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Biomedical subjects

A Childs

Publications and source records attributed to A Childs.

33 records · Page 2Linked to original sources

The development of anti-interleukin-2 antibodies in patients treated with recombinant human interleukin-2 (IL-2).

Approximately 65% (11/17) of cancer patients participating in an ongoing Phase I clinical trial with recombinant interleukin-2 developed nonneutralizing serum IgG anti-interleukin-2 antibodies within 1 month of initiating therapy. These antibodies could be detected using any of several standard techniques including immunoblots and enzyme-linked immunosorbent assays. Western blot analysis and retention experiments with protein A-Sepharose indicate that the antibodies are specific for interleukin-2. The interleukin-2 mutein utilized in this clinical trial (des-ala-ser125 r-IL-2) differs from the major species of the human T cell-derived lymphokine in that it lacks the N-terminal alanine of the native molecule, is not glycosylated, and possesses a serine-cysteine substitution at position 125. Another recombinant interleukin-2, identical to the mutein except that it retains the cysteine at position 125 (des-ala-cys125 r-IL-2), strongly competes with the mutein in competitive enzyme-linked immunosorbent assays, suggesting that the amino acid substitution is not responsible for the recognition of the molecule by serum antibodies. Conversely, nonrecombinant T cell-derived interleukin-2 fails to compete in these assays and is not retained by protein A-Sepharose columns when mixed with high-titer antiserum. These results suggest that the anti-interleukin-2 serum antibodies generated in the course of treatment do not react with the nonrecombinant lymphokine but recognize epitopes peculiar to recombinant forms which are not dependent on the amino acid substitution at position 125. The failure of the antibodies to neutralize the biological activity of recombinant interleukin-2 (IL-2) in lymphocyte proliferation assays and to bind to the native lymphokine suggests that they may not affect IL-2-dependent cellular immune functions in vivo.

Antibody Formation↗

Effect of posture on vital capacity.

The influence of some extreme body postures on vital capacity (VC) was examined in young adult humans. Two postures required full support of body weight by the arms: arms up, hanging from a bar, and arms down with hands gripping parallel bars. Three involved muscles that flex and extend the trunk: a partial sit-up position while supine and nearly maximal spinal extension and flexion while standing. Changes at the inspiratory and expiratory volume extremes were recognized by having the subjects do two VC efforts: the first standing and the second in the posture in question while continuing to breathe on the spirometer. Control observations in which the second of a VC pair was performed in an unstressed posture allowed correction for the influence of rebreathing. The changes in corrected VC were small, the greatest being an average reduction of approximately 8% in the partial sit-up position. During full support of body weight by the arms, the VC was slightly increased due to a significant increase in the inspiratory extreme and no change in the expiratory extreme. Spinal extension produced small increases in lung volume at both extremes with no significant change in VC, whereas spinal flexion did not influence the upper extreme but did increase lung volume at the lower extreme. The changes are discussed in terms of trunk muscle action.

Adolescent↗

Scopolamine effects in vestibular defensiveness.

Disturbed vestibular function secondary to brain stem injury may result in postural gravitational insecurity, and aversion reactions or intolerance to movement. The Transderm scopolamine disc was applied in a double-blind, placebo-controlled study of five post-head-injury patients who underwent provocative vestibular stimulation such as turning in a wheelchair, head shaking, and the log roll. Four of the patients showed improvement in exquisite sensitivity to rotational movement. A surprise finding of improved truncal stability in two of the more severely injured patients indicates a potential usefulness of the scopolamine patch for patients with truncal ataxia.

Brain Injuries↗

Thermal denaturation of alpha 1-protease inhibitor. Stabilization by neutral salts and sugars.

Alpha 1-protease inhibitor (alpha 1 PI), also called alpha 1-antitrypsin, may be useful for replacement therapy in a number of chronic or acute disorders. The risk associated with the possible presence of hepatitis virus can be greatly reduced by pasteurization at 60 degrees C for 10 h. A series of thermal denaturation profiles was obtained in the presence of various protein stabilizers using the increase in 1,8-anilinonaphthalene sulfonate fluorescence that accompanies protein denaturation. A parallel series of experiments was conducted to evaluate each additive for its capacity to protect the biological activity of alpha 1 PI. As much as 92% of the inhibitory activity against elastase and trypsin could be recovered after pasteurization in buffer containing citrate (1.2 M) and either EDTA (0.5 M) or gluconate (1.2 M). Loss of activity was not affected by protein concentration. In conclusion, conditions have been developed to protect the bulk of alpha 1 PI from denaturation during pasteurization, and this should give an added impetus to efforts to test the efficacy of this protein in various clinical conditions.

Anilino Naphthalenesulfonates↗

Studies of primate protein variation and evolution: microelectrophoretic detection.

Genetic variation at 16 protein and enzyme loci in Ceropithecus aethiops and several other primate species has been surveyed, using cellulose acetate microelectrophoresis. Resolution of several standard variant proteins is comparable to that achieved on starch gel or polyacrylamide gel. Although both intraspecific and interspecific variation was observed for some loci, the data generally support the concept that extracellular proteins are more likely to be polymorphic within a species, while intracellular proteins generally vary between species, if at all. These methodologies are particularly appropriate for screening multiple-locus variation in large numbers of samples; their relevance to studies of molecular evolution and evaluation of theories of kin selection is discussed.

Animals↗

Acute symbiotic psychosis in a postoperative transsexual.

An unexpected complication of sex-reassignment surgery in a 23-year-old male-to-female transsexual is presented. Having been periodically depressed but never psychotic before surgery, the patient experienced an acute decompensation 3 days after operation. Symptoms of this time-limited illness included hallucinations and wish-fulfilling delusions, but most prominent was the demand to be in continuous contact with other people. Historical data revealed a symbiotic relationship with the grandmother ending precipitously with her death when the patient was 6. It is hypothesized that the unresolved grief reappeared after the surgery, owing to the unconscious linkage between becoming "female" and regaining the lost symbiotic object. Recompensation, possibly through the use of another person as a transitional object, was noted during the illness. This was felt to be a repetition of the pattern of reaction to previous losses.

Adult↗

Naltrexone in organic bulimia: a preliminary report.

Multiple lines of experimental evidence point to the involvement of endogenous opiates in appetite regulation. Post brain injury patients often exhibit driven eating behaviour. Since this problem fails to respond to behaviour modification, appetite suppressants, lithium, or any other usual approach, the use of the oral narcotic antagonist, Naltrexone, was given to three such patients. Naltrexone binds multiple opiate receptor sites in the hypothalamus, including the kappa receptors which have been implicated in appetite regulation, the use of this narcotic antagonist in hypothalamic hyperphagia appears to be a rational approach to this intractable problem. In this open trial, lasting from 4 1/2 to 9 months, the minimal effective dose appeared to be in the range of 100 mg per day. No side-effects (for example elevations in liver enzymes) were noted. All of the patients had an improved sense of well-being and their behaviours were less difficult to manage when on the Naltrexone. The significance of this preliminary trial is that narcotic antagonists may have a role in the treatment of brain-injured patients with bulimia. Also, Naltrexone may be useful in treating other maladaptive behavioural consequences of head trauma such as stealing, manipulation, demandingness, and depression. Likewise, the effects on the deranged endocrine system, such as the hypogonadism, are significant and deserve further exploration.

Adolescent↗

The PLEXUS parameters: results of the 'PLEXUS conference'.

Presentations by experts at an international conference on coma and persistent vegetative state (PVS) identified 32 parameters of varying prognostic significance that can be determined in this patient population. These parameters are tabulated for heuristic purposes and to summarize a portion of the information exchanged at this conference.

Brain Damage, Chronic↗

Fifteen-cycle cranial electrotherapy stimulation for spasticity.

Severe post-anoxic spasticity in a 25-year-old female was significantly improved during an open trial of 15 cycle per second CES. The bipolar LISS device with suboccipital electrode placement was used for 40 minutes three times a day. A synergism appeared when dantrolene 50 mg twice a day was combined with the CES, these additive effects being greater than either modality used alone.

Brain Damage, Chronic↗