Showing papers by "Boston Children's Hospital published in 1979"

α -Globin gene organisation in blacks precludes the severe form of α -thalassaemia

Abstract: IN most human populations, the α-globin structural gene loci are duplicated so that each diploid cell contains four copies of α-globin genes1–3. In α-thalassaemia, a hereditary disorder of α-globin chain synthesis, the most common molecular lesion is due to the deletion of the α-globin genes4–7. In the Asian population, four main α-thalassaemia syndromes of increasing clinical severity are recognised: (1) the silent carrier state (α-thalassaemia-2) with no clinical manifestation; (2) α-thalassaemia trait (α-thalassaemia-1), characterised by microcytic red blood cells but little or no anaemia; (3) haemoglobin-H disease, which manifests as haemolytic anaemia; and (4) homozygous α-thalassaemia, in which the afflicted fetus dies at or around term from hydrops fetalis. These four syndromes are due to the deletion of from one to all four copies of the α-globin genes. In this study, we have characterised α-thalassaemia in people of African origin. Haemoglobin screening programmes have shown that α-thalassaemia occurs in the black population8–10. Recently we have demonstrated by complementary DNA–DNA hybridisation that in black individuals with clinically well defined α-thalassaemia trait, two of the four normal α-globin genes were deleted11. However, in this population, haemoglobin-H disease is rare and homozygous α-thalassaemia has never been found12,13. For this study we have used the restriction endonuclease mapping technique of Southern14 to delineate the nature of the deletion of the α-globin genes.

Senescent Human Diploid Cells in Culture: Survival, DNA Synthesis and Morphology

Abstract: Senescent human diploid cell cultures (WI-38 and WI-26) were studied during Phase III for survival time, ability to synthesize DNA, and nuclear morphology. Periodic transfers made during a 6-month period of Phase III showed that cultures were maintained with only slight variations in cell number. No sign of spontaneous acquisition of infinite proliferative potential was observed. The increase in the number of multinucleated cells found during the period of observation showed that progressive changes occur in Phase III. A certain proportion of cells maintained the ability to incorporate tritiated thymidine throughout the period of observation.

Multiple Isolates of Pseudomonas aeruginosa with Differing Antimicrobial Susceptibility Patterns from Patients with Cystic Fibrosis

Abstract: Clinical isolates of Pseudomonas aeruginosa from patients with cystic fibrosis were studied in an effort to determine the unique characteristics of the infecting strains and to elucidate the pattern of colonization. Of 413 patients studied, 81% were chronically infected with P. aeruginosa. Patients from whom P. aeruginosa was never or only occasionally isolated were in better clinical condition than the chronically infected patients. Isolates were classified into six morphologic varieties: classic, rough, mucoid, gelatinous, dwarf, and enterobacter. Most patients had two or more of these varieties. Such multiple varieties from the same individual were of the same serotype but often differed in antibiotic susceptibility as determined by both the disk and the minimal inhibitory concentration methods. These differences were apparent when mucoid strains were compared with nonmucoid strains and when nonmucoid strains were compared with one another. Studies of antibiotic susceptibility should be performed on each morphologically different type of P. aeruginosa obtained from patients with cystic fibrosis. Chronic pulmonary infection is responsible for most of the morbidity and almost all of the mortality in patients with cystic fibrosis. Severe chron

The trachea in children with tracheo-oesophageal fistula.

Abstract: Forty tracheas from children with tracheo-oesophageal fistulae were histologically analysed for structural deformity. Thirty (75%) had a deficiency of cartilage; 24 (60%) showed an increase in the length of the transverse muscle, and 26 (65%) had a longer than average internal perimeter. Only six tracheas were entirely normal. The position of the fistula bore little relationship to the abnormalities found. Since in only nine patients were abnormalities restricted to the site of the fistula, we believe that careful examination of the whole length of the trachea is needed at the time of surgery to determine the extent of the anomaly and to anticipate tracheal problems. This is also relevant to autopsy studies and to elucidate the cause of death.

Comparative epidemiology of two rotavirus serotypes and other viral agents associated with pediatric gastroenteritis

Abstract: Human rotavirus (HRV) type 1 or 2, adenovirus, or non-cultivatable 27 nm virus-like particles were demonstrated by electron microscopy and/or rotavirus ELISA in fecal samples from 45.5% of 604 gastroenteritis inpatients, 25.0% of 200 gastroenteritis outpatients and 6.0% of 812 control subjects, all sampled at Children's Hospital National Medical Center. Washington, DC. Rotaviruses were the most common pathogens detected as 39% and 22% of gastroenteritis inpatients and outpatients, respectively, shed HRV. About three-fourths of the rotaviruses were type 2, which was prevalent during five successive epidemic years from January, 1974, through June, 1978. HRV type 1 was detected in the last four successive epidemic years and represented nearly half of the HRV infections observed among gastroenteritis inpatients during the year 1977--1978. Both rotavirus serotypes were detected most often in the month of January, when 71% of 123 gastroenteritis inpatients and 62% of 34 gastroenteritis outpatients shed one of these viruses. Uncultivatable adenoviruses were detected significantly more frequently in stools from patients with gastroenteritis (3.9%) than from control subjects (0.6%), suggesting that these viruses played a role in acute enteric disease. The frequency of detection of 27 nm particles was not significantly different in gastroenteritis and control patients. Numerically, HRV infection was detected most often in gastroenteritis inpatients who were 10 through 12 months of age. The group of gastroenteritis inpatients with the highest percentage of HRV infection was 13 through 15 months of age. The excess of type 2 HRV infection relative to type 1 infection was especially large in those aged 7 through 24 months. Lower socioeconomic status or greater crowding appeared to be associated with the occurrence of rotavirus infection earlier in life and earlier in the epidemic year.

Exercise-Induced Hypertension After Surgical Repair of Coarctation of the Aorta

Abstract: To study exercise-induced hypertension after surgical repair of coarctation of the aorta, 30 patients aged 6 to 30 years (median 14) were exercised to exhaustion on a treadmill using the Bruce protocol. Twenty patients with hemodynamically insignificant heart disease served as controls. Systolic blood pressure was measured simultaneously in the arm and leg before and immediately after exercise. There was no significant difference between the control and coarctectomy groups with regard to age at exercise, duration of exercise, maximal heart rate or serum lactate after exercise. Blood pressure in the arm increased significantly after exercise in both groups (control group: 110 [range 90 to 140] to 135 [range 114 to 164] mm Hg, P P P P P r = 0.91, P This high correlation suggests that the residual obstruction across the site of the coarctectomy causes the observed postexercise systolic hypertension in the arm. Exercise testing with blood pressure measurements should be performed in all children after repair of coarctation of the aorta. In those whose postexercise systolic pressure in the arm exceeds 200 mm Hg, catheterization should be considered to measure central aortic pressure with exercise because reoperation, antihypertensive medication or restriction of severe physical effort may be necessary.

Periodic Transfusions for Sickle Cell Anemia and CNS Infarction

Abstract: Recurrences of CNS infarction often lead to progressive neurologic disability in sickle cell anemia. To prevent such reccurrence, a periodic blood transfusion program was begun in 1969. Currently, 27 patients are on this regimen. Before inclusion in the program, 12 patients had had one to nine CNS recurrences each. Since the program was started, two patients have had transient CNS ischemia. There were no other recurrences and none of the patients have shown progression of neurologic abnormalities. In addition, there was a striking decrease in bacterial infection and pain. We conclude that periodic transfusions are effective in preventing recurrent CNS infarction in sickle cell anemia. The benefits must be weighed against the potentially serious problem of iron overload, as evidenced by moderately elevated serum ferritin values.

Stimulation of the pituitary-adrenocortical axis by nerve growth factor.

Abstract: Nerve growth factor (NGF) is a protein essential for the development and maintenance of the peripheral sympathetic nervous system, causing responsive neurones to increase in size and to extend neurites. Biochemically, the selective induction of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase key enzymes in catecholamine biosynthesis is one of its most characteristic effects. Both the morphological and biochemical effects are modulated by glucocorticoids, suggesting a close relationship between specific effects of NGF and hormone action. NGF has been shown to induce an increase in adrenal cyclic AMP in intact but not in hypophysectomised rats, and so we have looked directly at the effect of systemic administration of NGF on the hypothalamo-pituitary-adrenal axis. We report here that NGF induced an enhanced secretion of adrenocorticotropin (ACTH) and a prolonged increase in plasma glucocorticoid concentration after intravenous (i.v.) injection. Such effects could have important implications for the biological activity of NGF.

Effect of particle size on lead absorption from the gut.

Abstract: The relationship between particle size and absorption of lead particles from the gastrointestinal tract of the rat has been investigated. Preparations of metallic lead of particle size between 0 and 250μ were incorporated in laboratory rat diets and absorption determined by measurement of tissue lead concentrations attained under standard conditions. An inverse relationship was found between particle size and lead absorption; this relationship was most marked in the 0 to 1001μ range. A five-fold enhancement of absorption was observed from the diet with lead particles of mean size 6μ, compared with 197μ particle size. Lead absorption from dried paint films containing lead chromate and lead octoate was measured using a similar technique. A marked enhancement of absorption was observed for both paints when particle size was reduced from 500 to 1,000 μ to < 50μ.

Compression of the ECG by Prediction or Interpolation and Entropy Encoding

Abstract: Compression of digital electrocardiogram (ECG) signals is desirable for two reasons: economic use of storage space for data bases and reduction of the data transmission rate for compatibility with telephone lines. In a sample of 220 Frank4ead ECG's the removal of signal redundancy by second-order prediction or interpolation with subsequent entropy encoding of the respective residual errors was investigated. At the sampling rate of 200 Hz, interpolation provided a 6 dB smaller residual error variance than prediction. A near-optimal value for the interpolation coefficients is 0.5, permitting simple implementation of the algorithm and requiring a word length for arithmetic processing of only 2 bits in extent of the signal precision. For linear prediction, the effects of occasional transmission errors decay exponentially, whereas for interpolation they do not, necessitating error control in certain applications. Encoding of the interpolation errors by a Huffman code truncated to ±5 quantization levels of 30 ?V, required an average word length of 2.21 bits/sample (upper 96 percentile 3 bits/sample), resulting in data transmission rates of 1327 bits/s (1800 bits/s) for three simultaneous leads sampled at the rate of 200 Hz. Thus, compared with the original signal of 8 bit samples at 500 Hz, the average compression is 9:1. Encoding of the prediction errors required an average wordlength of 2.67 bits/sample with a 96 percentile of 5.5 bits/sample, making this method less suitable for synchronous transmission.

X-Linked mental retardation with macro-orchidism and the fragile site at Xq27 or 28

Abstract: Data are presented suggesting that the form of X-linked mental retardation with macro-orchidism and the form associated with a fragile site at Xq27 or 28 are the same entity.

Cow's milk allergy, incidence and pathogenetic role of early exposure to cow's milk formula.

Abstract: A study was performed in infants under the age of 12 months born during 1974 and admitted to St. Goran's Children's Hospital with symptoms suggestive of cow's milk allergy (CMA). The aims of the study were to determine the role of early exposure to cow's milk formulas as a predisposing factor to CMA and to estimate the incidence of CMA in infancy. Twenty-five infants fulfilled the criteria for CMA. Available records were reviewed and a careful history was obtained from the mothers on two occasions. The patient group was compared with a control group. Sixteen of the 25 infants were exposed to cow's milk protein during their first week in the nursery for newborns, 6 were exposed before the end of the fourth week of life, and 3 infants were apparently not exposed. All infants were breast fed 3 to 26 weeks before re-exposure and occurrence of symptoms. Infants with CMA were given cow's milk formulas during their first 4 weeks of life significantly more often than infants in the control group (p less than 0.01). The incidence of CMA was approximately 1 : 200. The first 4 weeks after birth seem to be a particularly vulnerable period. Hence, in order to prevent CMA, infant formula should not be given--even occasionally--during this period.

The interaction of stressors in the induction of increased levels of fluctuating asymmetry in the laboratory rat

Abstract: Recent studies on fluctuating dental asymmetry have isolated single stressors as causative agents. Since most stressors are composite in nature, the present study was designed to determine the effects of the interaction of stressors in the induction of fluctuating dental asymmetry. Pregnant rats were assigned to one of six treatment groups and stressed with various combinations of heat, cold, noise and protein deprivation. The levels of fluctuating dental asymmetry were assessed and it was found that all protocols produced higher levels of asymmetry than found for control animals. Noise and reduced protein exhibited an additive effect and the interaction of stressors produced a reduction in litter size. Suggestions were offered for further research in this expanding field.

The tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate enhances the proliferative response of balb/c-3t3 cells to hormonal growth factors.

Abstract: Stimulation of Balb/c-3T3 cell growth by TPA requires factors found in serum We examined the interaction between TPA and serum growth factors in the stimulation of cell growth The number of cells synthesizing DNA (incorporating 3H-thymidine) within 24 to 30 hours after the addition of TPA and the growth factors to density-inhibited Balb/c-3T3 cultures in serum-free medium was determined by autoradiography With no additions or with TPA (30--300 ng/ml) alone, only 3--7% of cells synthesized DNA However, TPA synergistically promoted DNA synthesis in combination with each of the defined serum growth fractions, platelet derived growth factor and platelet poor plasma TPA also synergistically promoted DNA synthesis in combination with purified growth factors including fibroblast growth factor, insulin (10(-6)--10(-5)M), and epidermal growth factor In all conditions, TPA enhancement of DNA synthesis also resulted in an increase in cell number Because TPA synergistically enhanced the activity of each growth factor tested, it did not act identically to any of the growth factors

Fine structure of initial outgrowth of processes induced in a pheochromocytoma cell line (PC12) by nerve growth factor.

Abstract: Cells of the PC12 line (which is derived from a rat pheochromocytoma) develop neuron-like processes upon exposure to nerve growth factor (NGF), and thus provide an opportunity to study this phenomenonde novo. We have used the transmission electron microscope to analyse the early stages of process outgrowth (1, 2, 3 and 7 days) to determine what organelles are involved and in what sequence they appear during development. Despite the non-synchronous response to NGF, we can derive three main stages in early process formation. (1) NGF-treated cells develop conical extensions similar to, but larger and more numerous than those of controls. Extensions terminate in bulbous expansions that contain large number of chromaffin-like granules and bear microspikes filled with microfilaments. (2) The extensions of NGF-treated cells then acquire membranous organelles indicative of transmitter packaging and/or recycling of cytoplasmic membranes, for example, tubular reticulum, clear and dense-cored vesicles, multivesicular bodies, and lysosomes. (3) As processes elongate, they develop a shaft that contains an array of microtubules and fine tubular reticulum dispersed in a filamentous matrix, and varicosities that exhibit the same organelles seen in stage 2. The discussion stresses the similarities in the outgrowth of processes in PC12 cells and neurons, and speculates that NGF causes a change in organization and/or quantity of organelles that already exist in non-treated control cells.