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Biomedical subjects

D Chambers

Publications and source records attributed to D Chambers.

At least 55 records · Page 3Linked to original sources

Characterization of TRP-1 mRNA levels in dominant and recessive mutations at the mouse brown (b) locus.

The mouse brown locus encodes a putative membrane-bound metalloenzyme, tyrosinase-related protein-1 (TRP-1). We have examined the effect on mRNA expression of the locus of a number of mutant alleles. The common null mutant allele, brown, produces wild-type levels of TRP-1 mRNA, which is nonfunctional. Another recessive allele, cordovan-Harwell, has an intermediate, dark-brown phenotype and produces only very low levels of presumably normal TRP-1 mRNA. Two dominant alleles appear to act by killing the melanocyte in which they are expressed. One of them, Light, has normal size and amounts of TRP-1 mRNA. The other, White-based brown, produces no detectable TRP-1 mRNA. It has a gross DNA rearrangement at the 5' end, and we speculate that this results in activation of transcription of sequences not usually seen in melanocytes, and that this is toxic to the cell. The relationship between phenotype and molecular structure at the locus is discussed, and we draw some general principles applicable to other developmental genes.

Animals↗

Endometrial adenocarcinoma presenting as pituitary apoplexy.

The novel combination of disseminated primary endometrial adenocarcinoma and a symptomatic pituitary metastasis presenting as pituitary apoplexy is described for the first time. Pituitary apoplexy is an unusual manifestation of metastatic pituitary disease. The more common clinical features of pituitary metastases and an approach to their management are discussed. The usefulness of magnetic resonance imaging in assessing the base of skull is emphasised.

Adenocarcinoma↗

Methyl 2-[4-(2-chloroethyl)-2,3-dihydro-7-nitroquinoxalin-1-yl]benzoate from intramolecular cyclization of a nitroaromatic mustard.

C18H18CIN3O4, Mr = 375.81, orthorhombic, P212121, a = 11.000 (3), b = 8.023 (2), c = 19.316 (5) A, V = 1704.68 A3, Z = 4, Dm = 1.46 (1), Dx = 1.417 g cm-3, Mo Kalpha, lambda = 0.71069 A, mu = 1.82 cm-1, F(000) = 760, T = 293 (1) K, R = 0.051 for 985 [I greater than 2.5 sigma(I)] reflections. X-ray analysis confirms that the nitroaromatic mustard methyl N-(2-[bis(2-chloroethyl)amino]- 5-nitrophenyl)anthranilate undergoes rapid intramolecular cyclization, but the product is the 7-nitro rather than the 6-nitro derivative previously reported [Chambers & Denny (1986).

Antineoplastic Agents↗

Evidence for distinguishable transcripts of the putative testis determining gene (ZFY) and mapping of homologous cDNA sequences to chromosomes X,Y and 9.

Oligonucleotide sequences based on the amino acid sequence of the putative testis determining gene ZFY have been used to isolate a 1.3 Kb Hind III Y genomic DNA fragment CMPXY1 and three human testis cDNA sequences (CMPXY2, CMPXY3 and CMPXY4). These sequences detect at least four potential exons on the Y (Y1, Y3, Y4 and Y5), three on the X (X1, X2 and X3) and three of autosomal origin (A1, A2 and A3) as determined by comparing the fragments detected by different clones. Analysis with subfragments of CMPXY4 shows that Y3 is unique to the Y and that Y4 and X1 are homologous. Y5 and X3 are detected by the same subfragment of CMPXY4. This is also the case for Y1, X2, A1, A2 and A3. Thus these exons may contain further regions of homology between the X, Y and an autosomal locus. The X-linked sequences all lie in Xp21.2-Xp22.1 and studies with XX males have placed the Y-linked sequences in distal Yp adjacent to the Y-autosomal homologous sequence GMGY3. We have confirmed these localizations by in situ hybridization with CMPXY4 and have shown additionally that the autosomal sequences of both the CMPXY4 sequence and GMGY3 map to 9p22-9pter. Restriction analysis demonstrates that CMPXY1/XY2/XY3 differ in sequence from CMPXY4 at three restriction enzyme sites, thus suggesting that they are transcribed from different but closely related genes and that CMPXY4 must be either X-linked or autosomal in origin. This indicates that more than one of the loci containing ZFY-related sequences are transcribed and potentially fulfil functionally distinct roles in the human sex determining pathway. Northern blot analysis of human foetal testis RNA has shown that three low abundance transcripts of 5, 6 and 8 Kb can be detected by ZFY-related DNA sequences.

Base Sequence↗

Periodontal implications of orthodontic treatment in adults with reduced or normal periodontal tissues versus those of adolescents.

This longitudinal study monitored periodontal status in 20 adults and 20 adolescents undergoing fixed orthodontic treatment. Ten adults had generalized periodontitis and received periodontal treatment, including periodontal surgery, before orthodontic treatment. They also received periodontal maintenance at 3-month intervals during orthodontic treatment. The other 10 adults had normal periodontal tissues. Neither these latter adults nor the adolescents received periodontal maintenance during orthodontic treatment. Periodontal status was determined (1) at six standard sites before fixed appliances were placed (baseline), (2) at 1, 3, 6, 9, 12, and 18 months after appliances had been placed, and (3) 1, 3, 6, and 12 months after appliances had been removed. At each of these visits, these sites were assessed for plaque index, gingival index, bleeding tendency, and pocket depth. Loss of attachment between baseline and 3 months after appliances were removed and tooth loss were also determined. Complete data were obtained for 15 adolescents and 14 adults. During orthodontic treatment the adolescent group showed significantly more (p less than 0.05) periodontal inflammation and supragingival plaque than the adults; after appliances were removed, this pattern was no longer statistically significant. For loss of attachment, there were no significant differences among adolescents, adults with normal periodontal tissues, or adults with reduced but healthy periodontal tissues who had undergone treatment for periodontal disease. For tooth loss, three nonstudy site teeth with pockets deeper than 6 mm and/or furcation involvements were lost because of periodontal abscesses in the adult group treated for periodontal disease.

Adolescent↗

Postfusional latency in stereoscopic slant perception and the primitives of stereopsis.

Random dot stereograms of slanted surfaces were constructed, each representing one or two slanted surfaces in different relative arrangements and with different axes. Latency to fusion and from fusion to stereoscopic resolution was measured for each stimulus. It was found that latency to fusion was always very brief but that latency to stereoscopic resolution varied markedly, depending upon the orientation and arrangement of the stereoscopic surfaces. A gradient of discontinuities at a surface boundary produced an instant slant response for that surface, whereas a gradient of absolute disparities across the surface did not, except under conditions where vertical declination (a form of orientation disparity) was present. We conclude that stereopsis is not based on the primitives used in matching the images for fusion and that it is, at least initially, a response to disparity discontinuities which play no role in the fusion process. We also conclude that vertical declination is responded to globally as a slant around a horizontal axis but that other forms of orientation disparity are ineffective. The evidence from our experiments does not support the existence of a stereoscopic ability to respond globally to differences in magnification (or spatial frequency). It is suggested that stereoscopic perception of slant around a vertical axis is slow because it results from the integration of local processes.

Attention↗

Long-term survival rates after prolonged aortic cross-clamping with St. Thomas' Hospital cardioplegia.

Prolonged aortic cross-clamping (in excess of 120 min) was necessary in 154 cardiac surgical patients. St. Thomas' Hospital cardioplegia was used for myocardial preservation. Quantitative polarization microscopy enabling quantitative birefringence measurements to assess the change in birefringence of the muscle fibres in response to the addition of buffer containing ATP and calcium (i.e. myocardial contractility) was used to detect whether there had been any deterioration in right or left ventricular myocardium during the bypass period. 30 day survival was 90%, long-term (60 months) survival was 80%. In single valve replacements, patients with aortic valvular replacement had 100% survival up to 92 months, whereas patients with mitral valvular replacement had survival rates of 83% after 12 months and 27% after 60 months. Survival rates after 60 months were 89% for coronary artery bypass grafting, 80% for multiple valve replacements, and 74% for combined valvular and coronary artery bypass grafting surgery. Quantitative birefringence assessment of function showed that in the surviving patients 5% had functional deterioration during bypass whereas in the non-surviving patients 70% had functional deterioration. It may be concluded that after cardiac surgery necessitating prolonged aortic cross-clamping--once the initial operative problems are overcome--reasonable long-term results can be obtained by using St. Thomas' Hospital cardioplegia.

Bicarbonates↗

Potential antitumor agents. 46. Structure-activity relationships for acridine monosubstituted derivatives of the antitumor agent N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide.

A series of monosubstituted derivatives of the new antitumor agent N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide has been prepared, bearing methyl, methoxy, and chloro groups at available acridine positions. The physicochemical properties and antitumor activity of these compounds varied more with the position than with the nature of the substituent groups. The highest levels of both in vitro and in vivo antileukemic activity were shown by 5-substituted derivatives, while 7- and 8-substituted derivatives possessed the highest selectivity toward the HCT-8 human colon carcinoma line compared to the L1210 mouse leukemia line in vitro.

Aminoacridines↗

Perceived position and saccadic eye movements.

Data are reported which support the conclusion that saccades which occur 600 msec or more after the brief, presentation of a target stimulus are directed to its perceived position when that differs from both its retinal and spatial position.

Animals↗

Effect of self-administered daily irrigation with 0.02% SnF2 on periodontal disease activity.

To determine the effect on periodontal health of a daily self-administered irrigation with 0.02% stannous fluoride (SnF2) solution, 28 subjects who had moderate to advanced periodontitis were randomly divided into 3 groups: a control group (n = 9) which used no irrigation, a group (n = 8) which used a self-administered water irrigation device (Water Pik) daily with water (H2O group) and a group (n = 11) which used the Water Pik in a similar manner but with SnF2 solution (SnF2 group). All subjects were instructed in routine tooth brushing and flossing but received no other periodontal treatment. 4 study sites were selected from each patient which had pocket depths greater than 4 mm and bleeding upon probing. Plaque index, gingival index, bleeding tendency, pocket depth, loss of attachment, and microbiologic samples of subgingival plaque for morphologic determinations were collected from all study sites at baseline, 2, 6, and 10 weeks. A cross-over was then initiated for 2 additional monthly checks in which the H2O group changed to SnF2 and the SnF2 group was divided into 2 subgroups which either continued to use SnF2 or changed to H2O. The control group completed the study at the beginning of the crossover. The clinical data showed significantly more improvement in periodontal health during the first 10 weeks for the SnF2 group (p less than 0.01). After cross-over, the clinical data indicated the group that changed from H2O to SnF2 significantly improved their periodontal health, while the group that changed from SnF2 to H2O became worse. The microbiologic data showed trends which agreed with the clinical data during the first 10 weeks but were less significant. After cross-over, the %s of motile rods and spirochetes were too small (0-7%) to establish statistically significant changes considering the accuracy of the technique used.

Bacteria↗

Induced motion and oculomotor capture.

Three experiments investigating the basis of induced motion are reported. The proposition that induced motion is based on the visual capture of eye-position information and is therefore a subject-relative, rather than object-relative, motion was explored in the first experiment. Observers made saccades to an invisible auditory stimulus following fixation on a stationary stimulus in which motion was induced. In the remaining two experiments, the question of whether perceived induced motion produces a straight ahead shift was explored. The critical eye movement was directed to apparent straight ahead. Because these saccades partially compensated for the apparent displacement of the induction stimulus, and saccades to the auditory stimulus did not, we conclude that induced motion is not based on oculomotor visual capture. Rather, it is accompanied by a shift in the judged direction of straight ahead, an instance of the straight ahead shift. The results support an object-relative theory of induced motion.

Attention↗

St. Thomas' Hospital cardioplegia for myocardial preservation during prolonged aortic cross-clamping.

The effectiveness of St. Thomas' Hospital cardioplegia for myocardial preservation during prolonged aortic cross-clamping was analyzed in a clinical series of 100 consecutive cardiac surgical patients identified as having aortic cross-clamp times greater than 120 minutes. Hospital mortality from all causes was 8%, but only one of these 8 patients succumbed from immediate primary failure of the myocardial preservation protocol. Severe but reversible low cardiac output syndrome occurred in 5 patients, and in 4 of them there had obviously been a primary failure in cardiac protection. Peri-operative, clinically "silent" myocardial infarction could be demonstrated in retrospect by electrocardiographic criteria in 3 other patients. Post-operative complications occurred in 26 patients, many of them having several complications at the same time. Paired left ventricular and right ventricular prebypass and post-bypass biopsies processed for cytochemical and biophysical investigation were available from one third of the patients. Only 2 cases showed a severe deterioration. There was lack of correlation between the duration of aortic occlusion and operative mortality rate, incidence of peri-operative infarction, and occurrence of low cardiac output syndrome post-operatively. The results thus indicate that St. Thomas' Hospital cardioplegia is a very effective means of myocardial protection during prolonged periods of aortic cross-clamping.

Adolescent↗

Bone marrow transplantation for severe aplastic anaemia. A review of the Westminster experience of 24 cases.

Twenty-four patients have received bone marrow transplantation for severe aplastic anaemia at the Westminster Hospitals since 1974. Twelve patients are long term survivors. Infectious complications in association with graft rejection, graft versus host disease or prolonged neutropenia were the major cause of death. In the last 18 months the introduction of more effective conditioning regimes and Cyclosporin A as graft versus host disease prophylaxis has improved the survival rate to 85%. One patient has required regrafting for late graft failure without evidence of graft rejection.

Adolescent↗