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Showing papers by "Boston Children's Hospital published in 1976"


Book ChapterDOI
01 Jan 1976
TL;DR: In all geographic areas it is now clear that RSV is the major cause of bronchiolitis and pneumonia in infants and young children, and there are many pressing questions concerning the pathogenesis of serious life-threatening disease of the lower respiratory tract produced by this virus during early infancy.
Abstract: Respiratory syncytial virus (RSV) was first isolated from a chimpanzee with common-cold-like illness.(53a) Shortly thereafter, the virus was recovered from young children with severe lower respiratory tract disease in Baltimore. (11,16) Since its initial isolation from infants with respiratory disease almost 20 yr ago, RSV has emerged as the major lower respiratory tract pathogen of infancy and early childhood throughout the world. (3,15,16,69) In all geographic areas it is now clear that RSV is the major cause of bronchiolitis and pneumonia in infants and young children. RSV presents a special challenge to the epidemiologist since this virus exhibits a pattern of infection and disease unlike that of any of the other known respiratory tract viral pathogens. Unanswered are many pressing questions concerning the pathogenesis of serious life-threatening disease of the lower respiratory tract produced by this virus during early infancy.

1,161 citations


Journal ArticleDOI
10 Jun 1976-Nature
TL;DR: In foetal monkey brain neuronal projections carrying input from the two eyes initially overlap; they segregate during the second half of gestation and become fully separated in subcortical visual centres and partially separated in the cortex three weeks before birth and thus before visual experience.
Abstract: In foetal monkey brain neuronal projections carrying input from the two eyes initially overlap; they segregate during the second half of gestation and become fully separated in subcortical visual centres and partially separated in the cortex three weeks before birth and thus before visual experience.

663 citations


Journal ArticleDOI
TL;DR: There is a marked effect of PEG concentration on cell hybridization, and there seem to be inherent differences between cells in terms of the extent of cell fusion induced by PEG.
Abstract: Modifications in the techniques for the induction of mammalian somatic cell hybridization by polyethylene glycol (PEG) have led to procedures that are rapid, simple, and effective. The basic improvements, for both monolayer and suspension fusions, are a short exposure to PEG and a rapid dilution of PEG following treatment. There is a marked effect of PEG concentration on cell hybridization, and there seem to be inherent differences between cells in terms of the extent of cell fusion induced by PEG.

492 citations


Journal ArticleDOI
07 May 1976-Science
TL;DR: Regardless of sex, early maturing adolescents performed better on tests of verbal than spatial abilities, the late maturing ones showed the opposite pattern, and Those maturing late were more lateralized for speech than those maturing early.
Abstract: Regardless of sex, early maturing adolescents performed better on tests of verbal than spatial abilities, the late maturing ones showed the opposite pattern. Those maturing late were more lateralized for speech than those maturing early. Sex differences in mental abilities, it is argued, reflect differences in the organization of cortical function that are related to differential rates of physical maturation.

376 citations


Journal ArticleDOI
TL;DR: For monolayer fusions, PEG 1000 at 50% seems to be the optimal combination of PEG molecular weight and concentration, in terms of both efficiency of hybridization and relative insensitivity to dilution effects.
Abstract: The effects of polyethylene glycol (PEG) molecular weight and concentration on mammalian cell hybridization were studied. The peak hybridization-inducing activity with all grades of PEG from 400–6000 was found to occur in the concentration range of 50–55%. However, changes in concentration were seen to have different quantitative effects with different grades of PEG. For monolayer fusions, PEG 1000 at 50% seems to be the optimal combination of PEG molecular weight and concentration, in terms of both efficiency of hybridization and relative insensitivity to dilution effects.

277 citations


Journal ArticleDOI
TL;DR: In two hearts with situs solitus the aortic valve was right-sided with respect to the pulmonary valve, important for both diagnosis and nomenclature.
Abstract: The detailed anatomy of the heart is described in 32 autopsy cases of congenitally corrected transposition of the great arteries.Tis condition is defined as the combination of atrioventricular (A-V) discordance and transposition of the great arteries. Examples of primitive (single) ventricle with "inverted" (that is, left-sided in situs solitus) outlet chamber are excluded. Six hearts with A-V discordance and pulmonary atresia are described in an appendix. In 29 cases of corrected transposition the heart was in situs solitus; in 3 it was in situs inversus totalis. Only 5 of these 32 hearts had no potential for intracardiac shunting. Anomalies of the tricuspid valve (91 percent of cases), ventricular septal defect (78 percent) and pulmonary outflow tract obstruction (44 percent) occurred with sufficient frequency to be considered part of the basic malformation and are described in detail. The precise anatomy and disposition of the A-V valve tension apparatus, the coronary arteries and the conducting tissues are described with special reference to possible surgical approaches for repair of the anomalies. In two hearts with situs solitus the aortic valve was right-sided with respect to the pulmonary valve. This finding is important for both diagnosis and nomenclature.

248 citations


Journal ArticleDOI
TL;DR: The name glutaric aciduria 'type II' is proposed for the patient's disease, tentatively supposed to be localized at the level of the metabolism of a range of acyl-CoA compounds.

223 citations


Journal ArticleDOI
01 Apr 1976-Nature
TL;DR: A BUdR technique is reported which enables the detection of SCEs formed in spermatogonial cells of intact mice and is utilised to demonstrate a several-fold increase in the sister chromatid exchange frequency in mouse sperMatogonia after injection of the animals with small amounts of mitomycin C.
Abstract: SPERMATOGONIA, as stem cells of male gametes1,2, constitute a highly relevant system for studying the genetic hazards of potential mutagens. Gross chromosome aberrations in spermatogonia have been used as a gauge of the genetic damage induced in animals exposed to agents such as mitomycin C (refs 3–5). Sister chromatid exchanges (SCEs) formed in response to DNA damage constitute even more sensitive indices of the impact of alkylating agents and other clastogens on chromosomes6–8. Analysis of SCE induction in cultured cells has been greatly facilitated by techniques in which substitution of DNA with the base analogue 5-bromodeoxyuridine (BUdR) is detected either with fluorescent dyes9,10 or by modified Giemsa procedures11–13. This approach has so far been limited to in vitro trials, with the exception of one system14 in which SCEs were visualised in chromosomes of chick embryos after exposure to BUdR in ovo. We report here a BUdR technique which enables the detection of SCEs formed in spermatogonial cells of intact mice. As a prototype of a general in vivo mutagenesis test, this procedure has been utilised to demonstrate a several-fold increase in the sister chromatid exchange frequency in mouse spermatogonia after injection of the animals with small amounts of mitomycin C.

149 citations


Journal ArticleDOI
TL;DR: In 129 of 140 attempts, human skin cells were successfully cultured on the dermal collagen bed of sterile, dead pigskin, and multiplication of epithelial cells, rather than migration, was indicated by mitotic figures in colchicine-treated cultures and by DNA synthesis.
Abstract: In 129 of 140 attempts, human skin cells were successfully cultured on the dermal collagen bed of sterile, dead pigskin. Diploid epithelial cells grew selectively on the collagen bed; fibroblasts grew on the glass surfaces of the culture dishes. The cultures could be subdivided physically up to six times at a 1:2 split ratio, but at least 24 to 48 cell generations were produced over the months the cells could be carried. Much of the cell multiplication resulted in maturation into distinct basal, squamous, granular, and keratinized cell layers. The cultured cells were considered epithelial because of their shape, possession of intercellular bridges, desmosomes and tonofibrils, and because they formed maturating epithelium in vitro and upon transplantation back to the original human donor. As the cells grew they digested the pigskin collagen, thus producing clear zones that could be used to monitor and quantitate cell growth. Multiplication of epithelial cells, rather than migration, was indicated by mitotic figures in colchicine-treated cultures and by DNA synthesis.

140 citations


Journal ArticleDOI
TL;DR: Rod outer segment disc shedding and phagocytosis by the pigment epithelium has been studied by light microscopy in sections from plastic-embedded eyes taken from albino rats at different times of the day and night.

139 citations


Journal ArticleDOI
TL;DR: This investigation involves the manometric study of the esophagus in the newborn, as well as maturation of the pressure barriers of this esophageal segment and the influence that certain factors have on it.

Journal ArticleDOI
TL;DR: Prolonged exposure of the neonatal kitten to a lipopolysaccharide results in a telencephalic leucoencephalopathy characterized by astrogliosis and necrosis.

Journal ArticleDOI
TL;DR: The presence of Gla in soft tissue calcifications is a potentially significant finding, especially in view of its known calcium and phospholipid binding properties as discussed by the authors, since a γ-carboxyglutamic acid-containing protein is normally present in bone and absent in unmineralized tissues.

Journal ArticleDOI
TL;DR: A pediatric treatment program for encopresis was established in a large medical center and consisted of counseling and education, initial bowel catharsis, a supportive maintenance program to potentiate optimum evacuation, retraining, and careful monitoring and follow-up.
Abstract: A pediatric treatment program for encopresis was established in a large medical center. This consisted of counseling and education, initial bowel catharsis, a supportive maintenance program to potentiate optimum evacuation, retraining, and careful monitoring and follow-up. A group of 127 children received care for this problem. At the end of one year, outcome data were obtained on 110 patients. Of these, 51% had not had "accidents" for more than six months. Another 27% showed marked improvement and were having only rare episodes of incontinence. 14% of these children showed some improvement, but continued to have incontinence, while 8% showed no improvement whatsoever during the treatment year. These four outcome groups were compared with respect to a large number of demographic, developmental, psychosocial, and clinical variables.

Journal ArticleDOI
TL;DR: The combination of centromere staining asymmetry and sister chromatid differentiation at metaphase permits unambiguous determination of the number of replications in BrdU and dT (deoxythymidine) undergone by individual cells.
Abstract: BrdU (5-bromodeoxyuridine)-33258 Hoechst methods have been adapted for in vivo analyses of replication kinetics, sister chromatid differentiation and sister chromatid exchange (SCE) formation in mice. Sufficient in vivo BrdU substitution for cytological detection was effected with multiple intraperitoneal injections of the analogue. The combination of centromere staining asymmetry and sister chromatid differentiation at metaphase permits unambiguous determination of the number of replications in BrdU and dT (deoxythymidine) undergone by individual cells. Late-replicating regions in marrow and spermatogonial chromosomes are highlighted by bright fluorescence after sequential incorporation of BrdU followed by dT during a single DNA synthesis period. SCEs are analyzed in marrow and spermatogonial metaphases after successive complete cycles of BrdU and dT incorporation. Significant induction of SCE was observed with both mitomycin C and cyclophosphamide; the latter drug requires host-mediated activation to be effective. In meiotic metaphase cells harvested two weeks after BrdU incorporation, satellite DNA asymmetry, sister chromatid differentiation and SCE could be detected in a few chromosomes, most frequently the X and the Y.

Journal ArticleDOI
TL;DR: The results indicate that a single symptomatic exposure or a series of subclinical exposures to sarin or dieldrin can alter the frequency spectrum of the spontaneous EEG for up to 1 yr.

Journal ArticleDOI
TL;DR: The laminar and cellular structure of retrosplenial cortex in the rhesus monkey was studied with Nissl stained and rapid Golgi impregnated tissue and the results were used to evaluate morphological features of a cortical transition zone.
Abstract: The laminar and cellular structure of retrosplenial cortex in the rhesus monkey was studied with Nissl stained and rapid Golgi impregnated tissue and the results were used to evaluate morphological features of a cortical transition zone. The granular layer of retrosplenial granular cortex is composed primarily of small, densely packed, star pyramidal cells. These cells branch within the granular layer itself, while the apical dendrite enters layer I where it branches infrequently or not at all. This cell type is similar to the star pyramid first described by Lorente de No except in its areal and laminar distribution. Cytoarchitectonic observations of retrosplenial agranular cortex show that, although this area is relatively “agranular” in comparison to other cortical areas, it does possess an incipient layer II and layer IV. These layers are composed mainly of small and medium sized pyramidal cells, but many non-pyramidal cell types were found in these and other layers in this area in rapid Golgi preparations. Stellate cells with beaded or smooth, lightly spinous dendrites were found throughout layers I–IV, while fusiform cells with smooth or very lightly spinous dendrites appear in layers III–VI. Areas surrounding retrosplenial cortex in the posterior cingulate region were also evaluated in Nissl and Golgi preparations including the indusium griseum, subiculum (dorsal to the corpus callosum) and area 23. The laminar and cellular constituents of retrosplenial cortex were then evaluated in the context of cortical architectonic transition. The transition from one cellular layer in the indusium griseum to five cellular layers in area 23 is made by the addition of layers II, III, IV and VI in retrosplenial cortex to the one ganglionic layer of the indusium griseum and subiculum. Besides the addition and subdivision of layers in retrosplenial cortex, two aspects of cell morphology were found to change in this region. First, the structure of pyramidal cells progressively changes from those in the indusium griseum which have predominently round or oval somata and a preponderance of apical and few basal dendrites to those in layer V of retrosplenial cortex and area 23 which have pyramidal shaped somata and a great number of basal dendrites which branch frequently and spread horizontally for hundreds of microns. Second, there is a change in the number and distribution of non-pyramidal cell types. Evidence was not found that the indusium griseum, dorsal subiculum or layer V of retrosplenial granular cortex contain a significant number of stellate or fusiform cells. At the retrosplenial granular/agranular border, though, these cells gradually begin to constitute a greater proportion of the cell population and in area 23 form a major component of layer IV. Since these laminar and cellular changes are similar, in part, to those observed by previous investigators as characteristic of ascending phylogenetic and ontogenetic development, cortical architectonic transition represents another dimension along which the cortex progressively elaborates.

Journal ArticleDOI
TL;DR: Thorough perfusion of rat and rabbit kidneys to remove blood contamination does not remove the γ-carboxyglutamate containing protein(s), which appear to be localized in the cortex, and incubation of kidney microsomes with [14C]NaHCO3in vitro results in the post-translational formation of protein bound [ 14 C]-γ- carboxy glutamic acid.

Journal ArticleDOI
TL;DR: It is concluded that a low absolute granulocyte count in severe NEC is associated with a poor prognosis and thrombocytopenia is a significant problem insevere NEC and may occur with or without evidence of fulminant intravascular coagulation.

Journal ArticleDOI
13 May 1976-Nature
TL;DR: It was found that the blunted ventilatory response to hypoxia and large lung volumes developed gradually after birth over a period of many years, and that the phenomena were at least partly reversible at sea level.
Abstract: A VARIETY of adaptive mechanisms which aid in the physiological adjustment to the hypoxic environment of altitude have been reported in man1. Although visitors to high altitudes increase ventilation in response to environmental hypoxia, natives in the Andes and Himalayas show a blunted or absent ventilatory response to acute hypoxia both at rest and during exercise2–5. Adult high altitude natives in the Andes have larger lungs with a greater gas exchange surface, as judged by physiological tests of lung volume and diffusing capacity, than sea level natives or short term visitors at altitude6–9. Whether these respiratory adaptations in man are determined solely by environment or relate to genetic traits is uncertain. The age at which these pulmonary adaptations to hypoxia occur is not known, neither is it certain whether migrants to and from high altitude reversibly acquire these physiological changes. To investigate further the mechanism of pulmonary adaptations to chronic hypoxia and to clarify the position of genetic factors in this process, we undertook an expedition to Peru from April to August 1975. Control of ventilation and lung volumes were studied in different age groups, from neonatal period to adulthood, both at high altitude and sea level. It was found that the blunted ventilatory response to hypoxia and large lung volumes developed gradually after birth over a period of many years, and that the phenomena were at least partly reversible at sea level. The results showed that the adaptive response in respiratory physiology were determined by environmental rather than genetic factors.

Journal ArticleDOI
TL;DR: Results further substantiate the direct post-synaptic inhibitory nature of GABA, 5-HT and NE, and the noradrenergic pathway from locus coeruleus to Purkinje cells, and consistent inhibitory responses to cyclic AMP in the weaver support the previously hypothesized role of cyclic Amp in the post- synapse inhibitory response to NE.

Journal ArticleDOI
TL;DR: Observations showed that mammary tumor growth was depressed by a fat-free or saturated-fat diet and enhanced by dietary linoleate and suggested that the growth rate was related to the arachidonate content rather than the linolesate content of the tumors.
Abstract: Three-month-old C3H female mice were given injections of 5-mg pieces of mammary adenocarcinoma and were then fed diets that either were fat free or contained saturated fat (15% hydrogenated cottonseed oil) or linoleate (1-15% corn oil). After 6 weeks, the tumors in mice fed the linoleate diet weighed 3-4 times more than those in mice fed the fat-free or saturated-fat diets. Despite a linoleate-free diet, tumors contained appreciable amounts of linoleate and arachidonate (approximately 2 and 9% of the total fatty acids, respectively). When the level of dietary corn oil was increased from 1 to 15%, the linoleate content of the tumors increased from 4 to 18% of the total fatty acids. However, in these instances, the tumor arachidonate levels increased to maximum values even when the 1% corn oil diet was used. These observations showed that mammary tumor growth was depressed by a fat-free or saturated-fat diet and enhanced by dietary linoleate. Furthermore, they suggested that the growth rate was related to the arachidonate content rather than the linoleate content of the tumors.

Journal ArticleDOI
TL;DR: In this article, the authors evaluated the psychological impact of cystic fibrosis on adolescents and young adults and identified four sources of psychological stress, leading to emotional disturbance: altered physical appearance causing distorted body images and denial of sexuality, strained interpersonal relationships resulting in isolation and mental strain, conflicts in upbringing, and increased awareness of the future and of death.

Journal ArticleDOI
TL;DR: Fluorescence analysis permits identification of late replicating X chromosomes in a very high proportion of cells and affords a high resolution method for determining the interchange points of X-X and X-autosome translocations.
Abstract: BrdU-33258 Hoechst techniques have been used to characterize DNA replication patterns in lymphocytes from human females with supernumerary or structurally abnormal X chromosomes. Fluorescence analysis permits identification of late replicating X chromosomes in a very high proportion of cells and affords a high resolution method for determining the interchange points of X-X and X-autosome translocations. Asynchrony among terminal replication patterns of multiple late replicating X chromosomes within an individual cell can occasionally be demonstrated. The arms of isochromosomes usually exhibit symmetrical fluorescence patterns, with replication terminating in bands Xq21 and Xq23 (predominant pattern) or in bands Xq25 and Xq27 (alternative pattern) in both arms. In the vast majority of lymphocytes containing a balanced X-13 or X-19 translocation, the normal X is late replicating. However, DNA synthesis in the translocation products occasionally appears somewhat delayed relative to that expected for an early replicating X, consistent with possible position effects on replication kinetics.


Journal ArticleDOI
TL;DR: A new classification for aortic valve atresia is presented based on the status of the ventricular septum, which in turn appears to determine the size of the left ventricular cavity.
Abstract: Certain clinical and morphologic observations are described in 73 necropsy patients with aortic valve atresia. The mean age at death was 5 days; 80 percent died during the first week of life, and 70 percent were boys. Of the 73 patients, 69 (95 percent) had a hypoplastic left ventricle with intact ventricular septum and either an atretic (25 patients) or hypoplastic (44 patients) mitral valve. The other four patients had a well developed left ventricle with one or more defects in the ventricular septum and either an atretic (one patient) or well developed (three patients) mitral valve. Review of previous reports on aortic valve atresia disclosed that a well developed left ventricle or ventricular septal defect in association with absence of the aortic valve was extremely rare. A new classification for aortic valve atresia is presented based on the status of the ventricular septum, which in turn appears to determine the size of the left ventricular cavity. The predilection for male subjects for all types of aortic valve disease, including atresia, is emphasized.

Journal ArticleDOI
TL;DR: For some age groups a steady rise in incidence of trisomy 21 cases was found throughout the whole period, and these findings may be explained by better ascertainment of patients at the end of the period.
Abstract: The aim of the study was to obtain incidence figures for Down's syndrome throughout a period where a considerable change in the age distribution of child-bearing mothers has taken place and to study if the expected fall in incidence has occurred. In parts of the Copenhagen Metropolitan area 235 liveborn patients with Down's syndrome were ascertained in the period 1960 to 1971 in a population of 1-2 million with a total of 204771 births. All patients available were examined cytogenetically (75%). In 160 (90-4%) a regular trisomy 21 was observed. In 6-2% of the cases translocations and in 2-3% of the cases mosaics were found. Two double trisomies and a double trisomy mosaic were observed. Throughout the period 1960-71 the percentage of women over 30 years delivering children decreased from 23-4% in the beginning of the period to 16-2% at the end of the period. In the first part of the period 52-6% of the cases were born to mothers over 30, at the end of the period 40% of Down's syndrome mothers were of that age. However, the incidence was unchanged throughout the whole period, about 1-15 per 1000 births. For some age groups a steady rise in incidence of trisomy 21 cases was found throughout the whole period. These findings may be explained by better ascertainment of patients at the end of the period; however, environmental factors may also play a role.

Journal ArticleDOI
TL;DR: A role of human leukocytes in the catabolism of histamine and therefore in the modulation of Histamine-mediated inflammatory reactions is suggested.
Abstract: Histaminase (EC 1.4.3.6) activity has been demonstrated in human eosinophils and neutrophils, but not in mononuclear cells, with the use of a new and specific thin-layer radiochromatographic enzyme assay. Leukocyte histaminase was physicochemically and functionally similar to histaminase isolated from human placenta and was principally localized to the 27,000-g granule-rich fraction of eosinophil and neutrophil homogenates. Histamine methyl transferase (EC 2.1.1.8), on the other hand, was detected in monocytes but not in granulocytes, eosinophils, lymphocytes, or platelets, and was localized solely to the 100,000-g cell sap supernatant fraction. These data suggest a role of human leukocytes in the catabolism of histamine and therefore in the modulation of histamine-mediated inflammatory reactions.

Journal ArticleDOI
TL;DR: Three newborn infants with congestive heart failure had hemodynamic, angiographic, and echocardiographic features of hypertrophic subaortic stenosis (hypertrophic obstructive cardiomyopathy) and resolution of the condition during the first six months of life was shown.

Patent
12 Mar 1976
TL;DR: In this paper, a micro-method for measurement of sterols such as cholesterol, and other macromolecular substances, was disclosed utilizing enzymes for the conversion of such substances to produce ultimately hydrogen peroxide and measurement of the generated hydrogenperoxide with a membrane covered polarographic anode.
Abstract: A micro-method for measurement of sterols such as cholesterol, and other macromolecular substances, is disclosed utilizing enzymes for the conversion of such substances to produce ultimately hydrogen peroxide and measurement of the generated hydrogen peroxide with a membrane covered polarographic anode. The polarographic anode is set at a voltage so as to produce current proportional to hydrogen peroxide concentration. According to the method of this invention, the macromolecular substance under analysis enters into an enzymatic reaction in a sample chamber on the side of the membrane opposite the anode and the membrane is impermeable to such substances, but senses hydrogen peroxide. The method is adapted to measure free and total blood cholesterol in a precise, rapid, sensitive and specific manner. Other substances of a macromolecular or conventional membrane impermeable nature such as high molecular weight starches or proteins, which undergo enzymatic reaction to produce ultimately hydrogen peroxide, may be analyzed by employing this polarographic technique.