EMS regulations at a crossroad.
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California↗
Biomedical subjects
B Smith
Publications and source records attributed to B Smith.
A cell hybrid and recombinant DNA library that facilitate identification of polymorphic loci in the vicinity of the Huntington disease gene.
Somatic cell hybrids were selected that retain a derivative chromosome 5 from an individual in which the p15.1-pter segment of chromosome 5 is replaced with the p15.1-pter segment of chromosome 4. Hybrids that retain this derivative chromosome exclusively were found to be positive for G8, a DNA marker closely linked to the Huntington disease gene on chromosome 4p. From one such hybrid, a segregant was isolated that had deleted the entire q arm of the derivative chromosome but retained the p arm intact as its only detectable human DNA. A complete recombinant DNA library was prepared from this cell line, and the inserts in approximately 1/3 of the recombinant phage with human DNA were shown to be derived from 4pter-4p15.1, which represents only approximately 1% of the total human genome. The cell hybrid and DNA library represent a rapid and efficient means to identify and isolate many polymorphic DNA markers close to and flanking the Huntington disease gene.
Animals↗
Nurse training in the UK.
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Education, Nursing, Diploma Programs↗
Invasion of the mouse eye by Onchocerca microfilariae.
Onchocerca cervicalis microfilariae (mf) were injected s.c. into the scalp between the eyes of CBA/H mice. Invasion was followed by slit-lamp biomicroscopy and H & E stained serial sections at varying times post infection. The first mf observed were found 24 hr p.i. on the corneal surface in tear fluid. At 48 hr mf were observed actively swimming in the anterior chamber and by 3 d in the corneal stroma. Histologically mf appeared in orbital muscle connective tissue, subcutaneously in the eyebrows at the eyelid/conjunctiva junction from 6 hr p.i. By 12 hr some mf had moved into the suprascleral muscle junctions, the sclera and into the superior corneal stroma. By 24 hr mf were present in larger numbers in all these sites. Mf were found in all eyes up to 42 d p.i. No mf were seen in any sections of the retina or optic nerve. Rabbit antiserum raised to mf, used in an avidin-biotin immunostain to check whether mf might have been hidden within the retinal nuclear layers, revealed no mf although they were plainly seen in other ocular tissues. Retinal invasion was induced by injection of mf into the lateral tail vein: serial sections revealed mf associated with blood vessels in the sclera, suprascleral muscle blocks and inner plexiform layer of the retina from 5 min p.i.
Animals↗
Early diagnosis of the older cardiac patient with multiple disorders.
In the critically ill elderly patient, multiple organ system involvement is common. The presence of acute--or acute on chronic--cardiac, pulmonary, and renal disease in the same patient makes clinical evaluation for heart failure or volume depletion notoriously difficult. When the clinician is faced with a bewildering array of hemodynamic possibilities in a critically ill patient, the Swan-Ganz catheter may allow a baseline definition of the patient's volume status and cardiac output, on which further therapy and prognosis can be based.
Aged↗
Human Cu/Zn superoxide dismutase cDNA: isolation of clones synthesising high levels of active or inactive enzyme from an expression library.
The molecular cloning and nucleotide sequence of the cDNA for human Cu/Zn superoxide dismutase (SOD) is reported. The tacI promoter has been used to direct the synthesis in E. coli of this SOD which is soluble, stable, and of normal specific activity. The N-terminal methionine is removed from this protein. A construction with a ribosome binding site identical to that of the lacz gene 5' of the initiator methionine codon, resulted in low levels of SOD. An in vitro mutagenesis procedure was used to randomize the four nucleotides preceding the initiator methionine codon and the silent third positions of the codons specifying the second and third amino acids. Analysis of a sample of 500 clones showed that ca. 25 clones synthesised 5% or more of soluble cell protein as SOD. The nucleotide sequences of high level expressors showed a predominance of A and T residues in the variable positions 5' of the initiator methionine codon. An SOD mutant (ala4----gln) was discovered during the sequencing and shown to lack dismutation activity. Secondary structure predictions for the 5' regions of the mRNAs from high and low level expressors support the hypothesis that initiation of translation is much reduced if part of the region complementary to 16s rRNA is base paired in a stem structure.
Base Sequence↗
MOPP regimen as primary chemotherapy for brain tumors in infants.
Seventeen infants with central nervous system malignancies, all with tissue diagnosis, were treated with the combination chemotherapy nitrogen mustard, vincristine, procarbazine and a steroid (MOPP) as primary therapy following surgery. Diagnoses include: 7 astrocytomas (grade: 3-I, 3-II, 1-III), 6 medulloblastomas, 2 ependymoma/astrocytoma mixed, 1 ependymoma and 1 primitive neuroectodermal tumor. Fourteen were under 2 years of age, 2 between 2 and 3 years of age, and 1 between 3 and 4 years of age. Fifteen responded and 2 failed. Of the responders, 6 are in continuous complete remission (median duration 28.9+ months) and 9 are in relapse (median duration of remission 10.3 months). Of the 2 patients who failed and 9 who relapsed, 4 expired and 6 are living in partial or complete remission. We conclude that MOPP therapy is well tolerated, has effectiveness, and allows postponement of potentially debilitating radiotherapy in infants with brain tumors.
Antineoplastic Combined Chemotherapy Protocols↗
Fragile sites and structural rearrangements in cancer.
We retracted information from a computerized databank which contains the cytogenetic findings of 17,000 patients with leukemia and lymphoma. Cytogenetic data from patients with solid tumors were compiled from Dr. Mitelman's catalogue on "Chromosome aberrations in cancer". We compared the observed distribution of breaks in chromosome bands involved in structural rearrangements with the random distribution of breaks generated by Monte Carlo simulation and showed that a majority but not all of the bands known to contain a fragile site are involved in structural aberrations in cancer and that some of them are associated with specific chromosome structural changes in specific types of cancer.
Chromosome Aberrations↗
Bone and joint infections caused by gram-positive bacteria: treatment with cefotaxime.
Cefotaxime treatment was evaluated in 41 patients with serious bone and joint infections. Septic arthritis and bursitis (8), acute and chronic osteomyelitis (33) were treated with 3 to 12 g of cefotaxime per day for three to 52 days. The diagnosis of osteomyelitis or septic arthritis was made on the basis of clinical and roentgenographic evidence of infection. The diagnosis of a joint infection was confirmed by a positive culture of a joint aspirate sample. The diagnosis of a bone infection was confirmed by either a positive culture of a bone biopsy or of blood in combination with a positive bone scan or roentgenogram. Staphylococcus aureus was the most frequently isolated pathogen. Overall, 36 of 41 patients, who met all criteria for evaluation, had satisfactory responses to cefotaxime. The drug was well tolerated by all patients. However, six patients had a direct Coomb's test, two patients were noted to be neutropenic and two patients developed a macular rash. It is concluded that cefotaxime is a useful and safe antibiotic for the treatment of osteomyelitis and septic arthritis.
Adolescent↗
Pulmonary strongyloidiasis. Diagnosis by sputum gram stain.
Sputum Gram stain was diagnostic for pulmonary strongyloidiasis in four patients from Tennessee with chronic obstructive lung disease treated with steroids. The case reports of these patients and photomicrographs of the larval forms by Gram stain are presented. Sputum Gram stain may be a useful procedure to screen for pulmonary strongyloidiasis in steroid-treated patients with chronic lung disease who come from an endemic area.
Aged↗
Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium.
The infiltration of neutrophils into ischemic myocardium exacerbates myocardial damage upon reperfusion, whereas drugs that inhibit neutrophil activity or function reduce infarct size. Consequently, it is important to accurately assess the myocardial neutrophil content. Histologic sections and radiolabeled cells have been used, but have major limitations. We have developed a method to measure the neutrophils present in cardiac tissue by utilizing a spectrophotometric assay for the neutrophil-specific myeloperoxidase enzyme (MPO) (Bradley et al., 1982a). Coronary artery occlusion and reperfusion in the anesthetized dog induces neutrophil accumulation into the ischemic heart, which shows a linear relationship with time. An increase in activity from 0.014 +/- 0.001 units (u) MPO/100 mg tissue to 0.091 +/- 0.02 u MPO/100 mg is already apparent at the end of the 90-min occlusion period. This activity increases over 5 hr reperfusion to 0.32 +/- 0.018 u MPO/100 mg tissue. Histologic analyses confirmed the temporal association of neutrophil accumulation. Moreover, there is a correlation between infarct size and tissue MPO activity. Measuring the MPO content in preparations of canine neutrophils, which is directly correlated with cell number, allows units of MPO activity to be converted into a tissue neutrophil content. This assay is simple, sensitive, and provides a quantitative index of myocardial neutrophil accumulation that can be used to study the relationship between leukocyte infiltration and myocardial injury.
Animals↗
Hypergammaglobulinemia in histiocytosis X.
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Adolescent↗
Temporalis muscle transfer: a vascular bed for autogenous dermis-fat orbital implantation.
Nine patients with contracted avascular sockets who were unable to wear prostheses, and whose prospects for maintaining viable autogenous dermis-fat grafts were diminished, underwent temporalis muscle transfer into the orbit through a window in the lateral orbital wall. The temporalis transposition was used as a vascular bed for dermis-fat orbital implantation. Postoperatively, seven of nine patients were able to wear satisfactory prostheses and four of nine patients had amelioration of their superior sulcus deformities.
Adipose Tissue↗
Reflections in ophthalmic plastic surgery.
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History, 20th Century↗
Double composite lid reconstruction: a new method of upper and lower lid reconstruction.
The double composite grafting technique utilizes two composite lid grafts from an opposing upper and lower lid for reconstruction of extensive lid defects. These two composite grafts are covered by a rotational pedicle advancement skin flap. The skin defect created by such an advancement graft is covered by a free skin graft. The donor areas are closed directly by a layer-by-layer approximation. This new single-stage technique allows reconstruction of large lid defects without covering an affected eye for a prolonged period and without jeopardizing the irreplaceable entity of a "normal" lid margin.
Eyelids↗
Depletion and repopulation of epidermal dendritic cells after allogeneic bone marrow transplantation in humans.
We have observed marked depletion of epidermal dendritic cells, defined by monoclonal antibodies directed against HLA-DR (Ia-like) and T6 antigens, after allogeneic bone marrow transplantation. To more precisely characterize this observation, we examined a total of 39 sequential biopsies from 15 patients both before and after allogeneic bone marrow transplantation. Profound depletion of HLA-DR and T6-positive epidermal dendritic cells was observed early after transplantation (1-4 weeks), followed by gradual and variable repopulation. Transmission electron microscopy confirmed absence of dendritic cells in selected biopsies. Depletion of dendritic cells did not appear to be related to development of clinical or histologic evidence of graft-versus-host disease, suggesting that depletion may relate to pretransplant conditioning regimens. The rate of return of these cells, however, may be influenced by the presence or persistence of clinical disease. Repopulation of epidermal dendritic cells after initial depletion in bone marrow transplantation represents a human model relevant to studies concerned with the origin and kinetics of Langerhans cells.
Adolescent↗
Interferon enhancement of HLA-DR antigen expression on epidermal Langerhans cells.
Langerhans cells (LCs) are dendritic epidermal cells whose ability to function as accessory/stimulatory cells in initiating the immune response is, like that of macrophages, dependent on the expression of class II major histocompatibility antigens. In normal human skin approximately 50% of LCs identified by cell surface T6 antigenicity also express HLA-DR histocompability determinants. We report here that recombinant DNA-derived human interferon (IFN)-gamma, but not IFN-alpha 2, induces the expression of HLA-DR antigens by the population of human epidermal LCs on which such antigens normally are not detected. IFN-gamma effectively induced HLA-DR on both neonatal and adult epidermal LCs and such induction was blocked by neutralization with a murine monoclonal antibody to IFN-gamma. IFN-gamma induction of LC HLA-DR expression is inhibited by prostaglandin E2 (PGE2) and is mimicked by the presence of fatty acid cyclooxygenase inhibitors, known to reduce PGE2 production. These results suggest that IFN-gamma may play a role in regulating skin-associated immune responses through enhanced expression of HLA-DR antigens on LCs and that such enhancement may be mediated by alterations in arachidonic acid metabolism.
Cyclooxygenase Inhibitors↗
Mechanical aspects of chest wall distortion.
During passive inflation of the respiratory system, the rib cage (RC) expands because the pressure applied to it [approximately equal to abdominal pressure (Pab)] increases. Similar Pab-tidal volume (VT) relationships between passive and spontaneous inspirations would occur only if 1) Pab acts on RC equally in the two situations (no distortion) or 2) the extradiaphragmatic inspiratory muscles expand RC, compensating for distortion. In anesthetized adult rats and in sleeping human infants the passive relationships between VT and Pab or abdomen motion (AB) were constructed by occluding the airways during expiration. For a given Pab (or AB) in active breathing VT averaged 55% (rats) and 49% (infants) of the passive volume change. With phrenic stimulation in rats VT was only slightly less than during spontaneous breathing, indicating that, in the latter case, the respiratory system was essentially driven only by the diaphragm. In both species occasional breaths with large RC expansion occurred, and VT was then equal to or larger than the passive volume at iso-Pab. We conclude that 1) RC distortion decreases VT to approximately half of the passive value and 2) being on the relaxation curve reflects "compensated" distortion and not absence of it.
Abdomen↗