Biomedical subjects
Publications and source records attributed to I Patel.
Female twins concordant for thanatophoric dysplasia are presented. Monozygosity was confirmed using minisatellite DNA genetic fingerprinting. The evidence supporting new dominant mutations as the likely cause of thanatophoric dysplasia is reviewed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The replication origin gamma of plasmid R6K in certain miniplasmids is kept silent by a silencer RNA. We have identified a major and three minor transcripts that are synthesized in a direction antiparallel and complementary to the silencer RNA. The major RNA, called the activator, is essential for replication from ori gamma. The complementary nature of the activator and silencer RNAs strongly suggests that the former is a target of the latter. We have also discovered that the initiator protein is a sequence-specific double-stranded RNA-binding protein that accelerates the rate of activator-silencer hybrid formation. Thus the efficient silencing of ori gamma can be explained by silencer RNA-activator RNA hybrid formation that is driven to completion by the initiator protein.
This paper describes an inexpensive and relatively simple procedure to prepare high-performance size-exclusion columns from laboratory-packed or commercially pre-packed high-performance liquid chromatography columns by chemical deactivation of the surface of the silica packing material. The columns can be prepared quickly and reproducibly, they are chromatographically as efficient as high-performance size-exclusion columns commercially available, and are prepared at a fraction of the cost. Examples of the separation of proteins, peptides and polysaccharides on laboratory-prepared columns with differing permeation characteristics are illustrated and discussed.
Five of the most variable loci detected in human DNA by hybridization with DNA fingerprint probes have been cloned and characterized. Each locus consists of a tandem-repetitive minisatellite, with repeat units ranging in length from 9 to 45 base pairs depending on the locus. All of these cloned minisatellites act as locus-specific hybridization probes, and detect extremely variable Mendelian loci with heterozygosities ranging from 90 to 99%. These five hypervariable loci, together with a previously-isolated minisatellite designated p lambda g3, are dispersed over four autosomes (chromosomes 1, 5, 7 and 12). Syntenic pairs on chromosomes 1 and 7 show no detectable pair-wise linkage, and thus these hypervariable loci show no evidence of clustering within the genome and should provide valuable markers for mapping inherited disease. The locus-specific minisatellites act as very sensitive hybridization probes, and can be pooled to detect several hypervariable loci simultaneously. The applications of these probes in individual identification, paternity testing and analysis of cell chimaerism are discussed, and are illustrated by an analysis of forensic specimens from two victims who had been sexually assaulted and murdered.
Explore the source record for details and available documents.
The chromosome of R6K contains multiple origins of replication. The origin gamma is infrequently used in the original plasmid and remains "silent" in certain miniplasmid derivatives. The inactivation of the origin is caused by a natural origin silencer located adjacent to the minimal ori gamma sequence. The silencer functions in cis and has no trans activity. It has functional polarity and works only in one orientation when present immediately downstream from ori gamma. The silencer apparently initiates an RNA that invades ori gamma and turns it off either by competing with a primer RNA or by disrupting ori gamma structure. As predicted, removal of the silencer blocks the synthesis of silencer RNA and derepresses the origin.
The replication initiator protein of the plasmid R6K binds to seven contiguous 22 bp direct repeats that form an indispensable part of the three replication origins alpha, beta, and gamma. Binding of the initiator to the direct repeats induced a marked bending of the region of gamma replication origin. Binding of the initiator also promoted unwinding of the origin DNA by at least two turns. Distamycin appeared to antagonize the binding of the initiator to the seven 22 bp direct repeats. At the appropriate DNA and protein concentrations the initiator enhanced topoisomerase-induced catenation of the origin containing supercoiled DNA but not of DNA lacking the origin sequence. Thus, the initiator protein caused significant changes in the secondary and tertiary structures of the replication origin.
Two unusual patients with chronic, undifferentiated schizophrenia committed acts of ocular self-mutilation. The types of patients who perform acts of self-inflicted ocular injuries are described, with particular emphasis on individuals suffering from post-traumatic stress disorder (PTSD). A discussion of these cases, as well as a review of the literature on the more common forms of self-mutilation, is presented.
The concentrations of serum total cholesterol, high density lipoprotein-cholesterol, and triglycerides have been measured in 7735 men aged 40 to 59 years who were drawn from general practices in 24 towns in England, Wales, and Scotland. The distribution of these blood lipids, their interrelations and their association with age, social class, body mass index, cigarette smoking, alcohol intake, and physical activity at work have been examined. Body mass index emerges as the factor most strongly associated with these three blood lipids. Serum total cholesterol increased with increasing body mass index until about 28 kg/m2 but thereafter showed no further rise. The relation between body mass index and high density lipoprotein-cholesterol was negative and linear; that between body mass index and triglycerides was positive and linear. The inverse relation between high density lipoprotein-cholesterol and triglycerides was independent of the fact that both were related to body mass index. Alcohol intake was associated with increased high density lipoprotein-cholesterol concentrations and cigarette smoking with lowered high density lipoprotein concentrations; the association with alcohol appeared to be dominant. No significant trends with age were observed for the three blood lipids. In this population, body mass index is closely associated with the concentration of blood lipids but its effects are probably indirect and mediated by a complex of dietary and other factors.
Total cholesterol, high density lipoprotein (HDL)-cholesterol and triglycerides were measured fasting and at 20, 40, 60, 120 and 180 min after a high-fat meal in 22 healthy subjects. Both HDL-cholesterol and total cholesterol fell during the first 20 min after the meal whereas the mean triglyceride level increased during the observation period. In 8 of the subjects the maximum triglyceride level was reached before the end of the observation period and their fasting HDL-cholesterol level was significantly higher than in the rest of the subjects. The higher the fasting HDL-cholesterol concentration, the more rapidly the triglyceride levels returned towards initial values. The study supports the concept that the degradation rate of triglyceride-rich particles is dependent on the HDL-cholesterol level. It also suggests the use of non-fasting triglyceride values in addition to HDL-cholesterol as independent predictors in longitudinal studies for CHD.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Platelets from patients with acute myelogenous leukemia, both before and after remission induction, were evaluated for their ability to incorporate D-[U-14C]glucose into the four amino acids, glutamine, asparagine, glutamic acid, and aspartic acid. Normal platelets incorporated about 80% of the activity into the amides, glutamine and asparagine, and only 20% into their respective amino acids, glutamic acid and aspartic acid. Platelets from patients with acute myelogenous leukemia in the acute stage showed a reversal of this pattern, which then returned to normal during remission. However, the concentration of amino acids was higher than normal, suggesting that remission platelets behaved like a young cell population. The abnormal pattern of labeling could be interpreted as a defect in the platelet citric acid cycle thereby compromising its energy source.
Resting fibrinolytic activity and the response of the fibrinolytic system to venous occlusion were studied in a group of healthy middle-aged men. All subjects showed increased fibrinolytic activity but of varying degrees. There was a linear relationship between resting and occluded levels of fibrinolytic activity but many subjects with lower levels of fibrinolytic activity showed an anomalous response. Responses over the expected level were more common than unexpectedly low levels of response. Fibrinogen and plasminogen concentrations were inversely correlated with fibrinolytic activity.
Explore the source record for details and available documents.