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Biomedical subjects

J Davis

Publications and source records attributed to J Davis.

At least 415 records · Page 23Linked to original sources

Nonproductive kappa immunoglobulin genes: recombinational abnormalities and other lesions affecting transcription, RNA processing, turnover, and translation.

Six nonproductive kappa immunoglobulin genes (kappa- alleles) were cloned and sequenced. The structural abnormalities discerned from sequence analysis were correlated with functional lesions at the level of transcription, RNA processing, turnover, and translation. Four kappa- alleles, three containing V kappa genes and one not, are transcribed at normal or even greater than normal rates, the defects in these genes being expressed at various posttranscriptional levels. The other two kappa- alleles, both of which lacked V genes, exhibited greatly depressed yet clearly detectable transcriptional activity. These results are consistent with a hierarchical relationship between enhancer and promoter elements in which the enhancer establishes transcriptional competence at the kappa locus and the promoter (or pseudopromoter) determines the relative level of transcriptional activity. One of the structural abnormalities discovered in this study, a large deletion which removes the entire J kappa region, also provides new insight into the mechanism of VJ and VDJ recombination.

Alleles↗

Acute tolerance development to the cardiovascular and subjective effects of cocaine.

Eight normal adult volunteer subjects received an intranasal pretreatment of either 4 (placebo) or 96 mg of cocaine. Sixty minutes later 16, 32 or 48 mg of cocaine was injected i.v. Cocaine plasma levels were determined periodically over a 2-hr period and both cardiovascular effects and verbal report of drug effects were monitored for 8 hr daily. The plasma concentrations of cocaine were always related to the dose administered. When i.v. cocaine was given after a 96-mg intranasal pretreatment, the increase in heart rate was not as great as when an i.v. injection followed a 4-mg inhalation. Comparable changes were obtained in subjective effects as measured on the Addiction Research Center Inventory, the Profile of Mood States and a subjective effects questionnaire. These results suggest that there is a decrease in physiological and subjective effects of cocaine when administered repeatedly in humans. This acute tolerance appeared to have dissipated within 24 hr.

Adult↗

Somatosensory evoked potentials (SEPs) and cortical single unit responses elicited by mechanical tactile stimuli in awake monkeys.

The origins of surface recorded evoked potentials have been investigated by combining recordings of single unit responses and somatosensory evoked potentials (SEPs) from the postcentral gyrus of 4 alert macaque monkeys. Responses were elicited by mechanical tactile stimuli (airpuffs) which selectively activate rapidly adapting cutaneous mechanoreceptors, and permit patterned stimulation of a restricted area of skin. Epidurally recorded SEPs consisted of an early positive complex, beginning 8-10 msec after airpuff onset, with two prominent positive peaks (P15 and P25), succeeded by a large negative potential (N43) lasting 30 msec, and a late slow positivity (P70). SEPs, while consistent in wave form, varied slightly between monkeys. The amplitude of the early positive complex was enhanced by increasing the number of stimulated points, or by placing the airpuffs in the receptive fields of cortical neurons located beneath the SEP recording electrode. SEP amplitude was depressed when preceded 20-40 msec earlier by a conditioning stimulus to the same skin area. Single unit responses in areas 3b and 1 of primary somatosensory (SI) cortex consisted of a burst of impulses, beginning 11-12 msec after the airpuff onset, and lasting another 15-20 msec. Peak unitary activity occurred at 12-15 msec, corresponding to the P15 wave in the SEP. No peak in SI unit responses occurred in conjunction with the P25 wave. Although SI neurons fired at lower rates during P25, the lack of any peak in SI unit responses suggests that activity in other cortical areas, such as SII cortex, contributes to this wave. Most unit activity in SI cortex ceased by the onset of N43, and was replaced by a period of profound response depression, in which unit responses to additional tactile stimuli were reduced. We propose that the N43 wave reflects IPSPs in cortical neurons previously depolarized and excited by the airpuff stimulus. Late positive potentials (P70) in the SEP had no apparent counterpart in SI unit activity, suggesting generation at other cortical loci.

Animals↗

Abnormalities of thyroid function in infants with Down syndrome.

We describe 12 of 1130 infants with Down syndrome in whom various degrees of thyroid dysfunction were detected by neonatal screening. These aberrations were confirmed subsequently in 11 patients. In eight of 11 children, persistent primary hypothyroidism, was diagnosed, whereas in the remaining three patients transient thyroid abnormalities were noted. The twelfth patient died and could not be retested. We found an incidence of persistent primary congenital hypothyroidism in infants with Down syndrome of 1:141, or about 28 times more than in the general population. The cause of thyroid aberrations in these infants remains unclear; none of the studied patients had agenesis or ectopia of the thyroid gland. On initial screening most infants with Down syndrome had only mild biochemical abnormalities, with gradual decompensation occurring thereafter. Infants with Down syndrome are therefore at high risk for congenital hypothyroidism and should have careful follow-up to prevent further deterioration of their mental development or growth.

Child, Preschool↗

Novel method for studying the public health significance of macroinvertebrates occurring in potable water.

An experimental procedure was developed to study the association of selected bacteria and macroinvertebrates and their response to free available chlorine disinfection. The organisms selected for study were Escherichia coli ( LacZ545 ), Enterobacter cloacae (ATCC 23355), and the amphipod Hyalella azteca . E. coli was shown to bind tightly (1.6 X 10(4) CFU per amphipod ) to this macroinvertebrate and to resist repeated attempts to wash it off. E. cloacae was shown to bind much less tightly (1.4 X 10(3) CFU per amphipod ) to H. azteca and was less resistant to removal by washing. The extent of association is a function of macroinvertebrate size (surface area), but the procedure produces repeatable results usable for controlled experimentation. This method, together with the dual bacterial identification criteria (morphology and antibiotic resistance), was used to study the response of unassociated and associated E. coli and E. cloacae to disinfection with free available chlorine at 1.0 mg/liter. Unassociated E. coli populations decreased to less than 1% of their zero time controls within 1 min of contact time, whereas more than 2% of the associated E. coli populations remained viable after 60 min of contact at 1.0 mg of free available chlorine per liter. Unassociated E. cloacae populations decreased to less than 1% of their zero time controls within 1 min of contact time, whereas ca. 15% of the associated E. cloacae populations remained viable after 60 min of contact at 1.0 mg of free available chlorine per liter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗

Non-invasive measurement of cardiac output by a single breath constant expiratory technique.

A new single breath test has been developed that measures pulmonary blood flow (Qc) and pulmonary tissue volume by using the fact that Qc is proportional to the relationship between the absorption rate of acetylene (C2H2) from the alveolar gas and the rate of change of lung volume during constant expiratory flow. To make these measurements a bag in bottle system with a rolling seal spirometer, a mass spectrometer, and a minicomputer with analogue to digital conversion have been used. Qc was compared with cardiac output measured by the thermodilution technique in 20 patients with cardiac disease; some also had mild chronic obstructive pulmonary disease. The mean (SD) resting Qc for the group was 5.27 (1.22) l/min and the cardiac output measured by thermodilution was 5.30 (1.31) l/min. The mean difference between the two estimations of cardiac output was 0.03 l and the standard deviation of this difference was 0.76 l. The Qc technique was not successful in patients with an FEV1/FVC less than 60%, but seemed to be accurate in those with higher FEV1/FVC values. Correction of Qc for the effect of venous admixture in 14 patients resulted in an average 19% overestimation of cardiac output (6.01 (2.52) l/min v 5.05 (1.64) l/min). It is concluded that cardiac output can be accurately measured in patients with cardiac or mild pulmonary disease. No correction for venous admixture due to ventilation-perfusion mismatch was necessary in these patients, presumably because the large breath used by the technique overcomes most mild ventilation-perfusion maldistribution. These findings, in addition to the non-invasive nature of the technique, suggest potential value for the measurement of cardiac output in various clinical conditions.

Adult↗

Discharged state hospital patients' characteristics and use of aftercare: effect on community tenure.

A study of a publicly funded mental health system determined that the use of aftercare services by discharged patients had the effect of extending community tenure. Patients' clinical characteristics, particularly number of previous hospitalizations, had only minimal effect and patients' demographic characteristics had essentially no impact on community tenure. Increasing the variety and intensity of rehabilitation-oriented types of service rather than increasing the frequency of supportive contacts through individual therapy and case management appears to hold the greatest promise for extending community tenure.

Adolescent↗

Family therapy with the elderly mentally ill. Some strategies and techniques.

Over a six month period, 142 consecutive referrals of patients over 65 to a community-orientated psycho-geriatric service in North London were studied. The psycho-social factors determining referral were quantified and their relationship to diagnosis analysed. Therapeutic strategies are described, devised to deal with the presenting psycho-social problems. It is suggested that a family-centred approach is of some value in the management of the elderly mentally ill.

Aged↗

State dependence of noradrenergic activity in a rapidly cycling bipolar patient.

Plasma levels of the major norepinephrine (NE) metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were measured in a rapidly cycling bipolar patient and her first-degree relatives. The mood state dependence and the reciprocal relationship between noradrenergic and cholinergic activity were investigated by assessing mood, thought disorder, and plasma MHPG following the infusion of physostigmine. A correlation was found between plasma MHPG and mood states, with exceedingly high levels during mania and hypomania. Levels were significantly decreased by ECT or combined lithium and chlorpromazine administration. A pathologic diurnal MHPG pattern was detected during periods of abnormal mood changes. Infusion of physostigmine led to a prompt reduction in MHPG release and a marked decline in mood-state measurements and the overall level of thought disorder. Muscarinic receptors exerting negative feedback control over the synthesis and/or release of NE may have become supersensitive as a consequence of alpha 2-adrenoceptor densensitization.

Adolescent↗

Brain spectrin. Isolation of subunits and formation of hybrids with erythrocyte spectrin subunits.

Brain spectrin tetramer was purified from pig brain membranes in milligram quantities. The tetramer had subunits of Mr = 265,000 (alpha) and Mr = 260,000 (beta), Rs = 21.4 nM, S20,w = 11 S, V = 0.725 ml/g, frictional ratio of 2.9, and calculated molecular weight of 9.7 x 10(5). The subunits were isolated in greater than 95% purity by chromatography on hydroxylapatite in 7 M urea, as described for erythrocyte spectrin (Calvert, R., Bennett, P., Gratzer, W. (1980) Eur. J. Biochem. 107, 355-361). Peptide maps of the subunits revealed few if any common peptides. The subunits were visualized by rotary shadowing as single-stranded flexible rods 100 nm in length with no homodimers by lateral or end association. When the subunits were renatured together, double-stranded tetramers 200 nm in length were formed, as well as higher oligomers. These results indicate that spectrin tetramers are formed by laterally associated alpha,beta dimers attached by head-to-head linkage of each alpha chain with a beta chain. The reassembled subunits regained the ability to increase the low shear viscosity of actin, although isolated alpha or beta subunits were inactive. Hybrid molecules were formed with brain alpha and pig erythrocyte spectrin beta subunit and were visualized as double-stranded rods 100 nm long with no tetramers. 125I-labeled brain alpha chain that was hybridized with erythrocyte beta subunit acquired the ability to bind to ankyrin sites on erythrocyte membranes. 125I-labeled brain alpha chain bound only to beta subunits of erythrocyte and brain spectrin following transfer of these polypeptides to nitrocellulose paper from sodium dodecyl sulfate gels. Affinity-purified antibodies against brain spectrin cross-reacted with both subunits of erythrocyte spectrin and with polypeptides of a similar molecular weight to brain spectrin in membranes of all tissues examined. Cross-reacting polypeptides were localized exclusively in plasma membranes of subcellular fractions from liver. These studies provide strong additional evidence that brain and mammalian erythrocyte spectrin belong to a closely related family of proteins with conserved functions in both subunits.

Actins↗

Spectrin and ankyrin in brain.

Further similarity between mammalian erythrocyte spectrin and pig brain spectrin has been demonstrated by (a) formation of hybrid molecules with brain alpha-chains and erythrocyte beta-chains and by (b) identification of an ankyrin protein in brain membranes. Hybrid spectrin molecules prepared from brain alpha-chains and erythrocyte beta-chains were visualized by low-angle rotary shadowing as double-stranded rods (dimers) 100 nM in length. 125I-labeled brain alpha-chain that was hybridized with erythrocyte beta-subunit acquired ability to bind to ankyrin sites on erythrocyte membranes. 125I-labeled brain alpha-chain bound only to beta-subunits of erythrocyte and brain spectrin following transfer of these polypeptides to nitrocellulose paper from sodium dodecyl sulfate (SDS) gels. Thus brain spectrin and mammalian erythrocyte spectrin have shared functional sites involved in association of their subunits. Additional evidence for similarity of brain and erythrocyte membranes is the finding of a 210,000 Mr membrane protein in brain that cross-reacts with erythrocyte ankyrin and has a water-soluble domain of 72,000 Mr that is produced by protease digestion. The 72,000 Mr domain of brain ankyrin has been isolated by affinity chromatography on erythrocyte spectrin-Sepharose, and was demonstrated to bind directly to erythrocyte and brain spectrin. The brain 72,000 Mr fragment has distinct peptide maps from the erythrocyte 72,000 Mr ankyrin fragment and thus is not a result of erythrocyte contamination.

Animals↗