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Biomedical subjects

J Chandler

Publications and source records attributed to J Chandler.

At least 73 records · Page 4Linked to original sources
PubMed1990

Functional reach: a new clinical measure of balance.

A new clinically accessible measure of balance, functional reach (FR), is the difference between arm's length and maximal forward reach, using a fixed base of support. The purposes of this study were to (a) establish FR as a measure of the margin of stability versus the laboratory measure, center of pressure excursion (COPE); (b) test reliability and precision, and (c) determine factors that influence FR, including age and anthropometrics. We evaluated FR in 128 volunteers (age 21-87 years). FR was determined with a precise electronic device and a simple clinical apparatus (yardstick). FR correlates with COPE (Pearson r = .71) and is precise (coefficient of variation = 2.5%) and stable (intraclass correlation coefficient across days = .81). Age and height influence FR. FR is portable, inexpensive, reliable, precise, and a reasonable clinical approximator of the margin of stability. FR may be useful for detecting balance impairment, change in balance performance over time, and in the design of modified environments for impaired older persons.

Adult↗
PubMed1990

Electromyographic analysis of postural adjustments in two methods of balance testing.

The primary purpose of this study was to compare postural responses during two methods of balance testing: 1) a platform perturbation test (PP), with destabilizing forces of uniform magnitude given at the base of support, and 2) a postural stress test (PST), with destabilizing forces of increasing magnitude given at the waist. A secondary purpose was to examine the relationship between balance strategy scores and the patterns of muscle responses as determined by electromyographic analysis on the PST. Postural responses to backward sway of 17 healthy subjects, aged 60 to 79 years (means = 69.0, s = 5.3), were characterized bilaterally by EMG recording of the tibialis anterior, quadriceps femoris, gastrocnemius, and hamstring muscles. We examined three measures of bilateral postural responses: 1) latency to first muscle response (FR) among the four lower extremity muscle groups, 2) tibialis anterior muscle latency (TA), and 3) patterns of muscle responses. Our results demonstrated significantly shorter (p less than .001) TAs and FRs (in milliseconds) on the PST than on the PP (PST TA: = means = 80.3, s = 12.4; PP TA: = means = 142.6, s = 13.4; PST FR: means = 75.9, s = 10.4; PP FR: = means = 140.4, s = 13.6). The ankle strategy was the most frequently used pattern of muscle response during both the PP and the PST, but it occurred less frequently on the PST than on the PP (PP = 72.5%, PST = 50.9%) (p less than .05). No consistent relationship was observed between the balance strategy scores as determined by videotape analysis of the PST and the patterns of muscle responses as determined by EMG analysis.

Aged↗
PubMed1987

Cancer risk-assessment models: anticipated contributions from biochemical epidemiology.

Uncertainties in quantitative assessment of cancer risk limit the scientific role of this activity in the policy and regulatory debate on cancer control. Risk-assessment strategies and models are highly dependent on the nature and quality of the data available. However, accumulating laboratory and epidemiologic studies that are shedding new light on mechanisms of carcinogenesis have not yet been integrated into current risk-assessment models. Future developments in risk assessment may, therefore, be anticipated by considering the type of epidemiologic data that may soon be generated. Three important areas of epidemiologic and biochemical research should reduce some of the uncertainty in quantitative risk assessment by making it possible to: identify stages of the disease process through precursor lesions, biochemical markers, and to determine at which stage the carcinogen acts; identify subpopulations that are at enhanced or reduced susceptibility to carcinogenic influences; and obtain additional and refined indices of dose. Much of this research is being called "biochemical epidemiology." Strategies for incorporating these newly generated data into regulatory decisions vary from developing new mechanistically based mathematical models to applying existing models to biologically distinct subpopulations.

Carcinogens↗
PubMed1987

The significance of stable patients with sternal fractures.

A retrospective review of patients admitted with sternal fractures without massive trauma to the chest or hypotension was undertaken. Chest pain was present in 59 of 60 patients while external signs of bruising were noted in one-third. The standard anteroposterior (AP) roentgenogram of the chest was diagnostic in all patients. Thirty-four (56.7 per cent) patients had 51 significant noncardiac injuries, an average of 1.5 injuries per patient. Most commonly, these were orthopedic injuries, fractures of the rib and closed head injuries. Sixty-two per cent of the patients with sternal fractures had abnormal electrocardiograms (ECG) at some time, of which 34 per cent had ECG changes consistent with ischemia. The admission ECG was normal in 20 (48 per cent) patients. Three of these patients subsequently had significant ECG changes. Fractures that were comminuted or involved the sternal angle were more likely to be associated with ECG abnormalities than were simple fractures of the sternal body. Only three patients had elevated creatine phosphokinase-myocardial bond fractions. Two dimensional echocardiography and biventricular radionuclide angiocardiography were normal in 11 patients, including five patients with ECG abnormalities. There were no deaths related to the sternal fractures per se or to associated injuries. Sternal fractures result from high energy trauma and should be suspected in patients with chest pain after blunt thoracic trauma. The lateral roentgenogram of the chest is the most useful diagnostic test. There is a high incidence of associated cardiac and noncardiac injuries in these patients mandating close observation with ECG monitoring in the intensive care unit.

Adolescent↗
PubMed1985

Prospective, randomized comparison of the efficacy and safety of netilmicin-clindamycin and tobramycin-clindamycin in the treatment of serious systemic infections.

Fifty-three patients with documented or suspected mixed flora infections were randomly assigned to receive either netilmicin or tobramycin in combination with clindamycin. Data from 36 patients with 43 documented infections yielding 102 clinical isolates were evaluated for efficacy. In the 18 patients receiving netilmicin-clindamycin, 90% of the infections responded favorably and 96% of the pathogens were eliminated. In the 18 patients receiving tobramycin-clindamycin, 81% of the infections resolved and 88.5% of the pathogens were eliminated. Forty-nine patients were included in the safety analysis. The incidence of nephrotoxicity was similar in both groups (netilmicin, 20%; tobramycin, 21%). Auditory toxicity occurred less frequently in the netilmicin-clindamycin group (4.5%) than in the tobramycin-clindamycin group (21.7%). These results demonstrate that both the netilmicin-clindamycin and the tobramycin-clindamycin combinations are comparable in efficacy and in potential for causing nephrotoxicity. In this study, however, netilmicin was considerably less ototoxic than tobramycin.

Adolescent↗
PubMed1983

Inhibition of fast- and slow-phase depolarization-dependent synaptosomal calcium uptake by ethanol.

Uptake of 45Ca++ by synaptosomes isolated from cerebral cortex, cerebellum, midbrain and brain stem of male, Sprague-Dawley rats was measured at 1-, 3-, 5-, 15-, 30- and 60-sec time periods. At 1 sec, the Ca++ uptake rate by cerebrocortical synaptosomes was 1.45 mumol/sec/g of protein, whereas the 60-sec rate was 0.03 mumol/sec/g of protein. In vitro addition of ethanol, 80 mM, inhibited depolarization-dependent (65 mM KCl) 45Ca++ uptake by synaptosomes but the time-response relationships varied depending upon the brain region studied. In cerebrocortical synaptosomes, ethanol significantly inhibited only the fast-phase component of 45Ca++ uptake (1 and 3 sec). Ethanol inhibited 45Ca++ uptake by midbrain synaptosomes at all measurement times studied (1, 3, 5 and 15 sec), whereas in cerebellum and brain stem ethanol inhibited 45Ca++ uptake at 3- and 5-sec time periods. Ethanol at concentrations of 25, 50, 100 and 150 mM inhibited 45Ca++ uptake by 9.0, 15.9, 24.8 and 30.7%, respectively, in cerebrocortical synaptosomes. In vitro ethanol, 80 mM, added to cerebrocortical synaptosomes isolated from rats fed a nutritionally adequate liquid ethanol diet did not significantly inhibit depolarization-dependent 45Ca++ uptake. The results of this study show that pharmacologically relevant ethanol concentrations inhibit voltage-dependent 45Ca++ uptake into synaptosomes. This inhibitory action may, at least in part, underlie some of the intoxicating effects of ethanol. In addition, chronic administration of ethanol resulted in an apparent adaptive response such that addition of ethanol no longer blocked 45Ca++ uptake. This adaptive response involving the calcium channel may represent a cellular mechanism for functional tolerance development.

Animals↗
PubMedDate not supplied

IL2-ricin fusion toxin is selectively cytotoxic in vitro to IL2 receptor-bearing tumor cells.

Fusion toxins consist of peptide ligands linked through amide bonds to polypeptide toxins. The ligand directs the molecule to the surface of target cells and the toxin enters the cytosol and induces cell death. Ricin toxin is an excellent candidate for use in fusion toxins because of its extreme potency, the extensive knowledge of its atomic structure, and the years of experience with RTA chemical conjugates in clinical trials. We synthesized a baculovirus transfer vector with the polyhedrin promoter followed sequentially from the 5' end with DNA encoding the gp67A leader sequence, the tripeptide ADP, IL2, another ADP tripeptide, and RTB. Recombinant baculovirus was generated in Sf9 insect cells and used to infect Sf9 cells. Recombinant IL2-RTB protein was recovered at high yields from day 5 insect cell supernatants, partially purified by affinity chromatography, and characterized. The recombinant product was soluble and immunoreactive with antibodies to RTB and IL2, bound asialofetuin and lactose, and reassociated with RTA. In the presence of lactose to block galactose-binding sites on RTB, the IL2-RTB-RTA heterodimer was selectively cytotoxic to IL2 receptor, bearing cells. Specific cytotoxicity could be blocked with IL2. Thus, we report a novel targeted plant toxin fusion protein with full biological activity.

Animals↗
PubMedDate not supplied

Characterization of single site ricin toxin B chain mutants.

DNA encoding ricin B chain was modified by site-directed mutagenesis, and eight separate mutant RTB cDNAs including four novel mutants were ligated into the baculovirus transfer vector, pAcGP67A. Cotransfection of S. frugiperda Sf9 cells with BaculoGold DNA was followed by limiting dilution isolation of recombinant baculoviruses. Infection of Sf9 cells at a multiplicity of infection of 5 in the presence of 25 mM lactose produced 0.05-1 mg/L of soluble, glycosylated 34 kDa proteins immunoreactive with monoclonal and polyclonal antibodies to ricin B chain. Mutant ricin B chains were partially purified by monoclonal antibody immunoaffinity chromatography to 10-50% purity in near milligram quantities. The mutant ricin B chains had decreased lectin binding relative to plant ricin B chain as measured by binding to immobilized lactose and asialofetuin and cell binding immunofluorescence. The mutant ricin B chains reassociated with plant RTA similarly to plant RTB, and the recombinant heterodimers had slightly reduced cell cytotoxicity relative to ricin.

Animals↗
PubMedDate not supplied

Double-lectin site ricin B chain mutants expressed in insect cells have residual galactose binding: evidence for more than two lectin sites on the ricin toxin B chain.

Ricin toxin, the heterodimeric 65 kDa glycoprotein synthesized in castor bean seeds, contains a cell binding lectin subunit (RTB) disulfide linked to an RNA N-glycosidase protein synthesis-inactivating subunit (RTA). Investigations of the molecular nature of the lectin sites in RTB by X-ray crystallography, equilibrium dialysis, chemical modification, and mutational analysis have yielded conflicting results as to the number, location, and affinity of sugar-combining sites. An accurate assessment of the amino acid residues of RTB involved in galactose binding is needed both for correlating structure-function of a number of plant lectins and for the design and synthesis of targeted toxins for cancer and autoimmune disease therapy. We have performed oligonucleotide-directed mutagenesis on cDNA encoding RTB and expressed the mutant RTBs in insect cells. Partially purified recombinant proteins obtained from infected cell supernatants and cell extracts were characterized as to yields, immunoreactivities, asialofetuin binding, cell binding, ability to reassociate with RTA, and recombinant heterodimer cell cytotoxicity. Two single-site mutants (subdomain 1 alpha or 2 gamma) and two double-site mutants (subdomains 1 alpha 2 gamma) were produced and studied. Yields varied by two logs with lower recoveries of double-site mutants. All the mutants showed immunoreactivity with a panel of anti-RTB monoclonal and polyclonal antibodies. Single-lectin site mutants displayed up to a 1 log decrease in asialofetuin binding avidity, while the double-site mutants showed close to a 2 log decrease in sugar binding. However, for each of the double-site mutants, residual sugar binding was demonstrated to both immobilized asialofetuin and cells, and this binding was specifically inhibitable with alpha-lactose. All mutants reassociated with RTA, and the mutant heterodimers were cytotoxic to mammalian cells with potencies 1000-fold or more times that of unreassociated wild-type RTA or RTB. These data support a model for three or more lectin binding subdomains in RTB.

Binding Sites↗