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Biomedical subjects

P Little

Publications and source records attributed to P Little.

At least 19 recordsLinked to original sources

Reciprocal changes in myosin isoform mRNAs of rabbit skeletal muscle in response to the initiation and cessation of chronic electrical stimulation.

Changes in myosin heavy chain (MHC) mRNAs were studied in rabbit fast-twitch muscles during continuous electrical stimulation at 10 Hz for periods up to 3 weeks, and during the first 12 days of the recovery process that followed cessation of 6 weeks' stimulation. Two cDNA probes were used to detect MHC mRNAs specific to fast- and slow-twitch skeletal muscle in RNase protection assays and Northern- and slot-blot analyses. The isolation and base sequence of one of these probes, corresponding to the MHC gene expressed in soleus (slow-twitch), is described. At an early stage of the response to stimulation, fast MHC mRNA was replaced by slow MHC mRNA. During recovery, this process occurred in reverse but took longer. The time course of recovery was slightly faster in tibialis anterior than in extensor digitorum longus. The changes in mRNAs during both stimulation and recovery reflected changes in the corresponding muscle proteins.

Animals

11p15.5-specific libraries for identification of potential gene sequences involved in Beckwith-Wiedemann syndrome and tumorigenesis.

Constitutional and somatic chromosomal abnormalities of the chromosome 11p15 region are involved in an overgrowth malformation syndrome, the Beckwith-Wiedemann syndrome (BWS), and in several types of associated tumors. The bias in parental origin for the different etiologic forms of this syndrome and for loss of heterozygosity in the tumors suggests that a gene (or genes) mapping to this region undergoes genomic imprinting. However, the precise localization of the locus (or loci) for the BWS and associated tumors is still unknown and more markers are required. We therefore isolated 11p15 markers from two libraries: the first one obtained by microdissection of the chromosome 11p15.5 region and the second one, a phage library, constructed from a hybrid cell line containing this region as its sole human DNA. Of 19 microclones isolated from the microdissection library, 11 were evolutionarily conserved. Four phage clones were isolated; one (D11S774) detected a highly informative variable number of tandem repeats (VNTR) and another (D11S773) a biallelic polymorphism. These clones were sublocalized using a panel of somatic cell hybrids that defines eight physical intervals in 11p15.5. Twenty-one clones map to the distal interval that harbors the BWS locus.

Animals

Reciprocal changes in myosin isoform expression in rabbit fast skeletal muscle resulting from the application and removal of chronic electrical stimulation.

Chronic indirect electrical stimulation of adult mammalian skeletal muscle brings about a transformation from the fast-twitch to the slow-twitch type. Underlying this transformation there is a sequence of profound changes in the expression of proteins involved in all the major molecular systems of the muscle. These include qualitative changes in the expression of myosin light and heavy chain isoforms. The time course of these changes has been studied in some detail at the protein level, both during chronic stimulation and during the recovery process that follows the cessation of stimulation. Here we report on the use of cDNA probes to study corresponding changes in myosin heavy chain (MHC) and light chain (MLC) mRNAs in rabbit fast-twitch muscles during continuous electrical stimulation at 10 Hz and during the first 12 days of recovery after cessation of 6 weeks of stimulation. At an early stage of the response to stimulation, fast MHC mRNA is replaced by slow MHC mRNA. During recovery this process occurs in reverse but takes longer. Broadly similar changes are seen for MLC mRNAs, although the time course is somewhat different. These experiments contribute to a growing body of evidence that many of the protein changes induced by chronic stimulation are the result of regulatory events that take place at a pre-translational level.

Animals

Multiple growth abnormalities in vascular smooth muscle from spontaneously hypertensive rats.

1. In tissue culture the growth characteristics of aortic smooth muscle cells isolated from spontaneously hypertensive rats (SHR) were compared with those of normotensive Wistar-Kyoto (WKY) rats. 2. Aortic smooth muscle cells from SHR exhibit enhanced proliferation when grown in the presence of low (1%) and moderate (5%) concentrations of fetal calf serum. 3. Cell quiescence in cultures of smooth muscle from SHR becomes apparent at cell densities approximately 20% higher than in cultures from WKY rats. 4. These different growth characteristics of smooth muscle between the two strains of rats may contribute to the early pre-hypertensive development of vascular hypertrophy in the SHR.

Animals

Primary "brown pigment" bile duct stones.

Bile duct stones from 42 patients were morphologically and chemically analysed. The calculi from 27 patients had important primary bile duct stone (PBDS) features, consisting of a general ovoid shape and fragile structure, with alternating light and dark brown pigmented layers on cross-section. Chemically these stones contained low levels of cholesterol, with high levels of bilirubin and calcium. Subsequent infrared spectroscopy analysis showed that calcium bilirubinate and calcium palmitate were the only calcium salts present. Calcium palmitate was prominent in the light brown layers. A morphological and chemical comparison with gallbladder stones showed that bile duct "stasis stones" were similar in morphological and chemical composition to the brown pigment gallbladder calculi. However, they were distinct from most gallbladder stones, indicating that primary bile duct calculi have an aetiology that is different to 90% of gallbladder calculi. Primary bile duct calculi were observed to occur with or without the presence of a gallbladder, and more interestingly, in the bile duct of two patients with cholesterol gallbladder stones. Bile duct bile of patients with primary choledocholithiasis were always moderately to profusely infected and with abundant calcium bilirubinate precipitation. Moreover, this study has shown that PBDS chemical analyses profiles were consistent and correlated well with their defined morphology. Consequently, PBDS may be accurately identified at the time of operation by morphology. An important aetiological factor would appear to be infection, which would seem to promote bile duct bile stasis and eventual stone growth.

Bile Duct Diseases

A controlled trial of a low sodium, low fat, high fibre diet in treated hypertensive patients: effect on antihypertensive drug requirement in clinical practice.

The effect of a low sodium, low fat, high fibre diet in allowing a reduction of antihypertensive medication was compared with the effect produced by the individual components of this diet in an observer-blind controlled trial using 196 patients with essential hypertension. Patients were followed up 1.5 months after the last change in medication. In the control group a 33% reduction in medication was possible, with 24% of patients off medication altogether. The low fat, high fibre and low sodium groups showed larger reductions in medication (38%, 47% and 45% respectively), but not significant compared with the control group. The combination group had the largest and highly significant medication reduction (64%), and significantly more patients stopped medication (57.5%), compared with the control group. Since compliance assessment closely corresponded to normal clinical practice these results should represent what is possible in routine clinical practice. This is of importance as drug treatment has side effects, and may be associated with increased cardiovascular risk not found with dietary alternatives.

Antihypertensive Agents

Regional localization of polymorphic markers on chromosome 10 by physical and genetic mapping.

The human vimentin gene and a random DNA segment (D10S39) were mapped to the short arm of human chromosome 10 by linkage analysis. A panel of somatic cell hybrids and monosomy cell-lines, which divide chromosome 10 into seven regions, was used to localize 10 polymorphic markers on this chromosome. The physical map locations obtained correlate well with linkage maps of chromosome 10. Two markers which have been shown to be closely linked to the gene for multiple endocrine neoplasia type 2A map distal to a translocation breakpoint in band 10q11.2.

Animals