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Biomedical subjects

D Barker

Publications and source records attributed to D Barker.

At least 19 recordsLinked to original sources
PubMed1992

Charcot-Marie-Tooth neuropathy type 1A mutation: apparent crossovers with D17S122 are due to a duplication.

A locus for the slow conducting form of Charcot-Marie-Tooth neuropathy (CMT1A) was localised to the proximal short arm of chromosome 17, in band p11.2, distal to D17S58. Linkage studies of CMT1A in 3 large Australian families with the marker loci D17S58, D17S71, and D17S57 suggested the order, pter-CMT1A-D17S71-D17S58-centromere-D17S57. However, the estimate of the recombination fraction between CMT1A and D17S122, also assigned to p11.2, was incompatible with known map distances. The impasse was resolved when the D17S122 genotypes were revised to take into account a dosage effect due to a duplication. After correction of the genotypes, the maximum lod score between CMT1A and D17S122 increased from 0.53 at a recombination fraction of 0.3 to 34.28 at zero recombination. This result emphasizes that genotypes for markers in the p12-p11.2 region should be examined very carefully as ignoring the duplication changes the linkage results dramatically. The fact that no crossovers were found between CMT1A and D17S122 suggests that the duplication may cause the disease phenotype.

Charcot-Marie-Tooth Disease↗
PubMed1992

A study of glycogen depletion and the fibre-type composition of cat skeleto-fusimotor units.

1. We have used the glycogen-depletion technique, combined with myofibrillar ATPase (mATPase) staining for muscle fibre type, to study the fibre-type composition of four skeleto-fusimotor (beta) units in cat peroneus tertius, namely, one beta dynamic (beta d) unit and three beta static (beta s) units. 2. Depletion of glycogen was observed in serial cross-sections of thirty-four beta-unit extrafusal muscle fibres of various types traced from origin to insertion. No fibre was depleted of glycogen throughout its length; depletion was restricted to a number of zones, usually about five. Oxidative (type I) and oxidative-glycolytic (type IIA) fibres were depleted for a significantly greater proportion of their total length than glycolytic IIB fibres. 3. The fibre-type composition of the beta d unit was determined by tracing its fibres from end to end. The muscle unit consisted of one intrafusal bag1 fibre and ninety-three extrafusal muscle fibres comprising seventy-six type I fibres, eleven IIC fibres, and six fibres that changed from IIC to I during the course of their length (IIC/I fibres). The extrafusal fibre-type composition was thus 81.7% I plus 18.3% IIC and IIC/I. 4. The three beta s units (beta s1, beta s2, beta s3) were all fast-contracting and fatigued rapidly. Identification of their extrafusal fibre types, made in 1 mm2 areas sampled from different parts of each unit, gave mixed compositions as follows: beta s1, IIB + 6.7% IIA; beta s2, IIB + 5.8% IIA; beta s3, IIB + 29.9% IIA. The intrafusal component of each unit included either one or two long chain fibres. 5. In a discussion of the results, the fact that the continuous stimulation of extrafusal muscle fibres does not deplete them of glycogen throughout their length is examined in relation to the work of others who have assumed that it did. With regard to the finding of mixed extrafusal fibre types in the beta units, a distinction is drawn between minimal (around 5%) and moderate mixing. It is suggested that minimal mixing may occur in any motor unit as the outcome of endplate degeneration with foreign replacement, but that moderate mixing indicates an on-going process of conversion from one fibre type to another which in the adult may prove to occur only among beta units.

Animals↗
PubMed1992

An X-linked human collagen transgene escapes X inactivation in a subset of cells.

Transgenic mice carrying one complete copy of the human alpha 1(I) collagen gene on the X chromosome (HucII mice) were used to study the effect of X inactivation on transgene expression. By chromosomal in situ hybridization, the transgene was mapped to the D/E region close to the Xce locus, which is the controlling element. Quantitative RNA analyses indicated that transgene expression in homozygous and heterozygous females was about 125% and 62%, respectively, of the level found in hemizygous males. Also, females with Searle's translocation carrying the transgene on the inactive X chromosome (Xi) expressed about 18% transgene RNA when compared to hemizygous males. These results were consistent with the transgene being subject to but partially escaping from X inactivation. Two lines of evidence indicated that the transgene escaped X inactivation or was reactivated in a small subset of cells rather than being expressed at a lower level from the Xi in all cells, (i) None of nine single cell clones carrying the transgene on the Xi transcribed transgene RNA. In these clones the transgene was highly methylated in contrast to clones carrying the transgene on the Xa. (ii) In situ hybridization to RNA of cultured cells revealed that about 3% of uncloned cells with the transgene on the Xi expressed transgene RNA at a level comparable to that on the Xa. Our results indicate that the autosomal human collagen gene integrated on the mouse X chromosome is susceptible to X inactivation. Inactivation is, however, not complete as a subset of cells carrying the transgene on Xi expresses the transgene at a level comparable to that when carried on Xa.

Animals↗
PubMed1991

Localization of Charcot-Marie-Tooth disease type 1a (CMT1A) to chromosome 17p11.2.

Charcot-Marie-Tooth (CMT) disease type 1a has been previously localized to chromosome 17 using the markers D17S58 and D17S71. In that report we were unable to provide unequivocal localization of the CMT1A gene on either the proximal p or the q arm. Therefore, data from one additional CMT1A family and typing of other probes spanning the pericentromeric region of chromosome 17 (D17S73, D17S58, D17S122, D17S125, D17S124) were analyzed. Multipoint analysis demonstrates convincing evidence (log likelihood difference greater than 5) that the CMT1A gene lies within 17p11.2 and most likely between the flanking markers D17S122 and D17S124.

Charcot-Marie-Tooth Disease↗
PubMed1990

The achondroplasia gene is not linked to the locus for neurofibromatosis 1 on chromosome 17.

We have investigated genetic linkage of von Recklinghausen neurofibromatosis (NF1) and achondroplasia (ACH) using chromosome-17 markers that are known to be linked to NF1. Physical proximity of the two loci was suggested by the report of a patient with mental retardation and the de novo occurrence of both NF1 and ACH. Since the chance of de novo occurrence of these two disorders in one individual is 1 in 600 million, this suggested a chromosomal deletion as a single unifying molecular event and also that the ACH and NF1 loci might be physically close. To test this, we performed linkage analysis on a three-generation family with ACH. We used seven DNA probes that are tightly linked to the NF1 locus, including DNA sequences that are known to flank the NF1 locus on the centromeric and telomeric side. We detected two recombinants between the ACH trait and markers flanking the NF1 locus. In one recombinant, the flanking markers themselves were nonrecombinant. Multi-point linkage analysis excluded the ACH locus from a region surrounding the NF1 locus that spans more than 15 cM (lod score less than -2). Therefore, analysis of this ACH pedigree suggests that the ACH locus is not linked to the NF1 locus on chromosome 17.

Achondroplasia↗
PubMed1990

Glycoprotein C-dependent attachment of herpes simplex virus to susceptible cells leading to productive infection.

Herpes simplex viruses encode several glycoproteins dispensable for infection and replication in cell culture. Evidence is presented that there exist at least two pathways for viral attachment to cells, i.e., one mediated by the dispensable glycoprotein C (gC) and one independent of that glycoprotein. Thus, whereas the polycations neomycin and polylysine inhibit attachment but not entry of already attached herpes simplex virus 1 (HSV-1) into baby hamster kidney (BHK) cell line, they have no effect on HSV-2 attachment to the same cells (N. Langeland, H. Holmsen, G.R. Lilehaug, and L. Haarr, 1987, J. Virol. 61, 3388-3393; N. Langeland, L.J. Moore, H. Holmsen, and L. Haarr, 1988, J. Gen. Virol. 69, 1137-1145). We report that (i) analyses of intertypic HSV-1 X HSV-2 recombinants indicated that the HSV-2 locus which confers ability to infect BHK cells in the presence of neomycin or polylysine comaps with the gene specifying gC but not with or near the genes specifying the other viral glycoproteins (gB, gD, gE, and gG, and gI), (ii) the smallest HSV-2 DNA fragment capable of transferring this function to HSV-1 was a 2880-bp Sa/l fragment encoding the entire gC (UL44 open reading frame) gene, 515 bp of coding sequences from the UL43 open reading frame and 393 bp of coding sequences from the UL45 open reading frame, but analyses of the recombinant virus DNA excluded UL43 and most of the UL45 sequences, and (iii) definitive evidence that HSV-2 gC confers upon HSV the capacity to infect BHK cells in the presence neomycin or polylysine emerged from studies showing that site-specific mutagenesis which inactivated the gene yielded a recombinant whose attachment to BHK cells was blocked by the polycations. We conclude that in BHK cells there exists in addition to the pathway blocked by neomycina and polylysine a pathway which is parallel and HSV-2 gC dependent.

Animals↗
PubMed1990

Regeneration and recovery of cat muscle spindles after devascularization.

1. We have assessed the sensory reinnervation and recovery of regenerated muscle spindles in extensor digitorum longus (EDL) 6, 8 and 13 weeks after the muscle, with its nerve left intact, had been devascularized. Recordings were made from the dorsal roots of the responses of single afferent fibres to ramp-and-hold stretch of the regenerated spindles whose sensory reinnervation was subsequently examined in teased, silver preparations. 2. The spindle population in four normal EDL muscles ranged from 53 to 83 (mean 69); analysis of the afferent innervation of 166 normal b1b2c spindles showed that 23% had primary endings supplied by two Ia afferents. Regenerated spindles were identified as belonging to one of four groups in which afferents establish sensory endings on intrafusal muscle fibres in groups 1-3, but not in group 4. Sensory reinnervation was complete after 6 weeks recovery and similar proportions of group 1-3 spindles occurred after each recovery period, i.e. 58% after 6 weeks, 65% after 8 weeks and 62% after 13 weeks. We estimate that about half the original spindle population was lost owing to persistent ischaemic necrosis; that 30% regenerated and acquired functional afferent connections (group 1-3 spindles); and that the total loss of spindle afferents was over 60%. 3. The conduction velocities of the regenerated spindle afferents were very similar to those of normal EDL spindle afferents. The proportions that responded normally to ramp-and-hold stretch at the end of each recovery period increased from 58% after 6 weeks to 61% after 8 and 88% after 13. Other responsive spindle afferents were either predominantly phasic or only responded to supramaximal stretch. The proportions of these decreased as recovery progressed reducing from 19% after 6 weeks to 9% after 13 weeks in the case of those giving predominantly phasic responses and from 23% after 6 weeks to 3% after 13 weeks in the case of those unresponsive to physiological stretch. 4. The mean peak and held firing rates of regenerated spindle afferents responsive to 10 mms-1 ramp-and-hold stretches were all significantly lower than normal. There was no marked trend towards higher firing rates after longer periods of recovery through, considered separately, the mean peak firing rates of the normally responding afferents did show a distinct improvement. The mean dynamic and velocity indexes were not significantly different from normal. 5. The ratio of Ia:spindle II afferents, as identified by their responses to stretch, was 1:1.22 in the control animals and 1:1.26 in the experimental series.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

Human-mouse interspecies collagen I heterotrimer is functional during embryonic development of Mov13 mutant mouse embryos.

To investigate whether the human pro alpha 1(I) collagen chain could form an in vivo functional interspecies heterotrimer with the mouse pro alpha 2(I) collagen chain, we introduced the human COL1A1 gene into Mov13 mice which have a functional deletion of the endogenous COL1A1 gene. Transgenic mouse strains (HucI and HucII) carrying the human COL1A1 gene were first generated by microinjecting the COL1A1 gene into wild-type mouse embryos. Genetic evidence indicated that the transgene in the HucI strain was closely linked to the endogenous mouse COL1A1 gene and was X linked in the HucII transgenic strain. Northern (RNA) blot and S1 protection analyses showed that the transgene was expressed in the appropriate tissue-specific manner and as efficiently as the endogenous COL1A1 gene. HucII mice were crossed with Mov13 mice to transfer the human transgene into the mutant strain. Whereas homozygous Mov13 embryos die between days 13 and 14 of gestation, the presence of the transgene permitted apparently normal development of the mutant embryos to birth. This indicated that the mouse-human interspecies collagen I heterotrimer was functional in the animal. The rescue was, however, only partial, as all homozygotes died within 36 h after delivery, with signs of internal bleeding. This could have been due to a functional defect in the interspecies hybrid collagen. Extensive analysis failed to reveal any biochemical or morphological abnormalities of the collagen I molecules in Mov13-HucII embryos. This may indicate that there was a subtle functional defect of the interspecies hybrid protein which was not revealed by our analysis or that another gene has been mutated by the retroviral insertion in the Mov13 mutant strain.

Animals↗
PubMed1990

Lernaeocera branchialis: a potential pathogen to cod ranching.

A study was carried out to determine the effect of Lernaeocera branchialis on Atlantic cod infected in the laboratory and in the field and also to ascertain its effect on cod-ranching. Sixty-four percent (308) of 481 cod acquired infections in the laboratory and 33% (159) of the infected fish died over a 4-yr period. About 74% of the deaths occurred within 4 mo of the infection. Monthly samples of cod collected adjacent to a cod-ranching operation showed an initial prevalence of 30% that subsequently decreased in the following 2 mo to 15%. Prevalence of the infection also decreased among the initial field sample of cod that were kept alive, from 30 to 17% during the same 2-mo period and to 9% after 8 mo and was associated with death caused by the parasite. Cod examined at intervals after infection showed evidence of reduced weight gain, lower liver somatic index, liver lipid, and blood values than controls. A field sample taken from the same area during the summer of the following year indicated a prevalence of 12%. This higher than usual prevalence (4-6%) was associated with retention of the intermediate host, Cyclopterus lumpus, that provided an additional source of infective stages. It is likely that increased parasitism could affect the success of the cod-ranching operation in view of the parasite's devastating effects on its hosts.

Animals↗
PubMed1989

Linkage of Charcot-Marie-Tooth neuropathy type 1a to chromosome 17.

Charcot-Marie-Tooth disease Type 1 (CMT) is an inherited neuropathy with known genetic heterogeneity, with at least one autosomal dominant form (CMT Type 1b) linked to the Duffy region of chromosome 1. Autosomal dominant families not demonstrating linkage to the Duffy blood group marker have been designated CMT Type 1a. We report linkage of six CMT Type 1a families to the chromosome 17 markers EW301 (D17S58) and pA10-41 (D17S71) with maximum LOD scores of zeta = 10.49 at theta (maximum recombination fraction) = 0.05 and zeta = 7.36 at theta = 0.06, respectively.

Charcot-Marie-Tooth Disease↗
PubMed1989

Cyclic AMP-dependent melatonin production in Y79 human retinoblastoma cells.

Melatonin is rhythmically synthesized in some vertebrate retinas and has been implicated in the regulation of key rhythmic events in the photoreceptor-pigment epithelial complex. In human retina, melatonin is present; however, no information exists on the cellular regulation of this hormone. We report here that the established human retinoblastoma cell line Y79 synthesizes and releases melatonin. Treatments that elevate cyclic AMP (cAMP) levels (forskolin, 8-Br-cAMP, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine) all stimulate melatonin release from static cultures of Y79 cells. Other 8-bromo nucleotide analogues (cyclic GMP, ATP, and AMP) are not effective. These results suggest that Y79 human retinoblastoma cells require a cAMP-dependent mechanism for melatonin biosynthesis similar to that described previously in other vertebrates. This is the first demonstration of melatonin release from a cultured human cell line. These results support the idea that human retinal cells share homologies with pineal cells, as suggested by the condition trilateral retinoblastoma.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Specificities of afferents reinnervating cat muscle spindles after nerve section.

1. We have made quantitative assessments of the sensory reinnervation and recovery of peroneus brevis muscle spindles following section and epineurial repair of the common peroneal nerve. After 6-50 weeks recovery, single-unit, dorsal-root recordings were made of the responses to ramp-and-hold or sinusoidal stretch of the reinnervated spindles, which were subsequently examined in teased, silver preparations. 2. Assessments of recovery used data obtained from cross-union experiments in which foreign afferents (including Ib) were given the opportunity of reinnervating spindles in the absence of their native (Ia, spindle II) afferents; and from an examination of tenuissimus spindles reinnervated by Ia and spindle II afferents in the absence of Ib afferents. These studies revealed: (i) that regenerating Ib afferents can terminate in sites originally occupied by the endings of Ia or spindle II afferents, and respond to stretch like normal Ia and spindle II afferents; (ii) that Ib and spindle II afferents reinnervating spindles are histologically identical apart from diameter range; and (iii) that some cutaneous afferents can reinnervate spindles and give highly abnormal, phasic stretch responses. 3. Recovery of afferents reinnervating spindles was marked by increases in conduction velocity and proportions firing tonically, but their firing rates at the three phases of ramp-and-hold stretch were considerably lower than normal and showed no tendency to increase. 4. Some relatively fast afferents that gave spindle II-type responses were identified as Ib afferents reinnervating secondary-ending sites; conversely, some relatively slow afferents that gave Ia-type responses were identified as spindle II afferents reinnervating primary-ending sites. 5. The estimated loss of spindle afferents from tenuissimus after nerve section (52% Ia, 49% spindle II) was considerably less than the estimated loss of these afferents from peroneus brevis after section of the common peroneal nerve (79% Ia, 86% spindle II). The proportion of spindles in tenuissimus reinnervated by free-ending afferents was also much lower (22%) than in peroneus brevis (73%). These differences are partly attributed to the greater size and degree of afferent complexity of the common peroneal nerve. 6. Similar proportions of spindles in peroneus brevis were reinnervated by Ia and Ib afferents after both partial (27% Ia, 20% Ib) and complete (21% Ia, 20% Ib) section of the common peroneal nerve.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1989

Genetic analysis of eight loci tightly linked to neurofibromatosis 1.

The genetic locus for neurofibromatosis 1 (NF1) has recently been mapped to the pericentromeric region of chromosome 17. We have genotyped eight previously identified RFLP probes on 50 NF1 families to determine the placement of the NF1 locus relative to the RFLP loci. Thirty-eight recombination events in the pericentromeric region were identified, eight involving crossovers between NF1 and loci on either chromosomal arm. Multipoint linkage analysis resulted in the unique placement of six loci at odds greater than 100:1 in the order of pter-A10-41-EW301-NF1-EW207-CRI-L581-CRI-L946 -qter. Owing to insufficient crossovers, three loci--D17Z1, EW206, and EW203--could not be uniquely localized. In this region female recombination rates were significantly higher than those of males. These data were part of a joint study aimed at the localization of both NF1 and tightly linked pericentromeric markers for chromosome 17.

Chromosome Mapping↗
PubMed1988

Factors related to ovulation method efficacy in three programs: Bangladesh, Kenya, and Korea.

Sociodemographic and reproductive health data were gathered on approximately 200 acceptors in each of three programs offering the Ovulation Method of Natural Family Planning. The programs were located in Bangladesh, Kenya, and Korea. In addition, a one year follow-up was attempted to assess continuation and efficacy. Descriptive data show a variety of religious, educational, income, family, and family planning backgrounds among acceptors. Life table analyses of reported unplanned pregnancy occurrence among spacers and limiters combined was 15% at 12 months in Bangladesh, 11% in Kenya and 13% in Korea. The pregnancy rate at 12 months for all pregnancies, planned and unplanned, was 27.0, 26.0, and 23.7, respectively. In Bangladesh 37 of the 48 unplanned pregnancies were user-related as were all of the 14 unplanned pregnancies in Kenya and 17 of the 20 in Korea. Method failure was the reported cause of pregnancy in only 2 of the 83 unplanned pregnancies. A major aspect of this study was the assessment of higher risk population subgroups; increasing age, education, previous pill use and previous family planning are significantly associated with fewer unplanned pregnancies while religion, attendance as a couple, family planning intention, size and source of referral do not have a demonstrated impact on pregnancy occurrence. The time of entry into the data set in relation to time of initial NFP acceptance may be an important variable in assessing OM effectiveness.

Adolescent↗