Biomedical subjects
Publications and source records attributed to J Rogers.
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Delta-9-tetrahydrocannabinol (THC), a substance in marihuana, was found to produce a profound potentiation of reserpine-induced hypokinesia in rats as measured with a bar test. In these experiments, THC had no hypokinetic effect by itself but produced a more than 20-fold increase in the hypokinesia produced by reserpine. Reserpine-induced hypokinesia has been viewed as animal model of Parkinson's Disease. THC potentiation of reserpine-induced hypokinesia was observed to be both time- and dose-dependent (1 to 10 mg/kg THC). When administered by gavage to reserpine-pretreated subjects (7.5 mg/kg IP, 24 hours before), THC produced a potentiation of hypokinesia that developed fully within 1 hour, lasted at least 5 hours, and was absent by 12 hours after THC administration. This THC effect was slightly increased by physostigmine, a cholinesterase inhibitor, relatively unaffected by scopolamine, a muscarinic antagonist, and almost completely blocked by ethopropazine, an anticholinergic antiparkinson drug. The effect was completely unaffected by naloxone. Insofar as reserpine has been used with some clinical efficacy in hyperkinetic movement disorders such as Huntington's disease and tardive dyskinesia, it may be that potentiation of reserpine's hypokinetic effect by a drug such as THC could greatly increase the clinical value of reserpine or related drugs in the treatment of these disorders.
In cell lines producing IgM, secreted and membrane bound forms of immunoglobulin mu heavy chains are produced from two separate mu mRNAs that are identical except for alternative 3' coding sequences. We now show that cell lines producing IgG likewise contain two mRNA species for immunoglobulin gamma chains. The major, 1.7 kilobase (kb) species encodes secreted gamma chains. A less abundant species of 3-4 appears to encode membrane bound gamma chains, in that it contains an alternative 3' end encoded in separate exons 3' to the remainder of the gene. The first exon of this M gene segment has been identified in chromosomal gamma 1 and gamma 2b gene clones by its sequence homology with the corresponding exon in the mu gene. Like the mu M exon, it encodes a probable transmembrane polypeptide segment. The flanking DNA sequences show a patchwork pattern of homology between genes that suggests a checkered evolutionary history.
Two groups of naive male Sprague-Dawley rats, 5-7 and 24-26 months of age, were anesthetized with continuous intraperitoneal infusion of 4% chloral hydrate. Stimulation of the cerebellar vermis molecular layer permitted measurements of 12 different electrophysiological properties of parallel fiber Purkinje cell circuitry: parallel fiber conduction velocity, refractory period, threshold, and current dependent volley amplitude; slow negative wave threshold and current dependent amplitude; Purkinje cell activation threshold, latency, and current dependent spike driving; and Purkinje cell inhibitory threshold, latency, and current dependent duration of inhibition. Old subjects demonstrated deficits on all parameters except Purkinje cell inhibitory threshold. The relevance of these findings to our previous research on senescent changes in cell number, lipofuscin deposition, and spontaneous firing of Purkinje cells is discussed.
The methylation of immunoglobulin heavy chain genes was examined before and after class switching, by using the Hpa II/Msp I restriction mapping technique. The mu, delta, and gamma 1 genes all are methylated in cells that do not express them but are demethylated when they are expressed. In particular, the delta gene remains methylated, and thus presumably untranscribed, in a cell line that probably represents an early stage of B-cell differentiation and produces only mu heavy chains. Because mu and delta RNAs are cotranscribed from a single complex transcription unit at a later stage of B-cell differentiation, this finding implies that the mu-plus-delta complex transcription unit is of variable length.
From a library of mouse sperm DNA, we have isolated two overlapping clones which contain the C(delta) gene. One of these clones also contains the C(mu) gene. The C(delta) gene is separated from the C(mu) membrane exons by approximately 2 kilobases (kb) of DAN. The C(delta) gene was identified by (a) hybridization to poly(A)(+)RNA prepared from the IgD-producing rat plasma cell tumor IR731, and (b) homology of a translated nucleotide sequence to the amino acid sequence of the human delta chain. The C(delta) gene spans 8 kb of DNA in the germ line. Plasmid subclones of the C(delta) gene were used as probes in Southern and RNA blot experiments. RNA blot analysis of cytoplasmic poly(A)(+)RNA from IR731 and a mu(+)delta(+) B-cell hybridoma revealed 1.6- and 2.7-kb delta mRNA species with different 3' ends, which presumably encode the secreted and membrane-bound forms, respectively, of the delta chain. Southern blot analysis of DNA from two mu(+)delta(+) lymphomas revealed that the C(delta) gene is in the germ-line configuration in each case. Restriction map analysis of C(mu) and C(delta) genomic clones isolated from a library of normal mu(+)delta(+) B-cell DNA also gave no evidence for DNA rearrangement in the region between the C(mu) and C(delta) genes. Taken together, these data suggest that IgD expression in mu(+)delta(+) B cells does not involve a V(H)-to-C(delta) DNA switch rearrangement. We propose that simultaneous expression of C(delta) and C(delta) with a single V(H) gene is mediated by two alternative routes of RNA processing of a primary nuclear transcript which contains the V(H), C(mu), and C(delta) genes. In contrast, analogous experiments with myeloma IR731 DNA revealed that the C(mu) gene has been deleted from the myeloma DNA and that the C(delta) gene has undergone DNA rearrangement, presumably including a switch recombination of the V(H) gene from the C(mu) to the C(delta) gene. These results indicate that two alternative mechanisms may be used in the expression of IgD molecules-RNA splicing in B cells and DNA rearrangement in plasma cells.
A multiple regression analysis was used to investigate the explanatory potential of a multidimensional approach to risk of psychological impairment. Information from a study of bereavement in Canadian women included meaning of the event to the individual, personality attributes, social supports available following bereavement and sociodemographic data. Risk of psychological impairment was estimated by score on the General Health Questionnaire (GHQ). Sixty-four per cent of the variance in GHQ scores at one month postbereavement was accounted for. The authors hypothesize that the addition of a measure of coping styles and more comprehensive measures of the other dimensions studied would increase the power of the technique. It seems critical to take into account the possible large effects of sociodemographic factors.
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Although tetraploidy of human chromosomes (92,XXYY) has been described frequently in abortuses, only one example in a liveborn infant has previously been described. A second malformed infant with a complete tetraploid chromosome complement, who lived for 15 days, is reported. In addition to many of the malformations described in the first case, this infant also had a sacral myelomeningocele and skeletal anomalies. The probable origin of the tetraploidy was a failure of cytoplasmic cleavage at the first mitotic division of the fertilised ovum.
The reproductive performance of 106 patients exposed in utero to diethylstilbestrol by maternal ingestion is described. Fetal wastage is high, apparently because of spontaneous abortion during the first and second trimesters. Recommendations are made for preconception counseling of exposed progeny to increase fetal salvage.
Childhood poisoning is a leading cause of death in children one to four years of age. This report reviews the recent literature regarding the causes of accidental poisonings and explores the potential for prevention through family centered behavioral intervention. Attributes of the host, agent, and environment related to single and repeat poisoning are highlighted. The children are usually under five years of age and exhibit distinguishing behavioral characteristics. Substances ingested include prescribed and over-the-counter medications or common household substances. Types of poisons, toxicity, and availability do not differ in homes of ingestors and noningestors. However, more major stresses in the family have been identified for ingestors than noningestors. A treatment approach based on social learning theory is proposed.
Alcoholism is a major health problem in the United States, yet it has not received high priority in medical education. Although it affects many patients who attend the offices of family physicians, it frequently remains unrecognized. It is therefore an appropriate topic for a family medicine course and has been integrated into a third year clerkship at the University of Washington. Students are taught basic diagnostic and management skills by sensitizing them to the magnitude of the problem and addressing some professional attitudinal blocks. history taking skills emphasizing early recognition and intervention are stressed, and the role of community resources in treatment is demonstrated through discussion and site visits.
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After single injections of ethanol (1-4 g/kg, i.p.), single unit extracellular recordings of rat cerebellar Purkinje cells show dramatically increased frequency of climbing fiber bursts and occasional increases in simple spike firing rate. These effects of ethanol are not observed in rats chronically treated with the substance for 11-14 days: firing patterns 0-3 h after the last ethanol administration do not differ significantly from controls. However, rats chronically treated and then withdrawn from ethanol slow significant, progressive decreases in climbing fiber activity and firing rates from 3 to 32 h after the last ethanol administration. These effects on cerebellar Purkinje cell firing appear to be physiological correlates of the phenomena of ethanol intoxication, tolerance, and dependence.
The IgM molecule is composed of subunits made up of two light chain and two heavy chain (mu) polypeptides. The mu chain is encoded by several gene segments--variable (V), joining (J) and constant (Cmu). The Cmu gene segment is of particular interest for several reasons. First, the mu chain must exist in two very different environments--as an integral membrane protein in receptor IgM molecules (micrometer) and as soluble serum protein in IgM molecules into the blood (mus). Second, the Cmu region in mus is composed of four homology units or domains (Cmu1, Cmu2, Cmu3 and Cmu4) of approximately 110 amino acid residues plus a C-terminal tail of 19 residues. We asked two questions concerning the organisation of the Cmu gene segment. (1) Are the homology units separated by intervening DNA sequences as has been reported for alpha (ref. 5), gamma 1 (ref. 6) and gamma 2b (ref. 7) heavy chain genes? (2) Is the C-terminal tail separated from the Cmu4 domain by an intervening DNA sequence? If so, DNA rearrangements or RNA splicing could generate hydrophilic and hydrophobic C-terminal tails for the mus and micrometer polypeptides, respectively. We demonstrate here that intervening DNA sequences separate each of the four coding regions for Cmu domains, and that the coding regions for the Cmu4 domains and the C-terminal tail are directly contiguous.
The effects of amphetamine and pentobarbital upon electrographic state were studied in naive cats and cats with forebrain lesions that induce insomnia. Amphetamine increased alertness and decreased both slow wave sleep (SWS) and rapid eye movement (REM) sleep states for up to 12 h in both intact animals and cats with lesions. Pentobarbital inhibited REM sleep and alert states while increasing SWS and drowsy states in naive cats. The effect was mainly restricted to the first 8 h. In cats with forebrain lesions, the effects were similar except that the amount of REM sleep was significantly elevated. During a portion of the first 8 h, the tracing cannot be distinguished from a normal control sample. It is hypothesized that pentobarbital mimics the normal inhibitory influence of the intact forebrain and either induces or facilitates 'normal' sleep patterns in cats with forebrain lesions.