Showing papers by "Boston Children's Hospital published in 1984"
TL;DR: Results of similar studies of another embryonal neoplasm, Wilms' tumour of the kidney, show that five cases were consistent with the presence on human chromosome 11 of a locus in which recessive mutational events are expressed after abnormal chromosomal segregation events during mitosis.
Abstract: Evidence that recessive cellular alleles at specific chromosomal loci are involved in tumorigenesis has been recently shown by work on tissues from patients with retinoblastoma, a neoplasm of embryonic retina whose predisposition is inherited as an autosomal dominant trait1. A comparison of germ-line and tumour genotypes at loci on human chromosome 13, defined by restriction fragment length polymorphisms, showed that loss of the chromosome bearing the wild-type allele at the Rb-1 locus occurred frequently in the development of retinoblastoma. We report here results of similar studies of another embryonal neoplasm, Wilms' tumour of the kidney. Examination of germ-line and tumour genotypes from seven patients showed that five cases were consistent with the presence on human chromosome 11 of a locus in which recessive mutational events are expressed after abnormal chromosomal segregation events during mitosis.
513 citations
TL;DR: The cytogenetic and segregation analysis of 110 pedigrees of the mar (X) syndrome indicated an inverse relationship between IQ and the mar(X) frequency in females but not in males, but in females it was restricted to those of normal intelligence, retarded females showing no significant effect.
Abstract: Summary
The results of a cytogenetic and segregation analysis of 110 pedigrees of the mar (X) syndrome are reported. The cytogenetic study indicated an inverse relationship between IQ and the mar(X) frequency in females but not in males. A small but significant effect of age on mar(X) frequency was observed in both males and females, but in females it was restricted to those of normal intelligence, retarded females showing no significant effect.
Classical segregation analysis was performed using the program segran, analyzing sexes separately. a 20% deficit of affected males was observed, the most plausible explanation for the majority of these cases being incomplete penetrance. since this was an unexpected result, the data were scrutinized for possible biases; however, correction of these had little effect on the estimate. the penetrance of mental impairment in carrier females was estimated to be 30% and of mental impairment and/or mar(x) expression to be 56%. thus 44% of carriers cannot be detected with our definition of affection. no evidence for sporadic cases among affected males was found. complex segregation analysis was performed using the sex-linked version of pointer analysing sexes together. this was done in order to test the results from classical segregation analysis, to test for family resemblance and to estimate mutation rates. it was confirmed that there was a 20% deficit of affected males, that, penetrance of mental impairment in females was approximately 30% and that there was no evidence: for sporadic: males. thus all males with the gene appear t o have received it from their carrier mothers and all mutations must occur in sperm. the mutation rate in sperm was estimated to be as high as 7·2 × 10-4, implying that over one-half of random carrier females are fresh mutants.
our results have important implications for genetic counseling as they imply that all mothers of isolated affected males are carriers, that normal brothers of affected males have a 17% chance of carrying the gene and transmitting it to all their daughters, and that normal sisters of affected males have, at most, a 30% chance of being carriers. since there are biases in the data due to the testing of particular individuals, these probabilities must be considered approximations until they are independently confirmed.
373 citations
365 citations
TL;DR: A consistent facial phenotype was observed in all seven children exposed to sodium valproate in utero in addition to other birth defects in four; Hypospadias, strabismus, and psychomotor delay were found in two males; two children had nystagmus and two had low birth weight.
Abstract: We evaluated seven children who had been exposed to sodium valproate (or valproic acid) in utero. A consistent facial phenotype was observed in all seven in addition to other birth defects in four. The facial changes consisted of epicanthal folds which continued inferiorly and laterally to form a crease or groove just under the orbit, flat nasal bridge, small upturned nose, long upper lip with a relatively shallow philtrum, a thin upper vermillion border, and downturned angles of the mouth. Hypospadias, strabismus, and psychomotor delay were found in two males; two children had nystagmus and two had low birth weight.
357 citations
TL;DR: During 1968-77, 572 consecutive children with one or more positive urine cultures who were referred by their family doctors to one paediatric surgical outpatient clinic were investigated and prospectively recorded and an abnormality requiring treatment was found.
Abstract: During 1968-77, 572 consecutive children with one or more positive urine cultures who were referred by their family doctors to one paediatric surgical outpatient clinic were investigated and prospectively recorded. An abnormality requiring treatment was found in 45%. The yield of positive findings and need for operation were greater in those referred after one infection than in those with recurrent infection. Among those under 2 years old 90% had an abnormality. One third of children with vesicoureteric reflux showed renal scarring at the time of first attendance. The results of medical and surgical treatment over five to 15 years of follow up were analysed. They emphasised the importance of culturing the urine whenever there may be urinary infection in a child and of investigating immediately those with a positive urine culture.
277 citations
TL;DR: D diagnosis of shaken baby syndrome depends on a high index of suspicion and the physical findings of a bulging fontanelle, head circumference greater than the 90th percentile, and retinal hemorrhage.
231 citations
TL;DR: Event-related brain potentials of 13-21-year-old autistic subjects and age-matched controls were elicited by auditory stimuli in a variation of orienting response paradigms and showed that the autistic group did not misperceive novel information as non-novel and were able to make simple classification decisions as accurately as normal controls.
228 citations
TL;DR: It is demonstrated that extended survival among patients with transposition can be expected after the Mustard operation, however, over time there is a decreasing prevalence of normal sinus rhythm in survivors, as well as a small risk of sudden death.
Abstract: The Mustard operation corrects the effects of congenital transposition of the great arteries by creating an intraarterial baffle to direct pulmonary venous blood to the tricuspid orifice and systemic venous blood to the mitral orifice. To identify the long-term effects of this procedure, we followed 372 patients with complete transposition of the great arteries who survived the Mustard operation for at least three months. The mean follow-up period was 4.5 years (range, 0.4 to 15.9); the mean age at operation was 2.0 years. Mean resting heart rates were consistently lower than those for age-matched normal children. Seventy-six per cent of the patients had sinus rhythm during the year of operation — a figure that decreased to 57 per cent by the end of the eighth postoperative year. Twenty-five patients died during the follow-up period, nine suddenly. Life-table analysis revealed a cumulative survival rate of 91 per cent for 11 years and 71 per cent for 15 years after the operation. No strong risk f...
219 citations
TL;DR: Plain glass and glass coated with polylysine, collagen, fibronectin, or other monoclonal antibodies supported the growth of neural processes, but were less effective than antibody to Thy-1.
Abstract: Ganglion cells were dissociated from postnatal rat retinas, identified by specific fluorescent labels, and maintained in culture on a variety of substrates. Regeneration of processes by retinal ganglion cells was enhanced when the cells were plated on glass coated with a monoclonal antibody against the Thy-1 determinant. Plain glass and glass coated with polylysine, collagen, fibronectin, or other monoclonal antibodies supported the growth of neural processes, but were less effective than antibody to Thy-1.
196 citations
TL;DR: In situ hybridization confirms that the murine T cell receptor gene is located on chromosome 6 and the human gene on chromosome 7, and localizes these genes to band B of chromosome 6 in the mouse and bands 7p13-21 in the human genome.
185 citations
TL;DR: The genetic basis of the non-beta-lactamase ampicillin resistance in these strains appears to be chromosomally mediated, and the major mechanism of resistance is altered penicillin-binding proteins; however, other mechanisms, including permeability, may also play a role.
Abstract: Ampicillin resistance in Haemophilus influenzae is most often due to the plasmid-mediated production of TEM beta-lactamase. We studied four strains with high-level ampicillin resistance (MIC of 32 micrograms/ml with an inoculum of 10(5) CFU on solid media) which did not produce detectable beta-lactamase activity with two different detection methods. Two of the four strains contained extrachromosomal DNA by agarose gel electrophoresis. Conjugation failed to transfer ampicillin resistance; in contrast, transformation yielded ampicillin-resistant transformants in three of the four strains. These transformants did not contain detectable extrachromosomal DNA. In addition, mobilization of the resistance determinant by transformation to, or conjugation with, recombination-deficient strains was unsuccessful. DNA-DNA hybridization experiments revealed no homology of the DNA of these strains with two R plasmids (one coding for ampicillin resistance, the other for chloramphenicol and tetracycline resistance). We conclude that the genetic basis of the non-beta-lactamase ampicillin resistance in these strains appears to be chromosomally mediated. We investigated the mechanism of resistance in these strains. Enzymatic modification of penicillin was not detected by autoradiography of a thin-layer chromatogram of cell sonic extracts of three ampicillin-resistant transformant strains incubated with [14C]penicillin. To assess changes in permeability of the cell envelope, a plasmid coding for beta-lactamase was conjugated into these strains, and the hydrolysis of penicillin by intact cells and cell sonic extracts was compared. Only one of three transformant strains had significantly diminished permeability. Outer membrane proteins of these strains analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed apparent differences in comparison with the isogenic ampicillin-susceptible recipient strain. Autofluorography of a sodium dodecyl sulfate-polyacrylamide gel electrophoresis of Sarkosyl-solubilized crude membrane (the putative inner membranes) from these ampicillin-resistant transformant strains incubated with [3H]penicillin compared with the isogenic ampicillin-susceptible recipient strain revealed reduced binding to PBP 3 and 6, 3 and 4, or 4. In addition, affinity binding studies revealed decreased affinity of PBP 4 for ampicillin of all four transformants tested. We conclude that the major mechanism of resistance in these strains is altered penicillin-binding proteins; however, other mechanisms, including permeability, may also play a role.
TL;DR: Girls under 6 years of age show significantly more theta and less alpha waves compared with boys, but the developmental velocity is higher in girls than in boys and continues for a longer time; thus girls catch up with age-related changes of the boys by a later developmental spurt.
TL;DR: Six cases of meningocerebral astrocytomas attached to dura, involving the superficial cortex, in infants under 1 year of age, are reported, believed to represent a separate entity whose diagnosis cannot be accurately established without immunohistochemical techniques.
Abstract: Reported are six cases of meningocerebral astrocytomas attached to dura, involving the superficial cortex, in infants under 1 year of age. They represent 1.25% of 483 intracranial tumors in infancy studied at the Children's Hospital in the last 12 years. Five were located in the frontal lobes, with variable extension to the parietal or the parietotemporal regions, and one was located in the parietal lobe. They were all composed of a solid portion and one or more cysts, and they measured approximately 6 to 12 cm in diameter. They had spindle cells, some more plump, arranged in areas in a storiform pattern. Tumors were very rich in reticulin fibers, mimicking a mesenchymal tumor. There was very slight pleomorphism. Bizarre giant cells were not observed and lipidization was not a prominent feature. Immunoperoxidase technique was performed in all of them and showed glial fibrillary acidic protein (GFAP) in most of the tumor cells. We believe their origin is from subpial astrocytes. They probably represent a separate entity whose diagnosis cannot be accurately established without immunohistochemical techniques.
TL;DR: It is technically feasible to correct experimentally produced vesicoureteric reflux in the piglet by intravesical injection of Teflon paste--a relatively inert material.
Abstract: Vesicoureteric reflux was produced in eight piglets by opening their bladders and slitting the anterior intravesical wall of the ureter. Cystography confirmed the presence of bilateral reflux in six piglets and unilateral reflux in two. Six to eight weeks later the bladder was again opened and Teflon paste injected in the space behind the intravesical ureter, thereby creating a support for the submucosal ureter. Cystography four to six weeks after injection of Teflon paste showed absence of reflux in all animals. Intravenous pyelography showed obstruction at the vesicoureteric junction in only one of the 14 treated ureters and this was later confirmed at necropsy. Animals were followed up from one to six months and then were killed. Gross examination of the vesicoureteric region showed a well circumscribed subureteric Teflon mass of firm consistency, retaining its shape and position at the site of the injection. Histological examination showed encapsulation of the implant by a thin layer of fibrous tissue and a foreign body granulomatous reaction with histiocytes and giant cells within the implant. Hence it is technically feasible to correct experimentally produced vesicoureteric reflux in the piglet by intravesical injection of Teflon paste--a relatively inert material. It may now be possible to treat vesicoureteric reflux in man by endoscopic injection of Teflon behind the intravesical ureter.
TL;DR: Ketoconazole greatly reduced the need for analgesics; serum prostatic acid phosphatase levels fell to normal, and testosterone levels were reduced, and thirteen of fourteen evaluable patients were in remission.
TL;DR: The molecular basis for Troponin T heterogeneity was studied at the level of TnT structural gene organization and RNA expression and argues persuasively against a processive scanning model of RNA splice site selection.
TL;DR: The three main anatomic types of persistent pulmonary hypertension of the newborn are (1) maladaptation of the pulmonary vascular bed; (2) excessive muscularization of the lungs; and (3) underdevelopment of themonary vascular bed.
TL;DR: Data indicate that some colon tumors exhibit a typical pattern of enterocytic differentiation which is of foetal type and which involves at least 3 brush border membrane hydrolases.
Abstract: The expression of small intestinal hydrolases associated with the enterocyte brush border membrane was studied in human colon cancers and foetal colons, by means of monoclonal antibodies against human small intestinal sucrase-isomaltase (SI), maltase-glucoamylase (MGA), lactase (L), aminopeptidase N (APN), and dipeptidylpeptidase IV (DPP-IV). The enzymes were visualized by indirect immunofluorescence on cryostat sections of tumors developed in nude mice with 6 human colon carcinoma cell lines (HT-29, Caco-2, SW-480, HRT-18, HCT-8R, and Co-115), of 27 primary colorectal carcinomas from patients, and of human foetal (16 to 20 weeks of gestation) and normal adult small intestines and colons. All 5 monoclonals bound to the brush border of the adult small intestine, but not to that of the adult colon mucosa. Antibodies against SI, APN and DPP-IV also bound to the brush border of the foetal colons, to apical borders in HT-29 and Caco-2 tumors in nude mice, and to brush border-like structures in 7/27 tumors from patients. No binding was observed for MGA and L in either tumors or foetal colons. Binding of anti-SI antibodies to the brush border of the juxta-tumoral mucosal epithelium was observed in 9/11 samples tested. These data indicate that some colon tumors exhibit a typical pattern of enterocytic differentiation which is of foetal type and which involves at least 3 brush border membrane hydrolases. Monoclonal antibodies to small intestinal hydrolases may, therefore, be important tools for identification and characterization of some differentiated colonic tumors.
TL;DR: The results suggest that the association of specific haplotypes with specific mutations is high, but not invariant; a different β-thalassaemia mutation has arisen within each haplotype in Mediterraneans; and mutation spread from one haplotype to another occurs mainly through meiotic recombination within a 9-kilobase region 5′ to the β-globin gene cluster.
Abstract: It has been suggested that there is a close linkage between specific restriction fragment polymorphism patterns, defined as haplotypes, in the β-globin gene cluster and specific mutations in Mediterranean people with thalassaemia1. This association formed the basis of a strategy for the efficient characterization of β-thalassaemia mutations from the DNA sequence of one or two β-thalassaemia genes derived from each haplotype in each ethnic group. Subsequently, Robertson and Hill argued that this strategy greatly underestimates the number of mutations on haplotypes which are frequent among normal chromosomes2. We have therefore now analysed the proposed association and strategy quantitatively by the use of oligonucleotide hybridization and direct restriction analysis. Our results suggest that: (1) the association of specific haplotypes with specific mutations is high, but not invariant; (2) a different β-thalassaemia mutation has arisen within each haplotype in Mediterraneans; and (3) mutation spread from one haplotype to another occurs mainly through meiotic recombination within a 9-kilobase region 5′ to the β-globin gene
TL;DR: The data show that the danger of testicular infarction from an incarcerated inguinal hernia, although real, has been much over-emphasized.
TL;DR: Two classes of disease in humans that have been recently described can now be characterized as being associated with a deficiency in either 11-dehydrogenase or 11-reductase.
TL;DR: Major advances in understanding of the causes, mechanisms, and sequelae of acquired perinatal leukoencephalopathy may be made in the next decade because of improvement in brain imaging techniques, improved survival of high‐risk babies, and relatively routine follow-up of these high-risk babies.
Abstract: Between 36 and 44 weeks after conception, telencephalic white matter in the newborn appears to be particularly vulnerable to insults that result in morphological disturbances. Available evidence indicates that this disorder (or group of disorders), named acquired perinatal leukoencephalopathy, reflects a decrease in blood flow through the distal vessels supplying paraventricular white matter and/or a metabolic disturbance produced by, or in response to, an infectious agent. Major advances in our understanding of the causes, mechanisms, and sequelae of acquired perinatal leukoencephalopathy may be made in the next decade because of improvement in brain imaging techniques, improved survival of high-risk babies, and relatively routine follow-up of these high-risk babies.
TL;DR: Antenatal diagnosis by ultrasound is now often possible and was achieved in 4 cases and it is suggested that neurosurgeons should participate in such antenatal evaluations.
Abstract: A series of 74 cephaloceles (17 cranial meningoceles and 57 meningoencephaloceles) is reported. Infants born with large meningoencephaloceles containing recognizable cerebral tissue usually did badly despite endeavors to conserve brain function by expanding the cranial capacity (5 cases) or decompressing hydrocephalic ventricles (9 cases). Infants with cranial meningoceles almost all did well, even when there was associated hydrocephalus. The etiological diversity of cephaloceles is emphasized. Frontoethmoidal meningoencephaloceles, which occur with noteworthy frequency in South and Southeast Asia, require separate consideration in both genetic counseling and treatment; the associated facial deformities (hypertelorism and orbital dystopia) can be corrected with a one-stage craniofacial reconstruction. Antenatal diagnosis by ultrasound is now often possible and was achieved in 4 cases; we suggest that neurosurgeons should participate in such antenatal evaluations.
01 Jan 1984
TL;DR: X-ray and neutron diffraction results on myelin can be correlated with its chemical composition, its structure as seen by electron microscopy (EM), and its responses to nerve conduction and to physical-chemical treatments, which has led to a description of the average distribution of lipid, protein, and water in the membrane array and to the localization of specific proteins and lipids within the myelin membrane bilayer.
Abstract: The myelin sheath derives from the spiral infolding about the axon of a membrane-bound, glial cell process. The major part of the sheath consists of closely packed membrane pairs separated by narrow fluid spaces. The periodic nature of this membrane array makes myelin well suited for examination of its molecular organization by diffraction techniques. Diffraction provides a means of monitoring the separation between membranes and of analyzing the forces and interactions between them. This method, which is nonperturbing, is uniquely suited to analyzing myelin structure and stability in physiologically intact tissue, even in the living animal. X-ray and neutron diffraction results on myelin can be correlated with its chemical composition, its structure as seen by electron microscopy (EM), and its responses to nerve conduction and to physical-chemical treatments. This correlation has led to a description of the average distribution of lipid, protein, and water in the membrane array and to the localization of specific proteins and lipids within the myelin membrane bilayer. It has also led to an understanding of the role of ions in membrane-membrane interactions in myelin and the possible involvement of these ions in nerve conduction.
TL;DR: Six cases of Paget's disease of the nipple without clinical or mammographic evidence of a breast mass are described, two without underlying carcinoma of duct origin, and four with very limited duct carcinoma in situ of the most distal lactiferous ducts.
Abstract: Six cases of Paget's disease of the nipple without clinical or mammographic evidence of a breast mass are described, two without underlying carcinoma of duct origin, and four with very limited duct carcinoma in situ of the most distal lactiferous ducts. Ultrastructural and immunohistochemical studies on these cases demonstrate that Paget cells arise in situ and invalidate the prevalent "epidermotropic" theory of histogenesis. Paget's disease of the nipple is considered to be an independent in situ carcinoma and part of the general phenomenon of multicentricity in breast cancer. A therapeutic option of conservative surgical intervention and follow-up is described for five of these select patients, all of whom are presently without evidence of disease with an average follow-up of 50 months (range, 30-69 months).
TL;DR: The results clearly indicate that the concept that ACP is the initial solid mineral phase deposited in bone, and the major mineral constituent of young bone is no longer tenable, and does not provide an accurate description of the nature of the initial bone mineral deposited, or the changes that occur with maturation.
Abstract: X-ray diffraction radial distribution function analysis was used to determine if a significant amount of an amorphous solid phase of calcium phosphate exists in bone, and if so, whether the amount varies as a function of age and maturation. Unfractionated cortical bone from embryonic and posthatch chicks of various ages and a low-density fraction of embryonic bone were studied. No evidence was found for the presence of an amorphous solid phase of calcium phosphate in any of the samples studied, including the recently deposited bone mineral of the low density fraction of embryonic bone. As little as 12.5% of synthetic amorphous calcium phosphate (ACP) added to bone was readily detected by the radial distribution function technique used. The results clearly indicate that the concept that ACP is the initial solid mineral phase deposited in bone, and the major mineral constituent of young bone is no longer tenable. The concept does not provide an accurate description of the nature of the initial bone mineral deposited, or the changes that occur with maturation, nor can it acount for the compositional and X-ray diffraction changes that the mineral component undergoes during maturation and aging.
TL;DR: An elevated BTG during the first 3 weeks after onset of fever was highly associated with aneurysm formation in patients with Kawasaki syndrome, and the difference between the two groups was significant.
TL;DR: It is concluded that AN can induce lipid peroxidation in red cells in vitro and that sickle cells are more susceptible to this process than normal cells.
TL;DR: Auditory brainstem responses were evaluated in 37 children with bacterial meningitis within 48 hours of admission and suggested brainstem dysfunction at admission, and hearing losses were greatly reduced in the other two children when repeat testing was performed.
Abstract: Auditory brainstem responses were evaluated in 37 children with bacterial meningitis within 48 hours of admission. Four children (two with Haemophilus influenzae type b, and two with Streptococcus pneumoniae) had definite abnormalities of hearing detected at admission. Two of these children had severe-to-profound hearing losses which have persisted. Hearing losses were greatly reduced in the other two children (one child also was ataxic) when repeat testing was performed. Auditory brainstem responses in two additional children suggested brainstem dysfunction at admission (one child died and the other has had severe sequelae). Hearing losses occur early in the course of bacterial meningitis in some children. Further studies are required to confirm the use of auditory brainstem responses in detecting hearing losses early in high-risk children with bacterial meningitis.