摘要:

Cultured fibroblasts from two sibs with generalized hypertonia, hepatosplenomegaly, and psychomotor retardation within the first year of life were found to have unusual morphologic features. When examined by phase microscopy, the unstained and unfixed cells contained a large number of vacuolated structures whose gross appearance resembled that of a honeycomb in the cell cytoplasm. Electron microscopy studies, following fixation, showed the “honeycombing” to be the result of numerous, closely packed, cytoplasmic, membrane-bound vacuoles. In some of these structures the remains of fibrillogranular material could be detected.Biochemical analysis of crude sonicates of these cells revealed increased levels (4–7 XN) of an acid soluble component that reacted with thiobarbituric acid. Analysis of trimethylsilyl derivatives of this material by gas liquid chromatography and mass spectrometry showed it to be indistinguishable from sialic acid (N-acetylneuraminic acid).Quantitation of this material from the cells of one of the sibs after isolation on a Dowex column yielded 39.8 nmoles of free (unbound) sialic acid per mg protein whereas normal fibroblasts had 1–2 nmoles per mg. Bound sialic acid levels were at the upper limits of normal (24.8versus11–23 nmoles per mg protein). The concentration of cytidine monophosphate-sialic acid was normal.After incubation of the patient's fibroblasts with [3H]-N-acetyl-mannosamine for 72 h, there was a 7-fold increase (compared to normal fibroblasts) in the amount of radioactivity in free sialic acid present in the acid soluble fraction. The amount of labeled, bound sialic acid in the acid-insoluble pool, however, was the same in both patient and control fibroblasts.

ISSN:0031-3998    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

The induction of abnormal embryonic development by heterologous tissue antisera has been well established. The underlying mechanism whereby such teratogenesis occurs is not known. There were implications that visceral yolk sac endoderm might be involved. Endoderm was isolated from rat visceral yolk sac of 14th day of gestation using a nonenzymic procedure. The purity of the endoderm preparation was examined by electron microscopy. The preparation contained sheets of single layer of endodermal cells with no apparent contamination by the underlying mesenchyme or basal lamina. The specificity of the antiserum was examined byin vitroimmunofluorescent localization studies. The antibodies against the endoderm localized only in the endodermal cells and some of the renal tubular cells. Intraperitoneal injection of the endoderm antiserum into 9-day pregnant rats resulted in congenital malformation, embryonic death, and fetal growth retardation. The effects of the antiserum were dose-dependent. The most frequently observed defects were anophthalmia and microphthalmia. Retarding effect of the antiserum on the growth of the embryo at the egg cylinder stage was also observed.In vivoimmunofluorescent localization studies indicated that the endoderm antibodies localized only in the endodermal cells of the visceral yolk sac placenta; no localization was observed in the visceral yolk sac mesenchyme, basal lamina, Reichert's membrane, maternal kidney tissue or the embryo proper.

ISSN:0031-3998    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Fraternal twins who had fasting hypoglycemia, hypoketonemia, muscle weakness, and hepatic dysfunction are reported. The hepatic dysfunction occurred only during periods of caloric deprivation. The surviving patient developed a cardiomyopathy. In this sibling, muscle weakness and cardiomyopathy were markedly improved by a diet high in medium chain triglycerides. There was a marked deficiency of muscle total carnitine and a mild deficiency of hepatic total carnitine. Unlike patients with systemic carnitine deficiency, serum and muscle long-chain acylcarnitine were elevated and renal reabsorption of carnitine was normal. It was postulated that the defect in long-chain fatty acid oxidation in this disorder is caused by an abnormality in the mitochondrial acylcarnitine transport.Detailed studies of the cause of the hypoglycemia revealed that insulin, growth hormone, cortisol, and glucagon secretion were appropriate and that it is unlikely that there was a major deficiency of a glycolytic or gluconeogenic enzyme. Glucose production and alanine conversion to glucose were in the low normal range when compared to normal children in the postabsorptive state. The hypoglycemia in our patients was probably due to a modest increase in glucose consumption, secondary to the decreased oxidation of fatty acids and ketones, alternate fuels which spare glucose utilization, plus a modest decrease in hepatic glucose production secondary to decreased available hepatic energy substrates.

ISSN:0031-3998    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

The absorption spectrum of serum samples from infants with bronze baby syndrome (BBS) showed spectral features typical of bilirubin (i.e., Λ max at approximately 460 nm), as well as an intense band peaking around 400 nm and a generalized broad absorbance in the near-UV and in the 600–700 nm spectral region. The two latter features were not observed in the absorption spectra of control sera; moreover, the BBS sera exhibited multiband emission spectra with maxima at 585, 619, and 670 nm. This finding indicates that the 400-nm absorption band does not reflect the presence of residual hemoglobin in the sera because hemoproteins are known to be nonfluorescent in the red region. Instead the observed emission spectra are characteristic of porphyrin compounds. The porphyrins extracted from BBS sera were analyzed chromatographically. The results of paper chromatography led to the conclusion that the two porphyrins present in the ether fraction are Cu2+-proto and Cu2+-coproporphyrin, whereas the porphyrin in the aqueous phase is Cu2+-uroporphyrin.Visible light-irradiation of diluted sera from BBS newborn infants caused an increase of the brown color of the solution corresponding with a disappearance of the typical porphyrin fluorescence and an increase of the absorbance in the near-UV and red spectral regions. Extraction of porphyrins from 15-min irradiated BBS sera showed that an essentially total destruction had occurred.In order to verify the responsibility of Cu2+-porphyrins in inducing the BBS discoloration, we irradiated 8-ml samples of serum obtained from normal cord blood in presence of Cu2+-proto, Cu2+-copro, and Cu2+-uroporphyrin, which were added at a concentration of 3.28 μg/ml. Cu2+-porphyrins were slowly destroyed and the consequent spectral changes closely resembled those observed from BBS sera from phototreated patients. The addition of equimolar bilirubin to the aqueous solution of Cu2+-porphyrins bound to albumin enhanced the first order rate constant for porphyrin photodestruction from 0.12 sec-1to 0.49 sec-1.

ISSN:0031-3998    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

The ductus arteriosus of the undisturbed fetal lamb was studied chronically by techniques that allowed direct serial measurements of the calibre of the fetal channel. When the direct actions were studied of vasoactive agents on the ductus arteriosus, prostaglandins did not dilate the vessel beyond its resting dimensions. The cyclooxygenase inhibitor, indomethacin, was a potent vasoconstrictor with a plateau of the dose-effect relationship occurring at 0.2 mg/kg. Fetuses of 95–98 days gestational age were equally sensitive to indomethacin when compared to animals near term. Although the prostaglandins, PGE1, PGE2PGF2α, PGH2, PGI2and PGG2, had no direct effect on the ductus arteriosus, PGE1, PGE2, PGH2and PGI2reversed the vasoconstrictor action of indomethacin. Autonomic nervous system mediators and blockers,i.e.,acetylcholine, atropine, norepinephrine, propranolol, phentolamine and methoxamine, had neither direct effects on the ductus arteriosus nor any influence on indomethacin-induced vasocon-striction. The same was true of angiotensin 1, angiotensin 2, blockade of conversion of angiotensin 1 to 2, serotonin, methysergide, aminophylline, adenosine, and dibutyryl cyclic AMP. Imidazole, a blocker of thromboxane synthase, had no direct effect on the ductus arteriosus, but reduced significantly the magnitude of the indomethacin constrictor action.The major finding of this investigation was the exquisite sensitivity of the ductus arteriosus to manipulations of the prostaglandin environment. The results suggest that both locally generated prostaglandins, as well as prostanoids in the circulation, may be involved in ductal patency and closure. A high degree of control is likely of the circulation of the ductus arteriosus and constriction of the fetal channel is probably the result of an active process.

ISSN:0031-3998    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

A nonlethal influenza infection [A/PC/1/73 (H3N2)] was given to infant mice to determine (1) the pathology of tracheal epithelium and lung, (2) the time course of viral shedding from the nose and lung, and (3) the subsequent development of protective immunity during adulthood.Both desquamation of the tracheal epithelium and lung pathology similar to that described in adults after influenza infection were observed in the infant. Animals infected at 3 days of age show virus shedding in 12 of 13 infant mice that persists for at least 2 days longer than in the adult. This longer duration of influenza infection did not result from either malnutrition or from intralitter transmission of virus. Recovery from virus shedding in both the upper and lower airway occurred in the absence of detectable serum antibody in six of seven mice. Infants that recover from infection, when rechallenged during adulthood, manifest complete protection in 11 of 13 mice after nonlethal challenge and no mortality after lethal challenge.

ISSN:0031-3998    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Autopsy samples were obtained from a 12.5-year-old girl who died with a neurologic disorder consisting of myoclonus, myoclonic epilepsy, spasticity, strabismus, and mild mental retardation but no hepatosplenomegaly. Studies in leukocytes, cultured skin fibroblasts, brain, liver, and spleen of this patient revealed glucosylceramide β-glucosidase (EC 3.2.1.45, glucocerebrosidase) activity about 10% of controls, and well in the range found in samples from Gaucher disease patients. Extraction of the lipids from liver and spleen with chloroform-methanol (2:1) did not show accumulation of glucosylceramide or other lipid. Examination of the lipids in brain by high performance liquid chomatography revealed the presence of glucosylceramide, which is not found in brain samples from controls. Pathologic examination of the liver and spleen revealed no evidence of Gaucher disease. The brain showed many degenerative lesions and loss of neurons. There was no complementation of glucocerebrosidase activity when the cells from this patient were hybridized with cells from patients with Type 1 or Type 2 Gaucher disease. The reason for the lack of glucosylceramide storage in the liver and spleen has not been determined.

ISSN:0031-3998    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

The acute systemic and neuropathologic effects ofE. coliendotoxin were determined in neonatal dogs. Administration of sublethal (LD0), moderate (LD50), or lethal (LD100) doses of endotoxin produced significant arterial hypotension, metabolic (lactic) acidosis, and hypoglycemia. Neuropathologic changes consisted of widespread inflammation in both grey and white matter; however, necrotic lesions were found only in forebrain white matter.

ISSN:0031-3998    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Two patients with acrodermatitis enteropathica had abnormal lysosomal inclusion bodies in the intestinal epithelial cells while in relapse but fewer smaller ones after zinc therapy. The third patient with acrodermatitis enteropathica in remission on zinc therapy had no inclusion bodies. The smaller inclusion bodies were similar to those found in coeliac disease.

ISSN:0031-3998    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

The purpose of this study was to investigate the effect of severe “stress” on neonatal neutrophil (PMN) phagocytosis, and to compare the ability of neonatal and adult PMNs to ingest [3H]-labeled type Ic group B streptococcus (GBS). Three patient populations were studied: healthy and “stressed” newborn infants and healthy adults. Severe “stress” was defined as an acute, noninfectious respiratory illness, sepsis or severe birth asphyxia; 94% of these infants required assisted ventilation. Radiolabeled GBS was opsonized with 5% adult serum, and incubated with PMN monolayers adherent to glass coverslips. Bacterial uptake was determined at 0, 40, 60, and 80 min and expressed as counts per min/106PMNs. Neutrophis from healthy and “stressed” newborn infants demonstrated a significant increase in bacterial uptake with time. Adult controls also showed a significant increase in phagocytosis through 60 min, but not during the 60–80 min time period. PMNs from “stressed” and healthy infants demonstrated enhanced bacterial uptake when compared to adults at 40, 60, and 80 min. There were no significant differences in bacterial ingestion between “stressed” and healthy infants. Radiolabeled GBS uptake did not correlate with birth weight, study age, Apgar scores, or peripheral leukocyte count for the “stressed” newborn population. Neutrophils from healthy and “stressed” newborn infants thus demonstrate increased phagocytosis of GBS when compared to healthy adults.

ISSN:0031-3998    

出版商:OVID    

年代:1983

数据来源: OVID