ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

AnEscherichia coliderived somatomedin-C/IGF-I preparation (rec-IGF-I) with an amino acid sequence identical to the natural IGF-I derived from human plasma, increases body length and weight, as well as the growth of several organs of Snell dwarf mice, when administered for 4 wk. After 2 wk of treatment rec-IGF-I (22.2 μ/day) induced a significant increase over buffer treated controls, to a comparable degree as obtained with bacterially synthesized human growth hormone (bhGH; 8.4 μ/day). The weight/length ratio of rec-IGF-I and bhGH-treated dwarf mice after 4 wk of treatment were not significantly different. A significant increase over controls was obtained with both preparations. Organs with increased weights after bhGH treatment (brain; submandibular salivary glands; heart, liver, kidneys, thymus, and spleen) were also heavier after rec-IGF-I. Significance was only reached for the kidneys and the spleen and the musculus quadriceps femoris. Organs weights expressed as a percentage of body weight of bhGH and rec-IGF-I treated dwarfs were similar except for the relative weight of the heart of the bhGH group, which was significantly increased compared to the controls and the rec-IGF-I group. These data resolve the issue as to whether or not pure SM-C/IGF-I will induce growth in length and demonstrate the usefulness of recombinant IGF-I in the studies of growth regulation.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The pulmonary neuroendocrine (NE) cells, from 16 term infants dying at 1–4 days of age from birth asphyxia, were immuno stained for bombesin-like immunoreactivity by the immunoperoxidase method. The distribution and frequency of bombesin-immunoreactive NE cells were quantified morphometrically and correlated with the presence or absence of brainstem function and persistent fetal circulation (PFC). In infants with loss of brainstem function, the frequency of bombesin immunoreactive NE cells was significantly increased compared to infants with intact brainstem function,i.e.meconium aspiration with PFC. Infants with brainstem injury, with one exception, failed to develop PFC. Pathological changes in the tegmentum of the brainstem,i.e.containing the respiratory center, correlated in nine of 10 cases with loss of brainstem function. These data suggest an inverse relationship between brainstem function, release of bombesin-like peptide from the pulmonary NE cells and the functional state of the pulmonary vasculature. Intact brainstem function appears to be essential for both the release of bombesin-like peptide from the NE cells and for pulmonary vasoconstriction leading to PFC; absence of brainstem function is, on the other hand, associated with failure to release bombesin-like peptide and loss of PFC type reactivity in the pulmonary vasculature. However, it appears unlikely that bombesin itself is a direct mediator of pulmonary vasoconstriction.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

We investigated the effect of cromolyn sodium, a mast cell stabilizing agent, on the pulmonary vascular response to alveolar hypoxia in six chronically instrumented lambs aged 9 to 11 days. Each lamb was instrumented on day 6 or 7 for measurements of systemic arterial, pulmonary arterial and left atrial pressures, and pulmonary blood flow. The animals were allowed to recover from surgery at least 3 days before they were studied. Each animal was studied twice, once with a cromolyn sodium infusion and once with a normal saline infusion (placebo). These paired experiments were separated by 24 h. Physiologic measurements were made during a 1-min predose control period, after an 8-min drug or placebo infusion, and after a 15-min period of alveolar hypoxia. Cromolyn sodium infusion alone did not affect baseline cardiovascular variables. Alveolar hypoxia following placebo infusion produced an increase in pulmonary arterial pressure and pulmonary vascular resistance; these responses were blocked in the animals given cromolyn sodium prior to induction of hypoxia. These results show that cromolyn sodium blocks the pulmonary vascular response to hypoxia and provide indirect evidence that mast cell degranulation, with subsequent release of vasoactive agents, mediates the pulmonary vascular response to hypoxia in newborn lambs.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effect of verapamil and diltiazem on mechanical function was studied in the isolated arterially perfused neonatal and adult rabbit heart. The negative inotropic effect of these drugs in the newborn was significantly greater than in the adult. At concentrations 10−7M of verapamil and 10−6M of diltiazem, resting tension was significantly increased in the newborn, but not in the adult. In both age groups, verapamil and diltiazem inhibited the positive inotropy of staircase, but did not alter the inotropic effect of hyperosmolarity (116 mM mannitol). The positive inotropy of paired electrical stimulation was eliminated by these drugs in the newborn, but not in the adult. These data suggest that the neonatal heart as compared with the adult heart is more dependent on transsarcolemmal calcium influx for contraction and transsarcolemmal calcium efflux for relaxation.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

We prepared monospecific antiserum in rabbits against medium chain acyl-CoA dehydrogenase (MCAD) purified from rat liver and studied the biosynthesis of MCAD in cultured skin fibroblasts from patients with MCAD deficiency using the antibody. Cells were incubated with [35S]methionine. The labeled MCAD was immunoprecipitated using the anti-rat MCAD antiserum andStaphylococcus aureuscells and then analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We first demonstrated that antirat MCAD antibody cross-reacted specifically with human MCAD. In 13 MCAD-deficient cell lines tested, the residual MCAD activity ranged from 5–12% of the mean of normal controls, but the variant MCAD in all of these cells was indistinguishable from the normal human MCAD on the basis of molecular size, indicating that MCAD deficiency in all of these patients is most likely due to point mutation(s) in the MCAD gene.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

It was previously shown that inhibitors such as tosylamido-phenylethyl-chloromethylketone (TPCK) inhibit superoxide production by human neutrophils. These studies suggested that a chymotrypsin-like protease inhibited by TPCK was involved in the activation of the neutrophils oxidative system. In this study, we attempted to define the step in cellular activation and/or cell function inhibited by TPCK. TPCK 10−5M did not inhibit the following early events thought to be involved in the activation of oxidase. 1) f-met-leu-phe-induced activation of phospholipase C assessed by the production of inositoltris-phosphate (IP3), 2) f-met-leu-phe-induced membrane potential changes, 3) f-met-leu-phe-induced increase in free cytosolic calcium, and 4) phorbol-myristate acetate-induced protein phosphorylation in32P labeled neutrophils. We also showed that TPCK 10−5M inhibited bactericidal activity of neutrophils onStaphylococcus aureus,whereas it did not inhibit the ingestion rate of endotoxin-coated Oil red O particles. We conclude that 1) TPCK at the concentration of 10−5M inhibits superoxide production but not ingestion of Oil red O particles and 2) TPCK inhibits superoxide production at a step distal from calcium mobilization and protein phosphorylation. Radiolabeled TPCK may therefore be a useful tool to study, whether a protease is involved in the activation of the oxidative system distal to second messenger generation.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effect of passive smoking on lung histology, lung mechanics, and airway responsiveness (AR) was studied in 2-month-old lambs. Two groups of lambs were studied; 17 were exposed to cigarette smoke (CS) and 13 served as age- and sex-matched controls. Starting at 1 month of age, CS lambs had 25 daily exposures to the smoke generated from eight cigarettes. A smoking machine was constructed for the study using a Bird Ventilator. Two days prior to lung function testing, lambs were anesthetized and a Silastic balloon was placed in the pleural space for later measurement of pleural pressure. At the beginning of each study, lambs were intubated with a nasotracheal tube over a flexible fiberoptic bronchoscope. Lung mechanics (dynamic compliance, resistance of the lung, functional residual capacity) and AR were measured using a whole body plethsymograph. AR to inhaled histamine, carbachol, and citric acid was measured in each lamb on 3 separate days by giving five breaths of increasing concentrations of the aerosol in a noncumulative fashion. AR was measured both within 24 h of the final exposure to CS and at 3–7 days after CS. After the final AR was measured, lambs were anesthetized and an open lung biopsy performed. Control lambs had the same studies as CS lambs performed at an equivalent age. After 25 daily exposures to CS in 17 lambs, mean dynamic compliance was 0.024 × 0.009 liter/cm H2O, lung resistance was 2.56 × 1.32 cm H2O×liter−1s, and functional residual capacity was 0.725 × 0.234 liter. These values were not significantly different (p> 0.05) from those of the control lambs. Exposure to CS did not significantly change AR to any of the three bronchoprovocation agents tested. Histologic examination of lung tissue showed mild to moderate interstitial mononuclear cellular infiltrate, cellular debris in some airways, and occasional peribronchial inflammation in CS lambs but not in controls. Thus, passive smoking for 1 month in young lambs was not associated with a detectable alteration in lung mechanics or airway responsiveness at a time when inflammatory cells were found in the lung.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

We measured plasma estradiol levels and ovarian volumes in eight girls with precocious puberty due to McCune-Albright syndrome. Six girls had gonadotropin-independent ovarian estrogen secretion and two girls had pubertal gonadotropin levels. Mean ovarian volume in all patients was significantly greater than in normal prepubertal girls. Mean ovarian volumes of the girls with McCune-Albright syndrome overlapped the range found in girls with idiopathic central precocious puberty or central precocious puberty associated with central nervous system lesions. However, the degree of asymmetry between the right and left ovaries was significantly greater in girls with McCune-Albright syndrome. Asymmetry was due, for the most part, to the presence of large solitary cysts in the larger of the two ovaries. In the six girls with McCune-Albright syndrome and gonadotropin-independent precocious puberty, both mean ovarian volume and the degree of asymmetry between the right and left ovaries were significantly correlated with plasma estradiol. Serum follicle-stimulating hormone bioactivity was increased in two patients but did not vary with ovarian cyst size. Thyroid-stimulating hormone levels were normal but serum prolactin was slightly elevated in one of the six girls with gonadotropin-independent precocious puberty. Fluctuation in the size of unilateral ovarian cysts appears to result in changes in the plasma estradiol level, leading to advancement and spontaneous regression of secondary sexual characteristics and menses in girls with McCune-Albright syndrome. The cause of the cyst formation is unknown but may be related to periodic elevation of as yet undefined serum factors such as follicle-stimulating hormone bioactive substances.

ISSN:0031-3998    

出版商:OVID    

年代:1986

数据来源: OVID