Cranial trauma. Use of large bifrontal decompression in the treatment of severe head injuries in children.
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Biomedical subjects
Publications and source records attributed to A Smith.
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In a routine chromosome study it was noted that cells from a patient had different lengths of Y-chromosome: 20% of the cells had a Y-chromosome with about 40% of the normal length of heterochromatin, whereas the majority of cells had an average size Yq12 region. A break within Yq12 was found in 3-4% of the cells with the long Yq12 chromosome, indicating the presence of a possible new fragile site. The frequency of cells with the 2 different sizes of Y-chromosomes was unaffected by culture conditions, as was the frequency of cells with a break or gap. Possible consequences of a fragile-site within Yq12 are discussed.
The affect of the anti-microbial agent triclosan (alternative names Microban and Irgasan DP300) on the light emission by the bioluminescent bacterium Vibrio fischeri was determined. Triclosan at concentrations greater than 0.2% (w/v) caused cell lysis and immediate (< 5 s) loss of light emission. Exposure to triclosan at lower concentrations caused a decrease in light output over time. The rate of the decrease in light output followed a cuboid relationship, of which the initial rate (first 60 s) of light loss was proportional to the concentration of triclosan. The effect on light output by two commercially available hygiene products containing triclosan also caused a similar response in light loss.
Mouse immunoglobulin (Ig) molecules have previously been shown to bind to the surface of CD5(+) B cells from patients with B-cell chronic lymphocytic leukemia (B-CLL). The results indicated that surface IgM was involved in the interaction and suggested the phenomenon was an example of the polyreactive binding capacity of the surface Ig (sIg) expressed by these malignant cells. This article describes the further characterization of the interaction between human IgM and mouse Ig molecules and subunits. Mouse Ig molecules of both kappa and lambda light chain classes bound to the B-CLL cell surface. The dissociation constant for the interaction of mouse IgG1 (K121) with the B-CLL cell surface was 3.6 x 10(-7) M. To confirm the involvement of the human IgM expressed by the B-CLL cells in the interaction, the malignant cells were stimulated in vitro to induce secretion of human IgM. Enzyme immunoassay was used to show that secreted human IgM bound to intact mouse Ig, as occurred with the cell surface analysis. The mouse Ig epitope recognized by the purified secreted human IgM was shown by Western blot analysis to be located on the light chain of the mouse Ig molecule and to be conformationally dependent. K121 light chain was cloned and expressed in E. coli and the recombinant light chain bound to the surface of CLL B cells. The results confirm that human IgM is the reactive ligand in the interaction with mouse Ig and indicate that the interaction of polyreactive IgM with mouse IgG occurs via the light chain component of IgG.
Ciprofloxacin, an orally-absorbed fluoroquinolone is effective against multiply resistant Pseudomonas aeruginosa in cystic fibrosis patients. It is the only practicable agent against extraintestinal salmonellosis and shigellosis in developing countries. However, concern with the risk of arthropathy in young children has restricted its use in pediatrics. Pharmacokinetic studies with ciprofloxacin are limited in the pediatric population. As a result, the dose and frequency of administration are not established in children. In this study the possibility of using salivary concentrations as surrogate measure of serum concentrations was investigated. A pediatric formulation of the drug (125 mg per capsule) was prepared and compared to 250 mg tablets. Relative bioavailability was 105% (tablet/capsule). The time to peak salivary concentration and elimination rate from saliva were significantly different from serum (p < 0.01 and p < 0.05 respectively). The linear regression analysis of post-peak concentrations in serum and saliva yielded a slope of 1.25 and correlation coefficient of 0.83. It was also found that salivary concentrations may be contaminated from drug retained in the oral cavity. The conclusion was drawn that salivary concentrations could not be reliably used as a surrogate measure of serum levels for therapeutic drug monitoring.
Hyperlipoproteinemia occurs commonly in diabetics and may contribute to early atherosclerosis in these patients. The effect of dietary carbohydrate restriction on lipid abnormalities has been examined in 42 newly diagnosed maturity-onset diabetics, in whom plasma lipoproteins were measured before treatment was started and at regular intervals during ten months of dietary therapy. Twenty-four patients (57%) had abnormal lipids when diabetes was first diagnosed. Nine were classed as Type II and 15 as Type IV hyperlipoproteinemia. Plasma lipids reverted to normal in half these patients after dietary treatment for one month. Only 8 diabetics (19%) showed persistent lipid abnormality after ten months' treatment: all had been unable to diet satisfactorily as judged by persisting obesity and hyperglycemia. The common lipoprotein abnormalities of maturity-onset diabetes can usually be returned to normal by the simplest possible carbohydrate-restricted diet, if patients adhere to this. Specialized and complex diets or lipid-lowering drugs are unncessary in the majority of patients.
We provide evidence for the presence of arginine vasopressin (AVP) in human fetal and neonatal skeletal muscle using a combination of specific RIA, tangential flow ultrafiltration and reverse-phase HPLC separation. The IR-AVP concentrations are negatively correlated with gestational age (r = -0.75, P less than 0.0001) and range from 1 to 10 pmol/g wet wt at 15 weeks gestation to 0.04 pmol/g wet wt at term. This IR-AVP substance is of low molecular weight (less than 3000 mol. wt), elutes in the same position as standard AVP after HPLC separation and is detected by four different anti-AVP antisera.
A 13-year-old girl with an unbalanced karyotype 45,XX,-15,der(22)t(15;22)(q13;q13.3) de novo had Prader-Willi syndrome (PWS), (score 13.5), but with features of mental and physical retardation more severe than usually seen in PWS. The clinical diagnosis of PWS was confirmed by methylation analysis that showed absence of the paternal band. With GTG banding, the cytogenetic breakpoint on chromosome 15q13, with 15q14 intact, encompassed the PWS region, while the breakpoint on 22q was terminal. Investigations with FISH utilised ten different probes/combinations, namely SNRPN/PML, TUPLE1/22q13.3, TUPLE/ARSA, GABRB3, three YAC clones and one cosmid for specific regions within chromosome 15q, painting probes for the long arm of chromosomes 15 and 22 and a pantelomere probe. Deletion of SNRPN,TYAC 9 (at 15q11-12), TYAC19 (at 15q13) and GABRB3 (within the PWS locus), was evident on the derivative (22) chromosome, while TYAC10 (at 15q22), cos15-5 (at 15q22) and PML (15q22) were not deleted. On the der(22), 22q13.3 and ARSA were not deleted, but the most distal non specific pantelomeric probe was deleted. Thus, the severe phenotype could be attributable to deletion on chromosome 15q extending beyond q13 to q14, (further than the usual chromosome 15q deletion (q11-13) in PWS), or be related to loss of the very terminal 22q region (from ARSA to the pantelomere) or be due to genetic factors elsewhere in the genome.
The association between the Sollerman test of hand grip and the Sequential Occupational Dexterity Assessment (SODA) and their relationship to impairment and subjective disability measures were examined. Twenty-five patients with rheumatoid arthritis affecting their hands participated in a clinical and subjective evaluation. Clinical evaluation included the use of the two hand function instruments and measurement of finger range of motion. Subjective evaluation was done by means of a patient questionnaire comprising 20 questions from the Health Assessment Questionnaire and by visual analog scales for rating pain severity and hand function. Results confirmed a strong association between the Sollerman test of hand grip and the SODA. Both instruments were found to correlate significantly with subjectively assessed hand function. Associations between the results of the two hand function tests and subjective pain and disability assessments in global daily tasks were weak. The SODA instrument more consistently correlated to the limitations in finger motion than did the Sollerman test of hand grip. This study demonstrates that the SODA and the Sollerman test of hand grip produce similar information under controlled conditions in this patient group despite their differences in conceptual development and measurement properties. A generalized measure such as the Health Assessment Questionnaire or the pain visual analog scale alone is insufficient to represent what patients can do with their hands in daily life.
A concentration gradient of the GTP-bound form of the GTPase Ran across nuclear pores is essential for the transport of many proteins and nucleic acids between the nuclear and cytoplasmic compartments of eukaryotic cells [1] [2] [3] [4]. The mechanisms responsible for the dynamics and maintenance of this Ran gradient have been unclear. We now show that Ran shuttles between the nucleosol and cytosol, and that cytosolic Ran accumulates rapidly in the nucleus in a saturable manner that is dependent on temperature and on the guanine-nucleotide exchange factor RCC1. Nuclear import in digitonin-permeabilized cells in the absence of added factors was minimal. The addition of energy and nuclear transport factor 2 (NTF2) [5] was sufficient for the accumulation of Ran in the nucleus. An NTF2 mutant that cannot bind Ran [6] was unable to facilitate Ran import. A GTP-bound form of a Ran mutant that cannot bind NTF2 was not a substrate for import. A dominant-negative importin-beta mutant inhibited nuclear import of Ran, whereas addition of transportin, which accumulates in the nucleus, enhanced NTF2-dependent Ran import. We conclude that NTF2 functions as a transport receptor for Ran, permitting rapid entry into the nucleus where GTP-GDP exchange mediated by RCC1 [7] converts Ran into its GTP-bound state. The Ran-GTP can associate with nuclear Ran-binding proteins, thereby creating a Ran gradient across nuclear pores.
4-Fluorobenzenesulfonyl chloride (fosyl chloride), due to the strong electron-withdrawing property of its fluoride atom, is found to be an excellent activating agent for the covalent attachment of biologicals to a variety of solid supports (e.g. functionalized polystyrene microspheres, Sepharose beads, or cellulose rods and hollow fibers). This reagent reacts rapidly with primary or secondary hydroxyl groups, at ambient temperature and pressure, to form 4-fluorobenzenesulfonate leaving groups. The activated solid support can be used immediately or preserved for several months without loss of activity by freeze-drying or by storage at 4 degrees C in aqueous solution at pH 5. Enzymes, antibodies, avidin, and other biologicals can be covalently attached to the activated solid phase with excellent retention of biological function. Potential therapeutic applications of the fosyl chloride chemistry for bioselective separation of human lymphocyte subsets from whole blood and tumor cells from bone marrow are presented.
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