Showing papers by "Boston Children's Hospital published in 1986"

Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene

Abstract: Duchenne muscular dystrophy (DMD) and the less severe Becker muscular dystrophy (BMD) are human X-linked muscle-wasting disorders that have been localized to the band Xp21 by genetic linkage analysis1–9 and cytologically detectable abnormalities10–12. A cloned DNA segment, DXS164 (or pERT87), has been shown to detect deletions in the DNA of unrelated DMD and BMD males13–15. Here we present the nucleotide sequence of two highly conserved DNA fragments from the DXS164 locus and their homologous sequences from the mouse X chromosome. One of the human conserved segments hybridized to a large transcript in RNA isolated from human fetal skeletal muscle and was used to isolate cDNA clones which cover approximately 10% of this transcript. The cDNA clones map to Xp21 and hybridize with a minimum of eight small regions that span 130 kilobases (kb) of the DXS164 locus. These expressed sequences are candidates for portions of the gene responsible for both DMD and BMD.

Infections with herpes simplex viruses (1).

Abstract: IN the 12 years since the last review of herpes simplex virus (HSV) infections in these pages,1 there have been substantial advances in our knowledge of the clinical manifestations, pathogenesis, a...

Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy

Abstract: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder for which the biochemical defect is as yet unknown. Recently, two cloned segments of human X-chromosome DNA have been described which detect structural alterations within or near the genetic locus responsible for the disorder. Both of these cloned segments were described as tightly linked to the locus and were capable of detecting deletions in the DNA of boys affected with DMD. In an attempt to determine more precisely the occurrence of these deletions within a large population of DMD patients and the accuracy of one of the segments, DXS164 (pERT87), in determining the inheritance of the DMD X chromosome, the subclones 1, 8 and 15 were made available to many investigators throughout the world. Here we describe the combined results of more than 20 research laboratories with respect to the occurrence of deletions at the DXS164 locus in DNA samples isolated from patients with DMD and Becker muscular dystrophy (BMD). The results indicate that the DXS164 locus apparently recombines with DMD 5% of the time, but is probably located between independent sites of mutation which yield DMD. The breakpoints of some deletions are delineated within the DXS164 locus, and it is evident that the deletions at the DMD locus are frequent and extremely large.

Interstitial deletion of (17)(p11.2p11.2) in nine patients

Abstract: We describe a new and distinct syndrome involving an interstitial deletion of the short arm of choromosome 17 in nine unrelated patients (six males; three females) ranging in age from 3 months to 65 years. In eight patients, a deletion of a portion of band 17p11.2 was associated with a striking similar phenotype including brachycephaly, midface hypoplasia, prognathism, hoarse voice, and speech delay with or without hearing loss, psychomotor and growth retardation, and behavior problems. The one patient with a complete deletion of band 17p11.2 was more severely affected with facial malformations, cleft palate, and major anomalies of cardiac, skeletal, and genitourinary systems; the patient died at age 6 months. Careful cytogenetic analysis including high-resolution techniques will be important for the further identification of patients with this previously unrecognized deletion syndrome.

Implantable gas-containing biosensor and method for measuring an analyte such as glucose

Abstract: The present invention relates to a novel implantable biosensor and method for sensing products, such as hydrogen peroxide, generated from an enzymatic reaction between an analyte, like glucose, and an enzyme in the presence of oxygen. The novel implantable biosensor is uniquely equipped with an enclosed chamber for containing oxygen and can be adapted for extracting oxygen from animal tissue adjacent the container. The reservoir of oxygen contained in the enclosed chamber is supplied to the enzymatic reaction from the side of the membrane opposite the enzyme. The enclosed chamber is uniquely designed to be impermeable to substances, like liquid and cells, that possibly can interfere with the supply of the oxygen permeating through the membrane to the enzymatic reaction. Also, the implantable biosensor is designed to optically or electrically sense products generated from the enzymatic reaction which serve as a function of the analyte.

Natural history of untreated idiopathic scoliosis after skeletal maturity.

Abstract: A total of 187 random cases of untreated idiopathic scoliosis, seen from a minimum of 15 to a maximum of 47 years after the end of growth, were reviewed. All curves increased after skeletal maturity (average progression: 0.4 degrees per year). Thoracic curves tend to progress more than lumbar, lumbar more than thoracolumbar, and thoracolumbar more than double major curves. Pain was present in 114 cases (61%) and appeared more frequently in women, after pregnancies, and with fatigue. Cardiopulmonary symptoms were present in 42 patients (22%), especially those with thoracic and thoracolumbar curves greater than 40 degrees. Psychologic disturbances were found in 35 cases (19%), mostly female patients with thoracic curves greater than 40 degrees. The cosmetic appearance of these patients at long-term follow-up was better compared with that at the end of growth, even though the curves progressed. Patients with decompensation of the trunk at the end of growth seemed to improve with time. In an unselected group of patients with severe curves a mortality rate of 17% was found, twice as much as in the Italian general population.

New multiple congenital anomalies/mental retardation syndrome with cardio-facio-cutaneous involvement―The CFC syndrome

Abstract: Eight patients (4 males, 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which was designated the Cardio-Facio-Cutaneous (CFC) syndrome and which includes congenital heart defects, characteristic facial appearance, ectodermal abnormalities, and growth failure. Cardiac defects were variable, the most common being pulmonic stenosis and atrial septal defect. Typical facial characteristics were high forehead with bitemporal constriction, hypoplasia of supraorbital ridges, antimongoloid slant of palpebral fissures, depressed bridge of nose, and posteriorly angulated ears with prominent helices. The hair was usually sparse and friable. Skin changes varied from patchy hyperkeratosis to a severe generalized ichthyosis-like condition. All cases were sporadic in occurrence, there was no family history of consanguinity, and chromosomes were normal. Although presumed to be genetic, the cause of the CFC syndrome remains unknown.

Structure of pre-pro-von Willebrand factor and its expression in heterologous cells

Abstract: Von Willebrand factor (vWF), a multifunctional haemostatic glycoprotein derived from endothelial cells and megakaryocytes, mediates platelet adhesion to injured subendothelium and binds coagulation factor VIII in the circulation. Native vWF is a disulphide-bonded homopolymer; the monomeric subunits, of apparent relative molecular mass (Mr) 220,000 (220K) are derived from an intracellular precursor estimated at 260–275K (refs 1–5). Multimer assembly is preceded by the formation of dimers, linked near their C-termini, which then assemble into filamentous polymers. The importance of the removal of the large vWF pro-polypeptide during multimer assembly, and whether this or other stages of the complex post-translational processing require components specific to endothelial cells or megakaryocytes, is unknown. Here we report an analysis of the complete sequence of pre-pro-vWF and expression of the molecule in heterologous cells. The vWF precursor is composed of several repeated subdomains. When expressed in COS and CHO cells, it is cleaved and assembled into biologically active high relative molecular mass disulphide bonded multimers. This suggests that the information for assembly of this complex molecule resides largely within its primary structure.

Double-blind evaluation of a lignocaine-prilocaine cream (EMLA) in children. Effect on the pain associated with venous cannulation.

Abstract: The effect of the topical application of a lignocaine-prilocaine cream (EMLA) on the pain of venous cannulation was tested in a double-blind manner Sixty boys and girls between the ages of 4 and 10 yr who were to undergo surgery participated in the study No analgesic premedic-ation was given and the venous cannulation was performed during the preparation for general anaesthesia Pain was assessed by the anaesthetist and the patient using a verbal rating scale and two different pictorial scales The effect of EMLA in the alleviation of the pain of venous cannulation was considered significantly better than placebo by both anaesthetist (P

The medical and surgical management of typhlitis in children with acute nonlymphocytic (myelogenous) leukemia

Abstract: The treatment of acute leukemia in childhood has been increasingly successful. Infectious complications are the major cause of morbidity and mortality among these patients receiving aggressive chemotherapy. In particular, neutropenic enterocolitis or typhlitis has had a reported mortality of 50% to 100%. The authors reviewed a series of 77 previously untreated patients with acute myelogenous leukemia begun on treatment from March 1976 to June 1984 to better define the characteristics of typhlitis and its optimum management. Twenty-five patients had episodes of typhlitis, characterized by fever, abdominal pain, and tenderness, occurring during periods of neutropenia. Ten of these patients had watery diarrhea as a major additional symptom, and nine patients had a significant episode of gastrointestinal bleeding. In seven instances, blood culture results were positive, all for intestinal flora. The episodes of typhlitis occurred most frequently during the induction therapy (19 patients). Five patients experienced typhlitis during maintenance therapy, and one patient had acute appendicitis. Two patients had typhlitis during their reinduction therapy, and of note, one had had abdominal symptoms during her initial induction. All patients were treated initially with broad-spectrum antibiotics and bowel rest. Four criteria have been used for surgical intervention: (1) persistent gastrointestinal bleeding after resolution of neutropenia and thrombocytopenia and correction of clotting abnormalities; (2) evidence of free intraperitoneal perforation; (3) clinical deterioration requiring support with vasopressors, or large volumes of fluid, suggesting uncontrolled sepsis; and (4) development of symptoms of an intra-abdominal process, in the absence of neutropenia, which would normally require surgery. Using these criteria, five patients required surgical intervention for typhlitis or its sequelae and one for acute appendicitis. There was one perioperative death resulting from miliary tuberculosis. Among the 21 patients managed medically, there was 1 death resulting from typhlitis in a patient in whom surgery was deferred because of her multiple failures to enter remission.

Thrombotic cerebral vasculopathy associated with herpes zoster

Abstract: We describe the clinical, radiographic, and pathological findings in 3 patients with large-vessel cerebral vasculopathy following herpes zoster. Two of the patients were studied at postmortem examination, and a brain biopsy was performed in the third. Each of the 3 patients suffered thrombotic occlusions of large vessels without notable inflammatory or granulomatous changes following trigeminal or segmental herpes zoster infection. In the 2 autopsied patients, varicella-zoster virus (VZV) antigens were detected by immunoperoxidase staining within the media of the affected cerebral arteries. Little or no inflammation was associated with the foci of the VZV antigens. These studies provide evidence that the vasculopathy following herpes zoster may result from direct VZV infection of the artery and the in situ thrombosis can develop within the infected vessels in the absence of clear inflammatory vasculitis.

Characterization of the two nonallelic genes encoding mouse preproinsulin.

Abstract: We have cloned and sequenced the two mouse preproinsulin genes. The deduced amino acid sequences of the mature mouse insulins are identical to the published protein sequences. However, the nucleotide sequence indicates that the mouse I C-peptide has a deletion of two amino acids compared with the mouse II C-peptide. We used an S1 nuclease assay to confirm the presence of the deletion and to measure the ratio of transcripts from gene I to transcripts from gene II. The mouse preproinsulin I gene, like the rat gene I, is missing the second intervening sequence that normally interrupts the C-peptide region in other insulin genes. Comparison of the 5' flanking sequences of the mouse and rat genes II indicates that they are homologous for at least 1000 base pairs. The preproinsulin I genes also share homology in their 5' flanking DNAs; however, their homology to the preproinsulin II genes extends for only about 500 base pairs.

Nucleotide sequence of pre-pro-von Willebrand factor cDNA.

Abstract: This cDNA sequence is complete except for approximately 150 bp of 5' untranslated and lOObp of 3 untranslated sequence. The whole sequence was derived on both strands. An upstream stop codon in the major open reading frame is shown by asterisks. Potential sites for N-linked glycosylation are underlined. The sites of cleavage of signal peptide and vWF pro-polypeptide (1) are indicated by arrows. The sequence ArgGlyAspSer (2) is boxed. Araino-acids are numbered to the right, relative to the initiator methionine as 1. The clones analysed were isolated from a human umbilical vein endothelial cell cDNA library (3). The repeated elements within this sequence will be discussed elsewhere (4).

Postural and lateral asymmetries in the ontogeny of handedness during infancy

Abstract: Ten newborn infants who preferred to lie with their heads turned rightward and ten who preferred to lie with their heads turned leftward had their hand-use preferences for reaching assessed at 8 different ages during the period 12-74 weeks postpartum. Eighteen infants maintained stable hand-use preferences throughout this period and the direction of their neonatal head orientation preference predicted the hand they preferred to use. The neonatal head-turn preference was maintained through the first 2 months and induced lateral asymmetries in visual regard and motor control of the hands. These lateral asymmetries are plausible contributors to mechanisms linking neonatal headturn preference to infant hand-use preference. Thus, the dextral bias in handedness may be derived, in part, from the rightward bias in neonatal head-turn preference.

Differential expression of keratin 19 in normal human epithelial tissues revealed by monospecific monoclonal antibodies.

Abstract: Three monospecific monoclonal antibodies (BA16, BA17 and A53—B/A2) recognizing different epitopes of the human keratin 19 were used to determine tissue distribution of this 40 kDa keratin polypeptide. Immunohistochemical methods revealed four different staining patterns among normal human epithelial tissues: firstly, complete negativity of the epidermis, sebaceous glands, hepatocytes and other tissues; secondly, homogeneous positivity as seen for example in the gall bladder and urinary bladder epithelium, endometrium and many other epithelia; thirdly, a mosaic of positive and negative cells among mammary gland luminal cells, prostate epithelia and some other epithelia and fourthly, a more complex heterogeneous pattern found in non-keratinizing squamous epithelia and hair follicles with generally the basal layer being the most strongly or sometimes exclusively stained. The pattern seen in non-keratinizing squamous epithelia varied considerably according to the fixation method and the antibody used as well as among different donors and in different areas of the same organ. The other three staining patterns were on the other hand nearly identical with all three antibodies on both frozen sections and sections of methacarn-fixed paraffinembedded tissues. Our results provide evidence for differential expression of the human keratin 19 at the single cell level, an observation which could be exploited in the study of epithelial differentiation and pathology.

Sexual Abuse of Boys

Abstract: To determine factors in the sexual abuse of boys, we reviewed medical records of 140 boys who were seen for evaluation at the Children's Hospital and Health Center in San Diego from 1979 to March 1984. Many of the boys were seen by one of the authors. Boys represented 9% of the 1,748 sexual abuse victims. The incidence in males increased from 7% in 1979 to 1980 to 11% in 1983. The boys were from 1 to 17 years of age. The majority of boys gave a clear, consistent, and credible history of sexual abuse. Eighty-five percent of the boys were abused by a relative or acquaintance. Physical evidence of sexual abuse was present in 95 (68%) of the victims. This paper emphasizes that boys, too, are at considerable risk for sexual abuse and that subtle physical findings of molestation are common when the child is examined by a trained, experienced physician.

Fibular a/hypoplasia: review and documentation of the fibular developmental field

Abstract: Fibular aplasia and/or hypoplasia is documented as a developmental field defect and the extent of the fibular developmental field is delineated. The term fibular a/hypoplasia denotes the clinical spectrum of fibular deficiency in different patients and also implies that aplasia can be present in one limb and hypoplasia in the other. Causal heterogeneity of fibular a/hypoplasia is demonstrated, thereby defining it as a developmental field defect. Most cases of fibular a/hypoplasia are isolated, sporadic events. An autosomal dominant form of isolated fibular a/hypoplasia with ankle joint anomaly is reviewed. Fibular a/hypoplasia may be part of more complex sporadic dysostoses; sporadic syndromes, an aneuploidy syndrome; several autosomal dominant and autosomal recessive conditions. Fibular a/hypoplasia is also postulated to occur as a result of disruption or teratogenic insult; in animals, fibular development can be disturbed by radiation, busulfan, and retinoic acid. Clinical data allow evaluation of the extent of the fibular developmental field of the lower limb. This appears to include the pubic portion of the pelvis, proximal femur (distal half being apparent tibial developmental territory), patella, anterior cruciate ligament, and lateral and/or axial foot rays (but "never" the hallux and almost never associated with polydactyly). The rare cases of fibuloulnar dimelia allow confirmation of the well known homology of mesomelic limb segments responsible for concordant ulnar and fibular (and radial and tibial) defect, if both upper and lower limbs are involved in a given condition. Because fibular a/hypoplasia is the commonest of the mesomelic paraxial hemimelias, is usually nonsyndromal, and in most cases is apparently nongenetic (ie, with negligible recurrence risk), we propose that in humans, as in several other tetrapods, the fibula is undergoing regressive evolution and hence is developmentally especially labile.