Search PubMed⌕ Search

Biomedical subjects

T J Robinson

Publications and source records attributed to T J Robinson.

At least 73 records · Page 4Linked to original sources
PubMed1990

Chromosomal assignment and regional localization of myeloperoxidase in the mouse.

Using a rat x mouse somatic cell hybrid that contains chromosome 11 as the only mouse material, we have shown that myeloperoxidase, which maps to human chromosome 17, maps to mouse chromosome 11. Regional assignment of the gene by in situ hybridization localized Mpo to the region C-E1, with a peak at band 11C. These results further confirm and extend observations on the remarkable homology between human chromosome 17 and mouse 11.

Animals↗
PubMed1989

Rodent common fragile sites: are they conserved? Evidence from mouse and rat.

Nineteen fragile sites induced by aphidicolin in lymphocyte cultures from the laboratory mouse are documented. These sites are compared with previously described fragile sites induced in mouse fibroblast systems, and then with those reported on chromosomes which have been evolutionarily conserved between the mouse and the laboratory rat. Of a total of 38 fragile sites thus far identified in mouse fibroblasts and lymphocytes, only 4 sites are common to the two cell types; 34 sites show no correspondence of loci. The reason for this discrepancy is unclear, but it is possible that these data may indicate some degree of tissue specificity of fragile site expression in the mouse. Eight autosomes in the mouse and rat retain straightforward and nearly complete banding homology. To test the hypothesis that fragile sites are conserved between the two species, we compared these eight autosomes with regard to number and distribution of fragile site loci. A total of 30 fragile sites is distributed over the conserved chromosomes. Only 4 (possibly 5) are common to both species; 18 are found in the rat but not the mouse, and 4 are found in the mouse but not the rat. Of the 4 shared sites, notable differences in frequency of expression exist. Our comparisons show that: (1) a small number of fragile sites is conserved; (2) a large number of fragile sites is not conserved, and (3) some sites which are conserved are quite different in the frequency at which they are expressed in the two species, indicating that the sites themselves may have undergone evolutionary change.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Molecular dissection of a contiguous gene syndrome: frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated "island" in the Miller-Dieker chromosome region.

The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13. Twelve anonymous DNA markers were tested against a panel of somatic cell hybrids containing 17p deletions from seven MDS patients. All patients, including three with normal karyotypes, are deleted for a variable set of 5-12 markers. Two highly polymorphic VNTR (variable number of tandem repeats) probes, YNZ22 and YNH37, are codeleted in all patients tested and make molecular diagnosis for this disorder feasible. By pulsed-field gel electrophoresis, YNZ22 and YNH37 were shown to be within 30 kilobases (kb) of each other. Cosmid clones containing both VNTR sequences were identified, and restriction mapping showed them to be less than 15 kb apart. Three overlapping cosmids spanning greater than 100 kb were completely deleted in all patients, providing a minimum estimate of the size of the MDS critical region. A hypomethylated island and evolutionarily conserved sequences were identified within this 100-kb region, indications of the presence of one or more expressed sequences potentially involved in the pathophysiology of this disorder. The conserved sequences were mapped to mouse chromosome 11 by using mouse-rat somatic cell hybrids, extending the remarkable homology between human chromosome 17 and mouse chromosome 11 by 30 centimorgans, into the 17p telomere region.

Biological Evolution↗
PubMed1988

A radioimmunoassay for fluorogestone acetate (FGA) and its application to the measurement of plasma FGA and progesterone in ewes treated with FGA-impregnated intravaginal sponges.

Simultaneous concentrations of endogenous progesterone and exogenous FGA have been measured in ewes treated with FGA-impregnated intravaginal sponges at several times relative to the expected time of release of LH. First, a direct double antibody radioimmunoassay (RIA) for FGA, with good precision, sensitivity and reproducibility, was developed and validated. An oxime derivative was prepared and then conjugated to human serum albumen at the 3-position to produce the antigen. Antibodies raised in New Zealand White rabbits showed little cross-reactivity with related steroids. FGA was estimated in extracted and unextracted plasma; results were indistinguishable. Second, sponges impregnated with 40 mg FGA were inserted into 20 anoestrous crossbred ewes for 12 days; 500 i.u. pregnant mare serum gonadotrophin (PMSG) was injected at withdrawal. Similar sponges were reintroduced into four ewes at each of the intervals 1, 3, 5, and 7 days later; three ewes served as controls. Plasma concentrations of progesterone and FGA were estimated by RIA daily during treatment and at intervals of 2 h for 12 h and at 18 and 24 h after withdrawal. The plasma profiles of FGA during the two successive periods of insertion were remarkably similar. A concentration of 3.0 ng/ml (s.e.m. +/- 0.22) was attained on day 1, falling to 1.5 ng/ml (+/- 0.15) by day 4. Thereafter, the concentration was maintained at 1.1 ng/ml (+/- 0.08). Plasma progesterone concentrations were at basal levels of less than 0.2 ng/ml during the first (acyclic) period of sponge insertion. During the second (cyclic) period there was a marked difference related to the time of sponge insertion. Insertion on day 1 (before LH release) resulted in complete inhibition of luteal activity; insertion on day 3, 5 or 7 was followed by apparently normal luteal function. There was no evidence of any feedback mechanism of exogenous progestagen on endogenous progesterone and no interaction. It is concluded that a 12-day treatment is needed in cyclic ewes for full synchronization and that sponges impregnated with 40 mg FGA will maintain an effective plasma concentration of greater than 1 ng/ml to the end of this period.

Animals↗
PubMed1988

Controlled sheep breeding: update 1980-1985.

This contribution to the Symposium concerns four topics which have been addressed in our laboratory over the past five years. First, the responses to a controlled light environment of Merino ewes and rams have been compared with those of two British breeds. The endocrinological patterns were similar in all breeds but cyclic ovarian activity and ram libido were different. While showing a degree of entrainment to photoperiod, the breeding patterns were much less rigidly controlled in the Merinos than in the others. Second, the effectiveness of establishment of a cervical reservoir of spermatozoa, in ewes in which oestrus and ovulation have been controlled, has been re-examined. This is highly dependent on the time of insemination relative to that of the release of LH. Maximum numbers are found when ewes are inseminated shortly after the LH peak, i.e. some 6-10 h after the onset of oestrus. Third, the quantitative and temporal endocrinological and behavioural events following standard, progestagen-PMSG treatment have been quantified. Contrary to earlier expressed beliefs, these events are remarkably predictable provided an intensive system of mating or detection of oestrus is used. The onset of oestrus in treated anoestrous crossbred ewes has a normal distribution, with a range of 24 h, centred around a mean of 33 h after withdrawal of a 30 mg Cronolone intravaginal sponge and injection of 500 i.u. PMSG. This period of time is dose-dependent. The LH peak occurs 4.5 +/- 0.7 h later and the times of onset of oestrus and of LH release are highly correlated (r = 0.93). Ovulation is some 24 h later again. Fourth, differences in the response of ewes to different batches of PMSG have been defined. While the three commercial preparations studied regularly induced ovulation in anoestrous ewes at doses of 250 i.u. and above, the quantitative responses varied greatly. One preparation would not induce multiple ovulation, even at high doses. There are differences in steroidogenesis and in pregnancy rates, associated with dose of PMSG and the consequent ovulation rate: the ideal would be for every ewe to shed two or three ova. A higher ovulation rate is acceptable, as early embryonic mortality generally reduces the litter size. This is particularly important in deep anoestrus. However, this does not solve the problem of breeding in early lactation.

Animals↗
PubMed1988

Cellobiose/mannitol sugar absorption test in patients with dermatitis herpetiformis: a preliminary report.

An abnormal cellobiose/mannitol ratio is present in new patients presenting with dermatitis herpetiformis and in patients who have never adhered to a strict gluten-free diet. In patients with dermatitis herpetiformis in remission on a strict gluten-free diet, small bowel absorption as measured by the cellobiose/mannitol ratio is normal. It is suggested that cellobiose/mannitol ratio absorption is a useful screening test for the intestinal abnormality associated with dermatitis herpetiformis and failure of the test to return to normal could suggest poor dietary compliance.

Adult↗
PubMed1988

Molecular detection of microscopic and submicroscopic deletions associated with Miller-Dieker syndrome.

Miller-Dieker syndrome (MDS), a disorder manifesting the severe brain malformation lissencephaly ("smooth brain"), is caused, in the majority of cases, by a chromosomal microdeletion of the distal short arm of chromosome 17. Using human chromosome 17-specific DNA probes, we have begun a molecular dissection of the critical region for MDS. To localize cloned DNA sequences to the MDS critical region, a human-rodent somatic cell hybrid panel was constructed which includes hybrids containing the abnormal chromosome 17 from three MDS patients with deletions of various sizes. Three genes (myosin heavy chain 2, tumor antigen p53, and RNA polymerase II) previously mapped to 17p were excluded from the MDS deletion region and therefore are unlikely to play a role in its pathogenesis. In contrast, three highly polymorphic anonymous probes, YNZ22.1 (D17S5), YNH37.3 (D17S28), and 144-D6 (D17S34), were deleted in each of four patients with visible deletions, including one with a ring chromosome 17 that is deleted for a portion of the single telomeric prometaphase subband p13.3. In two MDS patients with normal chromosomes, a combination of somatic cell hybrid, RFLP, and densitometric studies demonstrated deletion for YNZ22.1 and YNH37.3 in the paternally derived 17's of both patients, one of whom is also deleted for 144-D6. The results indicate that MDS can be caused by submicroscopic deletion and raises the possibility that all MDS patients will prove to have deletions at a molecular level. The two probes lie within a critical region of less than 3,000 kb and constitute potential starting points in the isolation of genes implicated in the severe brain maldevelopment in MDS.

Abnormalities, Multiple↗
PubMed1987

Multiple common fragile sites are expressed in the genome of the laboratory rat.

Splenic lymphocytes from Sprague Dawley and Fischer 344 rats were exposed to two chemicals known to induce common fragile site expression in man: fluorodeoxyuridine (in conjunction with the enhancing effects of caffeine) and aphidicolin. Of 39 sites that were significantly damaged in excess, 12 meet the criteria for fragility proposed in this investigation. Rat fragile sites appear to differ from those in man in that no common hierarchical frequency of expression is evident from the two methods of induction. In addition, a comparison of published cancer-specific chromosome breakpoints from a variety of rat tumors reveals little or no apparent concordance with the identified fragile sites. The rat is an animal model in which multiple common fragile sites can be induced and, as such, will be valuable for testing hypotheses concerning the biological basis of chromosomal fragility.

Animals↗
PubMed1987

The response of rams and ewes of three breeds to artificial photoperiod.

Rams and ewes of the Romney Marsh (N = 6), Dorset Horn (N = 8) and Australian Merino (N = 8) breeds were subjected to 4 successive periods of alternating 6 h light/18 h dark ('short' days) and 18 h light/6 h dark ('long' days) preceded by 16 weeks of 12 h light/12 h dark. The initial period was of 32 weeks (16 weeks 'short' days; 16 weeks 'long' days) and the next 3 were of 24 weeks (12 weeks 'short' days; 12 weeks 'long' days). Rams of all breeds showed a cyclic pattern of growth and regression of testes associated with plasma testosterone concentration, influenced by the change in light regimen 15-19 weeks previously. Sexual behaviour was also cyclic but lagged by some 6-7 weeks. The changes were greatest in the Romneys and least in the Merinos in which a higher degree of sexual activity was evident even when the testes were regressed (P less than 0.001). This was the major breed difference. All ewes of the Romney and Dorset breeds showed marked seasonality related to the imposed light regimen, whereas only 1 of the 4 Merinos did so. The mean peak of ovarian activity in the former 2 breeds coincided with that of maximum sexual activity of rams housed with them; that is, some 6 weeks after maximum scrotal volume. The rams and ewes were subjected to serial blood sampling episodes for plasma LH and testosterone and tested for plasma LH release following GnRH administration. There was little variation between breeds in LH concentration. Testosterone concentration varied greatly in the ram, highest levels associated with the developed phase of the testes and with maximum LH pulse frequency. The LH response to GnRH changed with respect to the state of the gonads. Maximal responses were observed in the developing phase of testicular growth although this variation was greater in the Romney and Dorsets than in the Merinos (P less than 0.001). In the ewes, maximal responses were seen in the follicular phase (P less than 0.001), with no difference between the luteal and acyclic phases. There were no breed differences. Plasma pooled from the serial blood sampling episodes was assayed for prolactin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Crohn's disease--is there a long latent period?

Four cases of Crohn's disease developing in adult females, who had been in close contact during their teens, are described. It is suggested that this could indicate an infective causation for Crohn's disease with a long latency.

Adult↗
PubMed1986

An international multi-clinic study comparing the therapeutic efficacy of colloidal bismuth subcitrate coated tablets with chewing tablets in the treatment of duodenal ulceration.

The results of a randomized, single-blind, multi-clinic study comparing the therapeutic efficacy and degree of oral staining of new colloidal bismuth subcitrate (CBS) coated tablets over 4 weeks of treatment in patients suffering from duodenal ulceration are reported. The data were collected from 9 clinics in the Netherlands, Belgium, Ireland, the United Kingdom, and Italy. The results from 94 patients treated with CBS coated tablets and 95 patients treated with CBS chewing tablets were statistically evaluated. Healing rates after 4 weeks of therapy appeared to be 76% for CBS coated tablets and 72% for CBS chewing tablets, so no statistically significant difference in therapeutic efficacy was seen. A highly significant degree of discolouration of all parts of the oral cavity was observed in patients treated with CBS chewing tablets, whereas only a few patients treated with CBS coated tablets experienced a slight staining of the tongue. Blood bismuth concentrations during the study had a range of less than or equal to 3 to 33 micrograms/l. The new CBS coated tablet form has an excellent patient compliance as compared to the chewing tablets.

Adolescent↗
PubMed1985

Plasma progesterone concentrations, ovarian and endocrinological response and sperm transport in ewes with synchronized oestrus.

Two experiments involving 24 and 54 Australian Merino ewes were conducted in which the establishment of a cervical population of spermatozoa and several endocrinological events were studied after several regimens for the synchronization of oestrus. Intravaginal sponges impregnated with 500 mg (Exp. 1) or 200, 400 or 600 mg (Exp. 2) progesterone resulted in the maintenance of plasma progesterone concentrations of 1.5-4.9 ng/ml over a 12-day insertion period compared with 1.9-6.9 ng/ml during dioestrus in control ewes. In Exp. 1 basal concentrations of less than or equal to 0.25 ng/ml plasma were attained by 4 h after sponge withdrawal and this decline was much more rapid than in normal luteolysis. This was associated with fewer spermatozoa recovered from the cervix 2 h after insemination, and PMSG had no significant effect. In Exp. 2 injection of a supplementary dose of progesterone at sponge withdrawal resulted in a rapid increase in plasma progesterone concentrations followed by an equally rapid decrease and an attenuation of the rise in plasma oestradiol-17 beta, the LH surge, and the onset of oestrus. The numbers of spermatozoa recovered 4 h after insemination were not increased, and PMSG had no significant effect. Two factors were significant, namely the dose of progesterone in the sponge (600 mg greater than 400 or 200 mg, P less than 0.05) and stage of oestrus when inseminated (mid- or late oestrus greater than early). The data demonstrated that an adequate dose of progesterone/progestagen incorporated into intravaginal sponges and accurate timing of insemination relative to the LH surge are the most important factors involved in penetration of the cervix by spermatozoa.

Animals↗
PubMed1984

Evolution of chromosomal variation in cottontails, genus Sylvilagus (Mammalia: Lagomorpha). II. Sylvilagus audubonii, S. idahoensis, S. nuttallii, and S. palustris.

Chromosomes from cultured fibroblasts of four cottontail species (Sylvilagus audubonii, 2n = 42; S. idahoensis, 2n = 44; S. nuttallii, 2n = 42; and S. palustris, 2n = 38) were analyzed using G- and C-banding techniques. The evolutionary restructuring of the genomes of these species was traced by comparing their banded chromosomes to those of Lepus saxatilis, a species of hare in which the leporid ancestral karyotype is thought to have been conserved. Chromosomal evolution appears to have proceeded primarily through changes in the amount and distribution of heterochromatin and through fixation of Robertsonian fusions. Excluding heterochromatic differences, S. audubonii and S. nuttallii are karyotypically very similar, as are S. aquaticus and S. palustris (previously reported). The genome of the taxonomically controversial species S. idahoensis, compared to other cottontail species, is markedly impoverished in C-band material. These data and those of cottontail species previously described in the literature are incorporated in two alternative phylogenetic schemes.

Animals↗