摘要:

Prothrombin of newborns was investigated by means of the quantitative immunoelectrophoresis and the two-dimensional immunoelectrophoresis. The plasma of 10 of 24 healthy term newborns and of 5 preterm infants taken immediately after birth showed one prothrombin precipitate in the α-2-β-globulin position when a buffer containing 25 mM calcium lactate was used. No differences in the mobility and form of the precipitate could be observed as compared to healthy adults. The plasma of the other 14 term newborns and one small-for-date infant showed two precipitates, one in the α-2-β-globulin position and a second in the α-1-globulin position. Twenty-four hr after the injection of vitamin K, the precipitate in α-1-globulin position was no longer evident. When a buffer without calcium was used in the two-dimensional immunoelectrophoresis, only one precipitate in the α-1-globulin position was found in all newborns. In the quantitative immunologic determination, the prothrombin was found to be decreased as compared to that of adults. The quantitative immunologic determination and the activity assay gave equal results in those infants who had only one precipitate in the two dimensional immunoelectrophoresis. In those newborns, who had two precipitates, the quantitative immunologic determination gave higher results than the measurement of the activity assay.From this study, no evidence of differences between the prothrombin of newborns and that of adults could be derived. Vitamin K deficiency, as judged from the appearance of a second peak in α-1-globulin position in the two dimensional immunoelectrophoresis was a frequent finding in term newborns, even on the 1st day of life.SpeculationVitamin K deficiency is not only an acquired disease in newborns due to an inadequate intake of vitamin K with certain formulas during the 1st days of life, but is also a disease that may exist in term newborns, after a normal pregnancy, before feeding. The significance of an efficient diet of the mother or of vitamin K supplementation to the mother remains to be elucidated.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Chondro-osseous tissue from four patients with the Kniest dysplasia was studied histochemically using a new plastic embding technique. Extensive vacuolar changes were observed p-1 throughout the endochondral growth plate and adjacent resting cartilage. These changes occurred within the cartilage matrix and also in the lacunae of degenerating chrondrocytes. The septa of the lesions contained chondroitin sulfate, but little keratan sulfate or collagen. Resting cartilage not adjacent to the growth plate stained irregularly and showed few of the vacuolar lesions, and chondrocytes were enlarged and contained cytoplasic inclusions, but no vacuolar material. Thus, there appears to be a sequence of events initiated by cellular accumulation of a substance and progressing to cellular and matrix degeneration.SpeculationThe findings suggest that there may be a defect in the synthesis, structure, or secretion of a major cartilage matrix component (e.g, proteoglycan, collagen) which leads to its accumulation in the chondrocyte rough endoplasmic reticulum. Both cellular and matrix degeneration subsequently occur either due to a toxic effect of this material or to the absence of the normal molecule.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The present series of experiments was designed to determine whether the piglet has mature cardiorespiratory responses to the administration of phenyl diguanie (PDG) similar to those reported in adult mammals. A total of 26 acutely instrumented piglets aged 2–23 days were lightly anesthetized with sodium pentobarbital. After control conditions were established, PDG was injected into the right atrium. Each animal was its own control for determination of presence and magnitude of aortic pressure, heart rate, respiratory rate and volume, and blood flow responses to test doses of PDG. A fall in blood pressure was observed in all animals within 2–4 sec after right atrial injection of PDG. Bradycardia occurred and a transient cardiac arrhythmia, consisting of 2nd and 3rd degree heart block, was observed in most animals; the latter has not been previously reported. Apnea followed by rapid shallow breathing was observed in most animals. This respiratory effect was more pronounced in the younger animals. After atropine, PDG elicited a monophasic rise in aortic pressure; the cardiac rhythm and rate changes were abolished. However, the apneic response was retained. Subsequent bilateral vagotomy abolished the hypotensive effect on PDG. Such results suggest the possibility that the piglet's cardiorespiratory response to the administration of PDG may be evoked by stimulation of type J pulmonary receptors. These have been postulated to be responsible for the triad of responses of hypotension, bradycardia, and apnea seen in other species after PDG administration.SpeculationAt present, there is no explanation for the apnea and bradycardia observed in premature infants with Respiratory Distress Syndrome and/or a large patent ductus arteriosus. Mild interstitial pulmonary edema has been postulated to be the physiologic stimulus for the type J (juxtacapuiary) pulmonary receptor. The authors speculate that the piglet's response to PDG which includes apnea, hypotension, and bradycardia may be mediated by artificial stimulation of the J receptor. It is possible that in the human neonate, an immaturely controlled or an inappropriately strong response to the pathophysiologic stimulation of pulmonary edema may be a mechanism for the clinical symptoms of apnea and bradycardia in the small neonate.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Initially, it was observed that whereas the propionyl CoA carboxylase (PCC) activity in peripheral blood leukocytes of a 13-month-old girl with isolated PCC deficiency who had been given biotin supplements (4.5 mg/day) for 6 months was only 3% of control, her βMCC activity was greatly elevated at 20 times control activity. After biotin supplements were discontinued, βMCC activity in leukocyte extracts declined over 3 wk to values just above the normal range with no associated change in PCC activity; readministration of biotin caused her βMCC activity to rise in 3 days to the initial elevated values. These results prompted measurement of PCC and βMCC activities in leukocyte extracts of three normal adults given 20 mg biotin orally per day. Their PCC and βMCC activities increased 2− to 3-fold and 4− to 9-fold, respectively, within 7–10 days. After biotin was discontinued, both enzyme activities returned to normal in 4–5 wk. The effect of high concentrations of biotin and βMCC activities was also investigated in cultured fibroblasts from three control subjects. PCC activity increased only 11% in normal fibroblasts grown in medium containing fetal bovine serum and high concentrations of biotin (900 μg/ml). However, PCC and βMCC activities were increased 70–75% and 120–140%, respectively, when confluent normal fibroblasts were incubated in medium containing 10% human serum and 0.1–1.0 μg/ml biotin. This stimulation was independent of the fibroblast growth cycle. Furthermore, cycloheximide failed to inhibit the increase in PCC activity caused by biotin, suggesting that the enhanced activity in fibroblasts was not due tode novocarboxylase synthesis. These studies demonstrate that high concentrations of biotin can stimulate biotin-dependent carboxylases in human tissues, possibly by converting apocarboxylase to holocar-boxylase or by activating preexisting inactive holocarboxylase.SpeculationThe stimulation of human propionyl CoA and β-methylcrotonyl CoA carboxylase activities in peripheral blood leukocytesin vivoand in cultured skin fibroblasts by high concentrations of biotin represents a promising model for investigating the cellular metabolism of biotin in man.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The distribution of64Cu is reported in whole blood, plasma fractions, urine, and stool in an adult volunteer and two patients with Menkes' kinky hair disease (trichopoliodystrophy) after in-tragastric and iv administration. In the adult, after oral circulating64Cu, showed an initial peak at 40–60 min which was 4% of the total dose (or 5% of the amount calculated to be absorbed), a small secondary peak at 3.5% by 4 hr, then a gradual rise to 32 hr. Approximately 55% of the whole blood radioactivity was in the plasma from 8–48 hr. In the two patients, after ingestion or injection, there was no early blood peak and about 10% of both the absorbed or injected copper persisted in the circulation from the 4th hr to beyond 24 hr in a pattern similar to that in the adult, but less than 40% of the 6464Cu, was in the plasma fraction after 4 hr. In all subjects, the albumin/globulin ratio of radioactivity fell progressively, suggesting prompt ceruloplasmin synthesis by the liver. No radioactivity was detected in cerebrospinal fluid 10 hr after64Cu, injection in patient 2. Urinary excretion of64Cu, in the adult appeared to be linear after 6 hr (approximately 0.08% of the total dose per 24 hr). In patient 1, it was half as great (0.04%/24 hr), but if calculated on the assumption that only 6% of ingested copper was absorbed in patient 1, his urinary excretion rate, 0.67%/24 hr would be eight times that of the control, strongly suggestive of renal inability to conserve copper. In the adult, stool radioactivity totaled 24% of the ingested dose by 48 hr. In patient 1, stool radioactivity was already 94% by 48 hr and in patient 2, after iv64Cu, stool radioactivity was only 2.8% by 96 hr. This low stool radioactivity after injected copper indicated minimal biliary loss of radiocopper, and ruled out a rapid enterohepatic recycling of copper in this disease. Because 94% of a physiologic dose of64Cu, was in the 48-hr stool in patient 1,SpeculationThe data are interpreted as confirming that there is a mucosl block to copper absorption in Menkes' disease, but that this block is incomplete. Despite depleted circulating copper, erythrocyte uptake appeared normal or high in these patients, and hepatic incorporation into ceruloplasmin seemed to be unimpaired. There may be renal transport abnormalities in Menkes' disease as well, because of the unexpectedly high urinary64Cu, excretion in the presence of hypocupremia. Perhaps an abnormality of blood-brain copper distribution is responsible for the severe neurologic features of this disease.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Immature and mature rabbit neonates were observed for production of intrapulmonary foam during the first 5–10 min of extrauterine life. Viability at birth of littermates was determined. In addition, lungs from neonates that had breathed 3–5 min after birth and from fetuses that had not breathed were studied during manual inflation to maximal volume and deflation to zero trans-pulmonary pressure (minimal volume). Lung wet/dry weights and amniotic fluid lecithin-to-sphingomyelin ratios were determined. Compared with mature subjects, body weights and lecithin-to-sphingomyelin ratios were significantly lower in the immature group, and total water content was significantly higher. No immature neonate lived to 3 hr, whereas all mature neonates were robust, active, and normal. Both spontaneous breathing up to 10 min and manual inflation-deflation were associated with intrapulmonary foam in each mature lung, but with little or no foam in immature lungs. The following were characteristic of immature lungs: 1) Airways and terminal lung units (TLU) were generally liquid-filled at zero transpulmonary pressure. 2) When lungs were inflated to maximal volume, all TLU appeared aerated. 3) However, during deflation liquid refilled most TLU and airways and >95% of the air previously introduced was returned to the syringe. 4) Air trapped in TLU at end deflation was not due to airway collapse, but to relatively early refilling of more proximal adjacent airways which thereby prevented air from leaving more peripheral TLU. Similar studies of mature lungs confirmed our previous report (Pediatr. Res.,I2: 1070 (1978)) that intrapulmonary foam is produced at the onset of breathing at birth and, also, during initial manual inflations of the liquid-filled fetal lung. Thus, the striking difference between the mature and immature lungs is the inability of the latter to produce foam. This is related to immaturity of the surfactant system, inability to establish residual volume at the onset of breathing, and retention of liquid in potential air spaces.SpeculationImmaturity of the surfactant system inhibits the production of intrapulmonary foam at the onset of air-breathing at birth. This deficiency, which is characteristic of immature lungs, retards residual volume formation and fetal pulmonary fluid absorption. Therefore, pulmonary blood flow, gas exchange, and alveolar lining formation are compromised.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

In an attempt to determine the effect of a toxic insult occurringin uteroon the developing liver, fetal amniotic cavities of timed-pregnant (16-day) Sprague-Dawley rats were injected with varying concentrations of E.coliendotoxin. Controls were sham-operated or saline-injected fetal rats. Five days after injection, the pregnant animals were killed;14C-Ieucine was injected subcutaneously into the newborns, and their livers were removed, prepared for histo-logic examination and for analysis of radiolabeled protein incorporation. A significant increase in the number of hepatic giant cells (giant cells/mm2) was noted in fetal rats injected with endotoxin compared to the controls (P < 0.01). In addition, the incorporation of14C-leucine into total liver protein and immuno-precipitable albumin of endotoxin-injected fetuses was significantly lower than that of control animals (P < 0.01 and P < 0.02, respectively). In contrast,14C-leucine incorporation into immuno-precipitable α-fetoprotein was significantly greater in endotoxin-injected fetuses than in controls (P < 0.02). Also, serum α-fetoprotein levels were significantly (P < 0.01) higher in the endotoxin-injected fetuses.These data suggest that intrauterine insult with endotoxin during late fetal development results in hepatotoxicity manifested as giant cell induction and disrupted protein metabolism. The changes (hepatic giant cell response and elevated serum levels of α-fetoprotein) in rat liver parallel those reported in human newborns with neonatal hepatitis syndrome. Therefore, it may be suggested that the endotoxin-injected fetal rat may represent an appropriate animal model for the study of the pathogenesis of neonatal hepatitis in man.SpeculationThe development of an animal model for neonatal hepatitis syndrome may ultimately provide the basis for a better understanding of the pathogenetic mechanisms responsible for both morphologic and biochemical abnormalities noted in this spectrum of hepatobiliary diseases. Of particular importance is the more precise characterization of the hepatic giant cell frequently demonstrated in neonatal hepatitis. This cell type could contribute to the pathogenesis of hepatitis by releasing secretions that help to regulate changes in the hepatic cellular environment such as proteolysis, inflammatory cell infiltration, or disruption of the biliary tract epithelial surface, and thereby, contribute to the various manifestations of disease. Furthermore, there could be modification of these tissue reactions by coexisting genetic factors such as renewed synthesis of fetoprotein after reversion of fetal hepatocytes to an earlier stage of development. The synthesis and release of this developmental protein may also be of importance in immunoregulation during intrauterine existence.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

A 1-yr-old male domestic shorthair cat was referred to the University of Pennsylvania Veterinary Hospital with a history of progressive lameness. The cat had a short, broad face, frontal bossing, a depressed nasal bridge, small ears, bilateral corneal clouding, and thickened skin over the dorsal aspect of his neck. Radiographically, the cervical vertebrae were wide, assymetrical, and appeared nearly fused; there was bilateral coxofemoral sub-luxation and pectus excavatum. Electrophoresis of glycosamino-glycans (GAG) from the urine revealed an excess of both dermatan sulfate and heparan sulfate. The incorporation of35SO4into the GAG of fibroblasts revealed an exaggerated accumulation of [35S] -glycosaminoglycans. By light microscopy, neurons swollen with vacuolated cytoplasm were observed. By electron microscopy, the spinal cord neurons contained membrane-bound “zebra bodies”. Membrane-bound inclusions containing granular material or an occasional myelin-like figure were present in hepatocytes. The activities of seven lysosomal hydrolases (α-L-iduronidase EC. 3.2.1.76, β-D-glucuronidase EC. 3.2.1.31, arylsulfatase A EC. 3.1.6.1, arylsulfatase B EC. 3.1.6.1, α-D-glucosaminidase EC. 3.2.1.50, β-D-glucosaminidase EC. 3.2.1.30, and β-D-galactosidase EC. 3.2.1.33) were investigated in cells from the affected cat. The activity of α-L-iduronidase was deficient in both cultured fibroblasts and peripheral leucocytes, while the activity of the other enzymes was similar to that in normal cats. It is apparent that the pattern of GAG excretion, evidence of lysosomal storage in various tissues, evidence of defective GAG degradation in cultured fibroblasts, and the specific deficiency in activity of α-L-iduronidase in the affected cat parallel closely the findings in mucopolysaccharidosis (MPS) I of man.SpeculationThis feline model of MPS I (Hurler, Scheie, or Hurler/Scheie Syndrome) should allow advances in the understanding of the pathogenesis and approaches to therapy for this and related genetic storage diseases.

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1979

数据来源: OVID