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Biomedical subjects

D Barker

Publications and source records attributed to D Barker.

At least 127 records · Page 7Linked to original sources

A test of the role of two oncogenes in inherited predisposition to colon cancer.

Inheritance of mutationally altered oncogenes could predispose individuals to the development of specific tumors and account for familial tumor phenotypes. Using adjacent DNA sequence polymorphisms as genetic markers, we have examined two oncogenes, the Kirsten ras2, isolated from a human colon cancer cell line, and the Harvey ras1, isolated from a human bladder cancer cell line, for their role in the genetic etiology of inherited colon cancer in Gardner syndrome. Both oncogene loci have been shown to be unlinked to the Gardner syndrome locus and are, therefore, eliminated as candidates for the Gardner syndrome gene.

Base Sequence↗

Single-copy sequence hybridizes to polymorphic and homologous loci on human X and Y chromosomes.

Use of a 4.5-kilobase-pair (kb) segment of single-copy DNA from a human genomic library as a hybridization probe of genomic human DNAs revealed allelic Taq I restriction fragments 10.6, 11.8, and 14.6 kb long. Among 12 unrelated individuals, all 6 males exhibited the 14.6-kb fragment in addition to one of the other fragments. Three of the females displayed 10.6- and 11.8-kb fragments, and the other three displayed only one fragment length; none had the 14.6-kb fragment. Hybridization of this probe to Taq I-digested DNAs from human-rodent hybrid cell lines (which have partial complements of human chromosomes) demonstrated segregation of the 14.6-kb fragment with the human Y chromosome and segregation of the 10.6- and 11.8-kb fragments with the human X chromosome. Furthermore, hybridization of this probe to Taq I-digested DNAs from 48 members of a single kindred revealed Y-linked inheritance of the 14.6-kb fragment and X-linked inheritance of the 10.6- and 11.8-kb fragments. These experiments demonstrate homology between single-copy sequences on the human X and Y chromosomes.

Alleles↗

Autonomic innervation of receptors and muscle fibres in cat skeletal muscle.

Cat hindlimb muscles, deprived of their somatic innervation, have been examined with fluorescence and electron microscopy and in teased, silver preparations; normal diaphragm muscles have been examined with electron microscopy only. An autonomic innervation was found to be supplied to both intra- and extrafusal muscle fibres. It is not present in all muscle spindles and is not supplied at all to tendon organs. Fluorescence microscopy revealed a noradrenergic innervation distributed to extrafusal muscle fibres and some spindles. On the basis of the vesicle content of varicosities the extrafusal innervation was identified as noradrenergic (32 axons traced), and the spindle innervation as involving noradrenergic, cholinergic and non-adrenergic axons (14 traced). Some of the noradrenergic axons that innervate spindles and extrafusal muscle fibres are branches of axons that also innervate blood vessels. We cannot say whether there are any noradrenergic axons that are exclusively distributed to intra- or extrafusal muscle fibres. The varicosities themselves may be in neuroeffective association with striated muscle fibres only, or with both striated fibres and the smooth muscle cells in the walls of blood vessels. The functional implications of this direct autonomic innervation of muscle spindles and skeletal muscle fibres are discussed and past work on the subject is evaluated.

Animals↗

Identifications of the intrafusal endings of skeletofusimotor axons in the cat.

Direct identification of the endings of skeletofusimotor (beta) axons has been made in muscle spindles deprived for their gamma innervation by degeneration. Hindlimb muscles were prepared in which 1--5 fast-conducting motor axons were left intact while the rest of the motor supply was cut and allowed to degenerate for a period of 7 days. In 3 experiments a single beta axons survived supplying tenuissimus, and in 2 experiments beta axons were among 4 or 5 surviving axons that supplied superficial lumbrical and abductor digiti quinti medius muscles. Motor endings identified as p1 plates were found in teased, silver preparations of all experimental muscles, a total of 35 such plates being located in 15 spindles. The plates were all supplied to bag1 fibres. The experiments show that if a spindle innervated by a beta axon is deprived of its gamma supply by degeneration the motor endings that remain intact are p1 plates.

Animals↗

Joint nursing-pharmacy program helps reduce medication errors.

A hospital's nursing and pharmacy staffs have substantially reduced errors in medication administration, especially errors of omission. They have achieved the reductions partly through primary nursing, which demands greater accountability for total patient care, including medication, from each nurse. Other methods and aids include corrective action, special reports and audits, "remainder" cards, and a computer system.

California↗

Identification of intrafusal muscle fibres activated by single fusimotor axons and injected with fluorescent dye in cat tenuissimus spindles.

1. Intrafusal muscle fibres of cat tenuissimus spindles have been injected with the fluorescent dye Procion Yellow and identified histologically after recording their changes in membrane potential during 1/sec stimulation of single static or dynamic gamma axons. 2. Thirteen intrafusal muscle fibres innervated by static gamma axons were identified as eight bag2 and five chain fibres. The fact that none proved to be a bag1 fibre is not regarded as significant, for reasons given in the Discussion. 3. In one spindle Procion Yellow was injected into two intrafusal muscle fibres activated by the same static gamma axon; they were identified as a bag2 and a chain fibre. 4. Nine intrafusal muscle fibres innervated by dynamic gamma axons were identified as seven bag1 fibres, one bag2 fibre, and one long chain fibre. 5. In one spindle two bag fibres were injected, one activated by a dynamic gamma axon, the other by a static gamma axon; the former proved to be a bag1 fibre, the latter a bag2 fibre. 6. Stimulation of static gamma axons elicited junctional potentials in seven bag2 fibres and one damaged chain fibre, and action potentials in one bag2 and four chain fibres. In the whole sample of impaled intrafusal muscle fibres (identified and unidentified) activated by static axons, junctional potentials were recorded from twenty-three (62.2%), and action potentials from fourteen (37.8%). Stimulation of dynamic gamma axons always elicited junctional potentials. 7. In a number of instances it was possible to examine the ultrastructure of motor endings belonging to the stimulated gamma axon. The myoneural junctions of trail endings supplied by static gamma axons to bag2 and chain fibres were both smooth and folded; the deepest and most regular folding occurred on chain fibres. The terminals of p2 plates supplied to bag1 fibres by dynamic gamma axons had smooth myoneural junctions.

Action Potentials↗

Histological analysis of cat muscle spindles following direct observation of the effects of stimulating dynamic and static motor axons.

1. Eleven cat tenuissimus spindles have been analysed mainly by cutting serial, transverse, 1 micrometer thick sections following direct observation of the effects of dynamic motor (gamma or beta) stimulation. 2. Histological results from these spindles were also used to interpret the effects of static fusimotor stimulation of other spindles. 3. Dynamic motor stimulation usually produced contractions seen as convergent movements of sarcomeres in single bag fibres, identified as bag1 fibres for reasons given in the text. 4. In one spindle a single dynamic axon produced a translational movement in one pole of a bag1 fibre and a convergent movement in each pole of a bag2 fibre, together with movements in other unidentified (presumably chain) fibres. Subsequent analysis showed that besides innervating both bag fibres the axon also supplied two chain fibres. 5. Contrary to expectation, motor endings on the bag1 fibres seldom occurred at the sites of convergent movement. Only two cases of coincidence occurred among sixteen foci and twenty-one motor endings; otherwise focus and nearest ending were separated by distances of 0.85--2.5 mm. 6. Most of the convergent movements of sarcomeres observed in bag1 fibres occurred in a region of the pole that is ultrastructurally distinct from the region where most of the motor endings were located. The possible relevance of this to the production of contractions in the bag1 fibre is discussed. 7. Convergent movement foci in bag2 fibres produced by the stimulation of static axons occurred largely within the same regions of the pole as the motor endings were located, though, whereas foci were observed in both intra- and extracapsular regions, most of the endings were intracapsular.

Animals↗