A new design of vehicle seat intended to alleviate lower back pain.
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Automobiles↗
Biomedical subjects
D A Johnson
Publications and source records attributed to D A Johnson.
Respiratory symptoms, lung function, and sensitisation to flour in a British bakery.
A survey of dust exposure, respiratory symptoms, lung function, and response to skin prick tests was conducted in a modern British bakery. Of the 318 bakery employees, 279 (88%) took part. Jobs were ranked from 0 to 10 by perceived dustiness and this ranking correlated well with total dust concentration measured in 79 personal dust samples. Nine samples had concentrations greater than 10 mg/m3, the exposure limit for nuisance dust. All participants completed a self administered questionnaire on symptoms and their relation to work. FEV1 and FVC were measured by a dry wedge spirometer and bronchial reactivity to methacholine was estimated. Skin prick tests were performed with three common allergens and with 11 allergens likely to be found in bakery dust, including mites and moulds. Of the participants in the main exposure group, 35% reported chest symptoms which in 13% were work related. The corresponding figures for nasal symptoms were 38% and 19%. Symptoms, lung function, bronchial reactivity, and response to skin prick tests were related to current or past exposure to dust using logistic or linear regression analysis as appropriate. Exposure rank was significantly associated with most of the response variables studied. The study shows that respiratory symptoms and sensitisation are common, even in a modern bakery.
Adult↗
Hypothalamic disease in association with dysgenesis of the corpus callosum.
We describe two cases of dysgenesis of the corpus callosum demonstrated by magnetic resonance. The first patient presented with chronic hyponatraemia. Investigation demonstrated re-setting of the osmoreceptor and thirst centres. The calculated threshold for arginine vasopressin (AVP) release was reduced at 252 mosmol/kg while severe thirst was perceived at a plasma osmolality of 260 mosmol/kg. Insulin-induced hypoglycaemia produced an exaggerated AVP response. The second patient presented with hypothermia. The calculated threshold of AVP release was 296 mosmol/kg with increased sensitivity of AVP response to hypertonic saline. The plasma AVP response to insulin-induced hypoglycaemia was absent. Both cases had normal anterior pituitary function and psychological assessment showed a similar prefrontal defect. Specific tests of callosal function were normal. These cases illustrate the importance of undertaking complete neuroradiological assessment of cases of unexplained hypothalamic disease regardless of the age of presentation to avoid overlooking this rare congenital association.
Adolescent↗
Comments on the Northwick Park 'Functional' Psychosis Study.
"Functional psychosis is conventionally subdivided into schizophrenia and manic depressive psychosis. Response to treatment is assumed to be a validating criterion for these diagnoses. The efficacy of pimozide (a dopamine antagonist neuroleptic), lithium, and a combination of the two was compared with that of placebo in a 4-week trial in 120 functionally psychotic patients, each of whom was assessed for psychotic symptoms, manic symptoms, and depressive symptoms. The sample was subdivided into patients with predominantly elevated mood, predominantly depressed mood, and no consistent mood change. Pimozide reduced psychotic symptoms in all groups of patients. The only significant effect of lithium was to reduce elevated mood. Thus dopamine blockade seems relevant to the resolution of psychotic symptoms in all types of 'functional' psychosis, but the mode of action of lithium in psychotic patients concerns only mood. Application of standardised classifications of functional psychosis to these data did not change this conclusion."
Bipolar Disorder↗
Pulmonary disease in progressive systemic sclerosis. A complication of gastroesophageal reflux and occult aspiration?
Thirteen patients with progressive systemic sclerosis were studied to evaluate the possible role of gastroesophageal reflux as a contributing pathogenic factor in the pulmonary disease of the patients. The evaluation of all patients included fiberoptic esophagogastroduodenoscopy with biopsies of the esophagus, otolaryngologic evaluation, technetium Tc 99m sulfur colloid aspiration scan, pulmonary function testing, including the diffusing capacity for carbon monoxide (DLCO) test, and 24-hour intraesophageal pH monitoring with probes placed 5 and 15 cm above the lower esophageal sphincter. Eleven patients had microscopic and macroscopic evidence of proximal esophagitis, 12 patients had laryngeal changes suggestive of aspiration, and 12 patients had abnormal DLCO values. Using multiple regression analysis, the degree of DLCO impairment correlated with the proximal and distal reflux episodes and scores recorded by pH monitoring. There was direct and indirect evidence for proximal gastroesophageal reflux and aspiration in the majority of patients, and a distinct correlation between the severity of reflux and the severity of pulmonary disease. Aggressive antireflux therapy may be helpful in reducing the pulmonary damage due to aspiration in these patients.
Adult↗
Tissue distribution and cellular location of the antigens recognized by human monoclonal antibodies 16.88 and 28A32.
Results from a previous study (M. V. Haspel et al., Cancer Res., 45: 3951-3961, 1985) indicated that it was possible to isolate a high proportion of human monoclonal antibodies reactive with cell surface, tumor-associated antigens when the hybridomas were obtained from fusions utilizing peripheral blood lymphocytes from patients immunized with autologous tumor cells. The assignment of membrane reactivity was made from immunoperoxidase studies which used air-dried, nonpermeabilized Cytospin preparations of colon tumor cells. Tumor specificity was assessed by immunohistological assays by using frozen sections of normal and malignant human tissues. We now describe a series of studies using two of these antibodies, 16.88 and 28A32, in which further information was obtained concerning the tumor specificity and cellular location of the target antigens reactive with these monoclonal antibodies. Data were acquired from a variety of experimental techniques which included quantitative and qualitative immunofluorescence on live and permeabilized cells, RBC-rosetting assays, immunoperoxidase studies on Cytospin and frozen tissue sections, and immunoblot procedures. These studies show that the 16.88 and 28A32 human monoclonal antibodies bind to antigens which (a) are located in the cell cytoplasm and are not expressed in detectable levels on the cell surface, and (b) are found in many normal and malignant cell types.
Antibodies, Monoclonal↗
Resonance Raman spectroscopy indicates a lysine as the sixth iron ligand in cytochrome f.
The resonance Raman spectrum of turnip cytochrome f is similar to that of other c-type cytochromes with the exception of a single band at 1532 cm-1 which is shifted to lower frequency relative to its position (1542-1545 cm-1) in other c-type cytochromes. Comparison of the frequency of this band with that in alkylated cytochrome c at high pH suggests that the sixth heme iron ligand in cytochrome f is a deprotonated lysine amino group rather than a methionine sulfur. Comparison of the amino-acid sequences of cytochromes f and c1 suggests lysine-145 as a likely candidate for the sixth heme iron ligand in cytochrome f.
Amino Acid Sequence↗
Determination of intrinsic membrane transport parameters from perfused intestine experiments: a boundary layer approach to estimating the aqueous and unbiased membrane permeabilities.
A boundary layer approach is developed for estimating the aqueous resistance in a perfused rat intestine experiment. Knowing the aqueous resistance allows the membrane surface concentration to be calculated as a function of the perfusate inlet concentration and perfusional flow rate. Determination of membrane uptake as a function of the membrane surface concentration rather than the perfusate concentration gives the intrinsic, unbiased membrane parameters for the uptake mechanism of Michaelis-Menten-type kinetics in parallel with passive diffusion. The aqueous resistance derived in the analysis is verified by comparison with flux data for 1-leucine and progesterone measured at various flow rates and intestinal lengths. The approach allows for a direct estimate to be made of the unbiased membrane permeability parameters.
Animals↗
Membrane permeability parameters for some amino acids and beta-lactam antibiotics: application of the boundary layer approach.
The boundary layer approach to analyzing the results of the perfused intestinal segment method of measuring membrane permeabilities is applied to the amino acids; leucine, valine, phenylalanine, lysine and aspartic acid and the beta-lactam antibiotics, cephalexin and penicillin V. The analysis indicates that in determining the membrane parameters, Pw vs. Cw data are preferable to using Jss = PwCw vs. Cw data. It is further shown that the carrier permeability, Pc* = Jmax*/Km, may be the most significant parameter to consider since luminal amino acid or drug concentration may generally be below the Km value. A comparison of P*c values for the beta-lactams with results for passively absorbed compounds indicates that the cephalosporins would be expected to be well absorbed orally based on the perfusion results. This suggests that this approach may be useful in estimating oral drug absorption for compounds that are absorbed passively as well as by a carrier-mediated mechanism.
Amino Acids↗
Purification and characterization of four monofluorescein cobra alpha-toxin derivatives.
We labeled cobra-alpha-toxin (Naja naja siamensis 3) with near stoichiometric quantities of fluorescein isothiocyanate. To reduce labeling of the hyperreactive N epsilon-lysine 23, the alpha-toxin was modified reversibly with citraconic anhydride before fluorescein labeling. The citraconic anhydride was later removed with strong acid, and four of the six possible monofluorescein alpha-toxin derivatives were isolated by isoelectric focusing on an immobilized pH gradient. Thermolysin digestion and subsequent high pressure liquid chromatography of the peptides yielded one dominant fluorescent peak from three of the isolated monofluorescein derivatives. Sequence analyses of these three fluorescent peaks indicated monofluorescein labeling at Lys-69, Lys-35, and Lys-49. Since one derivative (not identified by sequence analysis) displayed essentially identical chromatographic, spectroscopic, and binding properties as our previously identified monofluorescein-Lys-23 toxin (Johnson, D. A., and Taylor, P. (1982) J. Biol. Chem. 257, 5632-5636), we identified the site of labeling of this fourth derivative to be Lys-23. While only small differences were observed in the extinction maxima and molar extinction coefficients, the quantum yields of the isolated derivatives varied markedly and ranged between 0.18 and 0.41. Binding of monofluorescein-Lys-69, -Lys-35, -Lys-49, and -Lys-23 derivatives to the membrane-associated acetylcholine receptor from Torpedo californica was associated with -39, -26, -9, and +96% changes in fluorescence emission intensity, respectively. Based on analyses of the kinetics of fluorescence changes associated with receptor binding, the association and dissociation rate constants were measured. Relative to native cobra alpha-toxin, monofluorescein conjugation reduced the bimolecular association rate constants for binding to the receptor 13-33-fold. The dissociation rate binding rate constants were less affected and were reduced 0-5-fold.
Amino Acid Sequence↗
Observations on the use of depot neuroleptics in schizophrenia.
This paper reviews some of the advantages and disadvantages of long-term maintenance therapy with neuroleptics in schizophrenia. The need to separate first-illness schizophrenia from chronic schizophrenia is illustrated. The reduction in the risk of a further acute relapse with continued medication and the likely duration of maintenance therapy are discussed. The true meaning of a further relapse to the patient in terms of reduced social and work function is also discussed. The advantages of using long-acting depot injections for drug administration are stressed. The complex issue of the correct dosage for maintenance is reviewed, with no proven advantage for either very high doses or very low doses. The frequency of depressive symptoms in schizophrenia is reviewed and the possible aetiologies discussed. The decision to use short- or long-term drug therapy, and whether to use a particular method of drug administration (oral or long-acting depot injections) should be separate issues. Depot injections may, on occasions, be the appropriate method of drug administration for short-term therapies, just as oral drugs have a place in the longer-duration maintenance treatments.
Animals↗
In vivo antitumor activity demonstrated with squamous carcinoma reactive monoclonal antibody-Vinca immunoconjugates.
An immunoconjugate (PF1/D-DAVLBHYD), made with the squamous carcinoma reactive monoclonal antibody PF1/D and a derivative of vinblastine, DAVLBHYD, was shown to suppress established T222 human tumor nude mouse xenografts using a multidose protocol. Treatments of xenograft-bearing mice with free drug, free antibody, or a mixture of the two, were unsuccessful at achieving suppression without associated toxicity, using otherwise identical protocols. A Vinca conjugate with a related squamous carcinoma reactive monoclonal antibody, PF1/B, was shown to have similar tumor suppressive activity. In a dual immunoconjugate therapy protocol, PF1/D-DAVLBHYD and PF1/B-DAVLBHYD had additive antitumor effects which were consistent with their complementary tumor reactivity.
Animals↗
4-Hydroxybutyric aciduria in a patient without ataxia or convulsions.
A child presenting with mild psychomotor retardation, hypotonia, microcephaly and hyperkinesis is described. Urinary organic acid analysis by combined gas chromatography-mass spectrometry revealed 4-hydroxybutyric aciduria. Succinic semialdehyde dehydrogenase activity in extracts of white cells derived from the patient was less than 10% of control values.
Ataxia↗
Bronchial leukocyte proteinase inhibitor: hydrodynamic properties and interaction with alpha 2-macroglobulin-bound elastase.
Bronchial leukocyte proteinase inhibitor (BLPI) is an 11.7 kDa, acid-stable protein found in mucous secretions, which inhibits neutrophil elastase. The Stoke's radius of BLPI calculated from sedimentation equilibrium and sedimentation velocity centrifugation data was in good agreement with the value determined by gel filtration. These data indicate that BLPI exists in a compact globular conformation at both neutral and acidic pH. BLPI, due to its small compact size, can inhibit neutrophil elastase after the enzyme has been complexed with alpha 2-macroglobulin (A-2-M) but alpha 1-proteinase inhibitor failed to inactivate A-2-M-bound elastase. The apparent association rates of BLPI and Eglin C with A-2-M-bound elastase were found to be 6.3 X 10(2) M-1s-1 and 1.1 X 10(3) M-1s-1, respectively. These apparent association rates decreased 168-fold for BLPI and 909-fold for Eglin C, relative to the association rates of these inhibitors with free elastase. These changes probably result from a combination of effects, such as inhibitor accessibility to the enzyme and/or reaction rate, but regardless of the mechanism these data suggest that BLPI may function to control both free and A-2-M-bound elastase.
Bronchi↗
Changes in rat parotid saliva protein composition following chronic reserpine treatment and their relation to inanition.
Chronic administration of the catecholamine-depleting agent, reserpine (0.5 mg/kg), resulted in a reduction in food intake after 3 days. To differentiate effects of the drug from those of reduced food intake a pair-fed group, whose daily caloric intake was restricted to the amount consumed by the reserpine-treated rats, was included. After 7 days, both the reserpine-treated and pair-fed control exhibited a marked reduction in the volume of saliva collected in a 30 min interval following a secretory stimulus compared to untreated ad libitum-fed controls, and the proportion of salivary proteins attributable to acidic and basic proline-rich proteins and to minor 1b protein were decreased whereas deoxyribonuclease was increased. For two of the salivary proteins (fractions I and V) changes for the reserpine-treated and pair-fed groups were different. Fraction I was reduced in both groups, but exhibited a greater decrease in the pair-fed than in the reserpine-treated, whereas fraction V was significantly increased only in the pair-fed group. Thus many of the salivary changes associated with reserpine treatment may have resulted from the change in feeding habits and not from reserpine treatment per se. The study demonstrates the importance of controlling for food intake under experimental circumstances which may lead to a marked change in daily feeding habits.
Animals↗
Human kininogens.
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Chromatography, Affinity↗
Construction of transposons carrying the transfer functions of RP4.
The transfer genes and origin of transfer of the wide host range plasmid RP4 have been cloned into the transposons Tn1 and Tn5. The newly constructed transposons can be used to mutagenize bacterial plasmids or the chromosome in species such as Escherichia coli or Rhizobium. It is then possible to mobilize the plasmid or chromosome using the transfer functions provided in cis by the transposon. These constructs may aid chromosome mapping in many gram-negative species by allowing the wider use of the RP4 conjugal transfer system combined with the potential ability to select the site of insertion and thus the site of the origin of transfer.
Chromosomes, Bacterial↗
Mitochondrial DNA variation among geographical populations of the screwworm fly, Cochliomyia hominivorax.
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Animals↗