 mg.ml-1) during insulin infusion. The insulin effect on fetal glucose uptake occurred over a range of maternal glucose concentrations (0.32 → 0.78 mg.ml-1), which were not altered by the infusion of insulin in the fetal compartment.Insulin has a specific effect on increasing fetal glucose uptake and utilization.SpeculationThe effect of insulin on increasing transplacental fetal glucose uptake is consistent with a growth-promoting role for insulin in the fetus. This action of insulin might be due to a direct effect of insulin on the mechanisms of placental glucose transport, to an alteration of placental glucose catabolism, or simply to the effect of insulin on the transplacental gradient of glucose.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

It has been suggested previously that delayed closure of the ductus arteriosus in premature infants is related to an ineffective constriction in response to an increase in arterial PO2. The contractile effects of increased PO2and excess K+were studied in rings of ductus arteriosus from early (70 ± 4 days, n> = 9) and late (137 ± 3 days, n> = 11) gestation fetal lambs. Studies were performed in a laboratory using overhead fluorescent lighting or in a dark, enclosed box. Room light relaxed the oxygen-induced contraction in immature vessels but had no significant effect on the K+-induced contraction. Room light did not alter either the oxygen or K+-induced contractile responses in mature vessels. When comparing oxygen induced contractions in room light in immature vessels (0.27 ± 0.13 g, n> =9) vs. mature vessels (0.82 ± 0.06 g, n> = 11) there appeared to be an increased response to oxygen with advancing gestational age. However, when the oxygen-induced responses of immature (0.59 ± 0.15 g, n> = 9) and mature (0.82 ± 0.06 g, n> = 11) vessels were performed in an environment excluding room light, no significant gestational difference was observed. The role of oxygen in delayed closure of the ductus arteriosus of premature infants will need further evaluation.SpeculationThe difference in sensitivity to photorelaxation between rings of ductus arteriosus from immature and mature lambs may be associated with biochemical differences in vessels between early and late gestation.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

The uptake and metabolism of [3H]leucine, [U-14C]glucose, and [3H]palmitate were studied in rabbits aged −3, 1, 7, 28, and 90 days up to 1–1.5 years. Although lung composition did not change markedly, there were great differences in lung metabolism between the perinatal period (late fetal and newborn) and later stages of development.Leucine incorporation into lung protein was highest (3.1–3.4 nmol/mg protein/hr) in late fetal and newborn rabbits and decreased rapidly thereafter. Palmitic acid incorporation decreased during the first week after birth from 150 nmol/100 mg/hr to 85 nmol/100 nig/hr at 7 days of age; it increased thereafter to 170 nmol/100 mg/hr at 4 weeks of age and remained at that level throughout the entire period studied. Glucose uptake and lactate production were higher in fetal lungs than in all other age groups. Lipid biosynthesis from glucose was 2–4 times higher in fetal lungs than at all other ages; furthermore, more than 60% of glucose carbon atoms channeled into lipid was incorporated into fatty acids, whereas at all other ages glucose was chiefly a precursor of lipid glycerol.SpeculationOur data suggest that late fetal lung has a high metabolic activity that corresponds to the high synthetic demands of a rapidly growing and differentiating organ. Our study shows a higher glucose uptake in fetal and newborn lung than at later ages. Of special significance is the finding that lipid and, especially, fatty acid synthesis from glucose, is highest in the fetal lung. Since glucose is incorporated chiefly into phospholipids, the 7–8 times higher incorporation of glucose carbons into phospholipid fatty acid could have special significance for surfactant biosynthesis.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Because very little is known regarding the control of enzyme secretion in developing parotid glands, the effects of various secretagogues on cyclic AMP levels and amylase release were studied in rats at various times after birth. In parotid fragments or slices incubated with isoproterenol or epinephrine (40 μM) in vitro, neither cyclic AMP elevation nor amylase release was achieved at 8 days postnatally. In in vivo studies, secretion of amylase at this age was also refractory to stimulation with these hormones or carbamylcholine. In animals older than 15 days, highly significant rise in cyclic AMP content occurred 5 min after exposure of the glands to the catecholamines in vitro, and the magnitude of this elevation was incremental with age. Thus, in 15-day-old animals adrenergic stimulation produced a 2-fold rise in cyclic AMP levels (from 9.3 ± 1.0 pmol/mg protein to 20.9 ± 4.7, mean ± SE); at 25 days the increase was 7–8 times the basal value (from 2.7 ± 0.3 to 21.3 ± 3.9); and at 8 weeks the rise was 8-fold with epinephrine (from 3.2 ± 0.3 to 24.4 ± 7.5) and 12-fold after isoproterenol (from 3.2 ± 0.3 to 39.2 ± 9.2). At these ages, adrenergic stimulation led to a 2− to 3-fold increase in amylase secretion compared to unstimulated control levels. When isoproterenol (16 μg/g body weight) was injected intraperitoneally in intact animals 15 days of age or older cyclic AMP levels 5 min later were increased 2–3 times in 15− and 25-day-old animals (from 13.9 ± 4.4 to 49.3 ± 3.9 and 31.3 ± 4.0, respectively) and >100-fold in mature animals (1211 ± 437). Greater than 40% of the stored amylase was released from the glands in 30 min, a quantity comparable to that found in vitro. The data demonstrate that the responsiveness of the parotid gland to catecholamines is age dependent, and that development of secretory function precedes full morphologic and biochemical development.SpeculationThe identification of a stage in exocrine development when the immature parotid glands are refractory to secretory stimuli represents an important model for the study of stimulus-secretion coupling. The acquisition of mature secretory function may depend upon the relationship between the number of cell surface hormone receptors and acinar maturation.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

The effect of cortisol, niethylprednisolone, and ACTH on (Na+-K+)-ATPase activity in developing cerebral cortex has been measured. Stimulation of (Na+-K+)-ATPase by these agents has been found in whole brain homogenates of kittens as early as age 8 days, and in whole homogenates and light microsomal fractions of young rats at 14 and 28 days. (Na+-K+)-ATPase activity in animals treated with corticosteroids or ACTH for 4 days was found to be 15–30% higher than activity in littermate controls. Brain potassium concentration was increased in 14-day-old rats treated with methylprednisolone.SpeculationCorticosteroid hormones and ACTH are effective in the treatment of seizures in infancy, especially in patients with infantile spasms and hypsarrhythmia. Stimulation of (Na+-K+)-ATPase activity by these hormones provides a plausible mechanism for the anticonvulsant effect.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

A ciliostatic factor has been isolated from cystic fibrosis (CF) saliva by dialyzing it from purified α-amylase prepared by a glycogen-complex method. This method of isolating the CF factor is an improvement over the previously employed heparin procedure. The activity of the isolated factor is proportional with concentration using the oyster gill ciliostatic assay and in its inhibition of mammalian glycogen debranching enzyme. The ciliostatic action of the factor can be reversed by heparin under certain conditions. The type of inhibition of the debranching enzyme by the isolated CF factor indicates that its chemical structure is similar to that observed with hydroxyalkylamines and polyamine metabolites. Physical properties of the isolated factor indicate that it is of low molecular weight and is labile as a function of pH and temperature. At neutral pH the conditions under which it is maintained have a direct effect on the length of time that it is stable.SpeculationThese studies indicate how the stability of the ciliostatic CF factor isolated from saliva is related to the physical conditions to which it is exposed. This information should be of value in evaluating its activity as well as in investigations into its chemical nature.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID

摘要:

Neonatal rats (4–7 days old) and adult rats (approximately 80 days old) were continuously exposed to either 96–98% oxygen or air. Examination of the lungs of neonatal rats, who survived 5 days of oxygen exposure with no evidence of respiratory distress, showed significant increases in the pulmonary superoxide dismutase (SOD) activity (peak value: 144% of air-exposed controls), glutathione peroxidase (GP) activity (126%), glutathione reductase (GR) activity (122%), reduced glutathione (GSH) level (176%), and glucose-6-phosphate dehydrogenase activity (151%). Adult rats, most of whom succumbed within 3 days of oxygen exposure, did not show any significant increase in the activities of pulmonary SOD, GP, GR, and the level of GSH as compared to the air-exposed adult animals. Glucose-6-phosphate dehydrogenase was significantly elevated in the 72-hr oxygen-exposed adult rats. It. is concluded that increases in the lung complement of SOD, GR, GP, and GSH in the neonatal rat during oxygen challenge may provide the mechanism(s) for their increased tolerance to hyperoxia-induced lung injury as compared to the adults.SpeculationFurther knowledge about the role of the antioxidant defense mechanism(s) of the neonatal lung may have important implications in the pursuit of the etiology of neonatal respiratory disease and in the identification of agent(s) that may minimize pulmonary toxicity associated with oxygen therapy.

ISSN:0031-3998    

出版商:OVID    

年代:1978

数据来源: OVID