Phagocytosis of light- and dark-adapted rod outer segments by cultured RPE cells: a reassessment

Rod outer segments (ROS) isolated from adult rat retinas are phagocytized by cultured rat retinal pigment epithelial (RPE) cells. Using a double immunofluorescent labeling procedure, we have compared the binding and ingestion of ROS isolated at different times of the day. After 2 hr of incubation, approximately 98% of the ROS are ingested, while 2% are still attached to the RPE cell surface, irrespective of the time of day or lighting conditions under which the ROS are isolated. These findings differ from those reported earlier, using a radioactive method for quantitating ROS phagocytosis (Hall, 1978).     

Accumulation of factors influencing respiratory illness in members of a national birth cohort and their offspring.

STUDY OBJECTIVE--The aim was to investigate predictors of childhood lower respiratory tract illness in two generations, and predictors of adult lower respiratory disorders in the first generation. DESIGN--Data on respiratory health and environmental factors from a national birth cohort study were examined from birth to 36 years. Data were also collected on the parents of the subjects and on the subjects' first born offspring from birth to eight years. Main outcome measures were: reports of lower respiratory tract illness before 2 years; lower respiratory tract illness of a week or more between age 20 and 36 years; regular phlegm production at 25 and 36 years; reports of wheeze or asthma at age 36 years; peak expiratory flow rate (PEFR) at age 36 years measured by nurses during home visits; and mothers' reports of lower respiratory illness in first born offspring before 2 years. SUBJECTS--Subjects were a sample of 5362 single, legitimate births taken from all those occurring in England, Wales, and Scotland in one week in 1946, and studied regularly from birth to age 43 years. Data on the subjects' parents and on their 1676 first offspring born while they were aged 19-25 years were also collected. MAIN RESULTS--Lower respiratory tract illness before 2 years fell from 25% in the population born in 1946 to 13% in their first born offspring. In those born in 1946, poor home environment, parental bronchitis, and atmospheric pollution were the best predictors of lower respiratory illness before 2 years, and these three factors and childhood lower respiratory illness and later smoking were the best predictors of adult lower respiratory tract problems. Risk factors for lower respiratory illness in the offspring were manual social class, parental and grandparental lower respiratory disease, and parental smoking. CONCLUSIONS--Risks for adult lower respiratory problems accumulated in childhood through illness, poor social circumstances, and atmospheric pollution. Smoking exacerbated early life risks and was an independent risk factor. In the offspring generation, parental smoking was a risk factor for early life chest illness, together with parental illness and low social class. Reduction of prevalence in the offspring generation was probably accounted for by improvement in home circumstances, reduced atmospheric pollution, and lower rates of parental lower respiratory illness, but current rates of smoking seem likely to prevent much further reduction in early life lower respiratory illness, and thus in this aspect of risk for subsequent adult lower respiratory problems. The accumulation of risk in childhood and adolescence for later adult problems implies a long time scale for the reduction of adult lower respiratory disorders.     

Evaluation of transesophageal Doppler detection of air embolism in dogs

The authors assessed the use of a cylindrical sensor which transceives (transmits and receives) ultrasound in a 360 degree arc mounted on a standard esophageal stethoscope catheter to detect air embolism in dogs. They used electronic circuitry developed specifically to provide a continuous analog recording of high frequency Doppler energy as well as an audible signal. They found that the esophageal Doppler sensor was easy to position. In 25 of 30 dogs, the system distinguished Doppler sounds of venous air emboli that were present either in the superior vena cava, right atrium, right ventricle, or pulmonary artery from normal cardiovascular sounds. In the remaining five animals, Doppler heart and air emboli sounds were initially of poor quality, but improved with aspiration of air from the esophagus. In another five dogs, arterial air emboli produced by left ventricular injections also were detected. The esophageal sensor was sensitive to both venous and arterial air emboli ranging from 0.05--0.2 ml of air, and the authors consistently detected repeated intravenous injections of air throughout a 5-h time period. Optimal position of the sensor for detection of venous air emboli was at the level of the superior vena cava above its junction with the right atrium. Optimal position to detect arterial air emboli introduced via a left ventricular catheter was at the level of the aortic arch. Tissue analysis of the esophagus revealed no morphologic damage due to the sensor or transmitted energy.     

Characterisation of four novel fibrillin-1 (FBN1) mutations in Marfan syndrome.

Forty-four percent of the fibrillin-1 gene (FBN1) from 19 unrelated families with Marfan syndrome was screened for putative mutations by single strand conformational polymorphism (SSCP) analysis. Four novel mutations were identified and characterised in five people, three with classical Marfan syndrome (two from one family, and one from an unrelated family), one with a more severe phenotype, and one with neonatal Marfan syndrome. The base substitutions G2113A, G2132A, T3163G, and G3458A result in amino acid substitutions A705T, C711Y, C1055G, and C1152Y, respectively. C711Y, C1055G, and C1152Y lead to replacement of a cysteine by another amino acid; the latter two occur within epidermal growth factor-like motifs in exon 25 and 27, respectively. The A705T mutation occurs at exon 16 adjacent to the GT splice site. The A705T and C711Y mutations, at exon 16 and 17, respectively, are the first documented in the second transforming growth factor-beta 1 binding protein-like motif of FBN1.     

Early time course of the acute phase protein response in man.

The rate at which the acute phase protein response occurred after both major and minor surgery was explored. Increases in the plasma concentration of C-reactive protein (CRP), alpha-1-acid glycoprotein (alpha 1 AG) and fibrinogen were not detected until 6-8 h after the initial incision. The peak concentration of CRP occurred at 48 h and that of fibrinogen at 96 h; alpha 1 AG concentrations rose rapidly until 48 h followed by little change until about 120 h. Although there was widespread variation in the concentrations of individual proteins in patients, severity of injury did not seem to have a significant effect on the time course of the change. Plasma cortisol concentration and the total white blood cell count (WBC) reached their peaks before the acute phase proteins, cortisol at 6 h and WBC at 12 h.     

Further studies of the ethanol-induced changes in pancreatic lipid metabolism

Previous in vitro studies have shown that ethanol increased de novo triglyceride synthesis in the rat pancreas. The present study extends these observations on the effects of ethanol on pancreatic lipid metabolism. Ethanol significantly stimulated [1-¹⁴C]acetate incorporation into pancreatic lipids at concentrations as low as 0.068 mM, as well as at 3.4 and 34 mM. This suggests that known metabolic pathways of ethanol oxidation are not involved in these changes. Ethanol also stimulated the incorporation of [1-¹⁴C]oleate into pancreatic triglyceride and cholesteryl ester, but not into phospholipids. These changes were less marked than those obtained with [1-¹⁴C]acetate. Furthermore, incorporation of [1-¹⁴C]palmitate into pancreatic lipid was affected even less by ethanol. Thus, ethanol-induced changes in pancreatic lipid metabolism are unlikely to be due to fatty acid esterification alone.     

Hepatic vein thrombosis (Budd-Chiari syndrome) in the microgranular variant of acute promyelocytic leukemia

The microgranular form of acute promyelocytic leukemia (APL) was described in the late 1970s and adopted by the French, American, and British classification system in the early 1980s. Morphologically, this form shows distinct differences from the classic form of APL, but clinically it shares many of the same traits. Among these is the predilection for coagulopathies, including disseminated intravascular coagulation (DIC). This DIC has been associated with one previously reported case of fatal hepatic vein thrombosis (Budd-Chiari syndrome), in association with an untreated case of APL. The authors present a case of the microgranular variant of acute promyelocytic leukemia (FAB-M3V), with autopsy and electron microscopic evidence in support. It is important to recognize this variant form of APL and its association with hepatic vein thrombosis, because any successful attempt at therapy must be instituted early in the course of the disease.