摘要:

Fibronectin (FN), a glycoprotein component of the extracellular matrix, plays a role in tissue morphogenesis and tissue-specific differentiation through its effects on cell adhesion, cell shape, and cytoskeletal organization. Immunohistochemistry has been used to show that during lung development FN deposition changes, yet the cell-specific sites of pulmonary FN synthesis have not been determined. Because cellular FN synthesis is reflected by FN mRNA abundance, we performedin situhybridizations to identify pulmonary tissue with the capacity to synthesize FN. Bothin situmRNA hybridization and immunohistochemical staining were performed on tissue sections from lungs of adults and late gestation fetal and neonatal rabbits. In adults, FN transcripts and immunostaining were clearly seen in endothelial cells, smooth muscle cells, and chondrocytes. During lung development, FN transcripts were virtually ubiquitous except in airway epithelium. There was a gradual decrease in FN mRNA abundance with advancing fetal age, but low levels of FN mRNA persisted in neonatal and adult lungs. In contrast, parenchymal immunostaining increased throughout fetal development and remained elevated in the newborn. FN immunostaining was lower in adult lung. In all tissues examined, airway epithelial cells contained no FN transcripts above background. However, immunostaining was detected in airway basement membrane zones and on luminal surfaces of some epithelial cells. The lack of FN transcripts in airway epithelial cells suggests that FN synthesis does not normally occur in this cell type and that its associated FN immunostaining is from another source. The colocalization of FN mRNA and protein in pulmonary endothelial cells, smooth muscle cells, and chondrocytes in adults strongly suggests that these cells are sites of FN synthesis.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The stretch-induced myogenic response (MR) of large-capacitance pulmonary arteries were studied in normal and pulmonary hypertensive fetuses as well as normal newborn and adult sheep. Pulmonary hypertension in the fetus was induced by ligation of the ductus arteriosus for 12 d. The MR was obtained by stretching the vessel segmentsin vitrofrom their resting diameter (no load) to the diameter at which the muscle fibers were at optimal length (Lo), and the response was measured as a percentage of force obtained after supramaximal electrical stimulation (Po). In five control and four pulmonary hypertensive fetuses, the MR was also obtained after a stretch of 140% of Lo. The pulmonary hypertensive fetal arteries had a lower stress (1.3 ± 0.4versus4.0 ± 0.5 mN/mm2;p< 0.001) and shortening capacity compared with the fetal control (5.1 ± 1.6versus9.9 ± 0.8% of Lo;p< 0.01). The MR was observed in 21% of the control and 30% of the experimental fetuses, and it was of greater magnitude in the latter (14.8 ± 1.9 of Poversus34.3 ± 2.5%, respectively;p< 0.01). When stretched to 140% of Lo, the MR was also greater in the experimental (514 ± 148% of Po) than the control fetuses (142 ± 68;p< 0.05). Postnatally, the MR was present in 67% of the newborn and 15% of the adult pulmonary artery segments, and the response was greatest in the newborn (23.1 ± 4.2% of Po) compared with the adult (2.3 ± 0.8;p< 0.01). These data indicate that the stretch-induced MR of large-capacitance pulmonary arteries of the sheep shows significant developmental differences postnatally and is greatly enhanced in the fetus after pulmonary hypertension. We speculate that large-capacitance arteries play a role in the control of pulmonary vascular resistance in pulmonary hypertension as a result of wall stiffness changes in response to intravascular pressure-induced MR.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

During growth and development, dietary intake changes from being predominantly liquid in the newborn period to mixed solid liquid meals. These alterations in diet vary the functional demands placed on the stomach. It has been shown that, during development, smooth muscle of the stomach undergoes changes in the mechanism responsible for the contractile process. In this study, we have investigated the possibility that there are structural changes in two of the major proteins that are responsible for generation of force during smooth muscle contraction: actin and myosin. Actin and myosin were identified in newborn kittens (1 wk old) and adult gastric smooth muscle using one-dimensional SDS-PAGE. Although both the antrum and fundus of the kitten have significantly smaller total amounts of actin and myosin per mg protein than the adult, the ratio of actin to myosin is not significantly different between the age groups. Two different myosin heavy chain (MHC) isoforms, MHCl (205 kD) and MHC2 (200 kD), were identified in all tissues. The relative amount of MHC1 remained constant during maturation of the stomach. We observed an increase in the amount of MHC2 in the adult, which resulted in a decreased ratio of MHC1 to MHC2 in the adult. We postulate that the decreased quantity of actin and myosin in the kitten stomach and the observed changes in the ratio of the MHC isoforms are related to changes in the gastric motor that occur during growth and development.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The development of brush-border enzymes and the possible regulatory role of cortisol were investigated in the small intestine of the fetal and neonatal pig. With the sows under pentobarbitone anesthesia, osmotic minipumps containing either saline or cortisol were inserted s.c. into 25 fetuses from 10 pregnant sows (82–96 d gestation). Six d later, the infused fetuses were removed by cesarean section and samples of the proximal, middle, and distal intestine taken for analysis. Samples were also obtained from 48 piglets that did not undergo an operation (controls) and that were removed at intervals from 82 d gestation until term (114 ± 2 d). In the proximal and middle intestine, the mean levels of lactase-phlorizin hydrolase (EC 3.2.1.23–62), maltase-glucoamylase (EC 3.2.1.20), aminopeptidase N (EC 3.4.11.2), and aminopeptidase A (EC 3.4.11.7) increased during the last 10–15 d before term, correlated positively with log10plasma cortisol values, and were higher in cortisol-infused than in saline-infused fetuses (p< 0.05). Activity of sucrase-isomaltase (EC 3.2.1.48–10) was low in fetal pigs, and this enzyme and dipeptidyl peptidase IV (EC 3.4.14.5) were not significantly affected by fetal age or exogenous cortisol. Maltase (EC 3.2.1.48–10 and EC 3.2.1.20) activity was significantly decreased in the middle and distal intestine of cortisol-infused fetuses. The results suggest that the prepartum rise in endogenous cortisol secretion stimulates the prenatal expression of certain brush-border enzymes in the pig small intestine at this critical time. However, the effects of cortisol on the developing intestine were highly idiosyncratic for particular enzymes and intestinal regions.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The incidence and prevalence of celiac disease vary internationally. We studied the incidence of identified cases of childhood celiac disease in six Dutch provinces that cover 47.9% of the surface area and 67.6% of the total population of The Netherlands. Children with celiac disease aged 0–14 y, diagnosed from January 1975 to January 1991, were traced by1) contacting all pediatricians in this area,2) examining the data of the Dutch National Medical Registration, and3) investigating the membership records of the Dutch Celiac Disease Society. These data were cross-checked by the Dutch Network and National Database of Pathology. Of the 97.9% of pediatricians who answered our inquiry, 46.1% were treating celiac patients. A total of 342 celiac patients were identified. Informed consent that permitted examination of their medical files was given by 97.3% of the parents of the celiac children. The mean crude incidence rate of diagnosed childhood celiac disease, calculated per 1000 live births per year, was 0.18. However, a significant increase in reported incidence was demonstrated from 0.10 in 1976 to 0.32 in 1990. The best estimate, for the years 1985–1990, is 0.22/1000 live births, which is much lower than in most European countries.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

It has been demonstrated that the level of serum copper unbound to ceruloplasmin (loosely bound copper) is increased in Wilson's disease, although the total serum copper concentration is usually low, reflecting a low ceruloplasmin level. To assess the contribution of free radical reactions catalyzed by nonceruloplasmin copper to the development of complications in this disease, we investigated copper and antioxidant status in four untreated patients who had hepatic dysfunction with or without hemolytic anemia and made a comparison with five patients controlled on penicillamine therapy and 19 age-matched healthy children. We found that loosely bound copper in plasma measured by the phenanthroline assay was detectable in three of four untreated patients with Wilson's disease, but was not detectable in the patients during therapy or in the healthy controls. Among the various antioxidants, the ascorbate and urate levels were markedly reduced before treatment (mean ± SD, 23 ± 16 μM for ascorbate and 90 ± 59 μM for urate) compared with the values in the patients during treatment with penicillamine (67 ± 19 and 302 ± 78 μM,p< 0.05) and in control children (60 ± 8 and 254 ± 48 μM,p< 0.05). We also demonstrated that the plasma concentration of allantoin, an oxidation product of uric acid and a possible marker of radical generationin vivo, was markedly elevated in the untreated patients (11.0 ± 1.8versus4.3 ± 0.5 μM in patients on therapy and 6.5 ± 0.8 μM in controls,p< 0.05). The low plasma urate level together with the elevation of allantoin were thought to be responsible for the degradation of uric acid as a sacrificial antioxidant. In contrast, the plasma levels of α-tocopherol and thiobarbituric acid reactive substances did not differ in these three groups. The value of the total radical-trapping antioxidant parameter was reduced in the patients before the initiation of therapy (372 ± 146versus942 ± 79 μM in patients on therapy and 856 ± 104 μM in controls,p< 0.05), and this was mainly attributed to the depletion of ascorbic acid and uric acid. These findings suggest that the elevation of loosely bound copper leads to transition metal catalyzed free radical reactions in the aqueous phase of plasma, which may play a role in the clinical complications of Wilson's disease.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Taurine is a β-sulfonic amino acid that serves as a nutrient important for developing brain and retina and as an osmolyte in the medullary collecting duct. The activity of the taurine transport system is regulated by substrate supply and by the external osmolality; these two stimuli induce changes in taurine transport. Increased medium osmolality (500 mosmol) stimulates taurine uptake into MDCK cells but not LLC-PK1 cells. The enhanced taurine uptake that occurs in response to hyperosmolality is localized primarily to the basolateral surface of MDCK cells, whereas the adaptive response to medium taurine concentration is expressed on both the apical and the basolateral surfaces of both cell lines. The response of MDCK cells to medium osmolality requires protein synthesis and RNA transcription and is expressed in the presence of microtubular toxins. When cell monolayers were loaded with taurine by incubation in high-taurine medium before increasing medium osmolality, the expected increase in taurine uptake was blunted. Similarly, increased external β-alanine (500 μM) also prevented the anticipated increase in taurine accumulation in response to hypertonicity; aminoisobutyric acid and betaine (500 μM) partially prevented the increase in taurine transport after hypertonicity, whereas L-alanine had no effect. The concentration of taurine or structurally similar analogs in the external medium might modify the response of taurine accumulation after exposure to hypertonic medium, in that taurine-replete cells behave differently than taurine-depleted cells. These studies indicate that there are at least two distinct mechanisms involved in the regulation of taurine transport: external taurine concentration and medium osmolality, with taurine concentration seeming to be the predominant stimulus. Thus, the changes in cell taurine transport depend on the physiologic stimulus as well as the cell studied, a phenomenon that might be related to the renal tubular site of origin.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The rate of evaporation from the skin (g/m2/h) was measured in 12 full-term and 16 preterm infants (gestational age 25–34 wk) both during incubator care and when nursed under a radiant heater. The method for evaporation rate measurement is noninvasive and based on determination of the water vapor pressure gradient close to the skin surface. Measurements were first made with the infant nursed in an incubator with a controlled environment with respect to humidity, temperature, and air velocity. The measurements in the term infants were performed at an ambient relative humidity (RH) of 50%, and in the preterm infants first at 50% and subsequently at 30–40%. Evaporation rate was then measured with the infant nursed under a radiant heater. In term infants, mean evaporation rate was 3.3 g/m2/h during incubator care (RH 50%) and 4.4 g/m2/h during care under the radiant heater. In preterm infants, the corresponding values were 15.5 g/m2/h in the incubator at RH 50%, 16.7 g/m2/h at RH 30–40%, and 17.9 g/m2/h under the radiant heater. It is concluded that the evaporative water loss from the skin depends on the ambient water vapor pressure, irrespective of whether the infant is nursed in an incubator or under a radiant heater. The higher rate of evaporation during care under a radiant heater is due to the lower ambient water vapor pressure and not to any direct effect of the nonionizing radiation on the skin.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

This review is based on a lecture given in connection with the 1994 Nutricia Foundation Award. It describes how recent research findings in infant dietary energy requirements have provided a firm quantitative basis for the widely quoted pediatric view that exclusive breast-feeding should provide sufficient nourishment for the average child until 4–6 mo of age.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Disorders of the CNS are the major causes of morbidity and mortality observed in untreated subjects with phenylketonuria (PKU). A method to measure cerebral concentrations of phenylalanine (Phe)in vivowould greatly enhance the ability to investigate both the pathophysiology and the efficacy of therapy of this aminoacidopathy. Twelve image-guided localized proton nuclear magnetic resonance spectroscopic studies were performed in seven subjects with PKU using pulse sequences optimized to detect the aromatic protons of Phe. Ten control studies were also performed using a 2.1-Tesla Bruker Biospec spectrometer. Plasma Phe was measured at the time of the spectroscopic examination in the PKU patients. A Phe signal was observed in all 12 studies performed on the group with PKU, and in five studies cerebral Phe concentrations were measured to be 480 to 780 μmol/g. Plasma Phe concentrations were 0.7 to 3.3 mM (10.8 to 54.8 mg/dL) in the subjects with PKU. Human cerebral Phe concentrations can be measured noninvasively using proton nuclear magnetic resonance spectroscopy. A simultaneous measure of Phe and several other cerebral metabolites is obtained with this innovative technology. Adaptations of this technique can be used to investigate PKU and other neurometabolic disorders with modifications of current clinical magnetic resonance imaging systems.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID