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Biomedical subjects

J Wilson

Publications and source records attributed to J Wilson.

At least 19 recordsLinked to original sources
PubMed1992

Treatment of hypertension induces a fall in platelet basal cytoplasmic calcium concentration without influencing platelet aggregation.

The relationship between blood pressure and platelet basal cytoplasmic calcium concentration ([Ca2+]i) and platelet sensitivity to aggregating agents in hypertension has been investigated in hypertensive patients and normotensive subjects. Ten severely hypertensive patients whose blood pressures were poorly controlled with metoprolol, were given calcium antagonist (either nifedipine or felodipine) as a second line agent. Venous blood samples were collected at each treatment phase for measurement, in whole blood, of platelet aggregation in response to ADP and collagen, and of basal [Ca2+]i using fura-2. Control of blood pressure by the combination of metroprolol and a calcium antagonist induced a significant decrease in median [Ca2+]i from 116 (76-181) to 73 (60-83) nM, which was similar to the median value of 70 (61-80) nM obtained in 14 normotensive subjects. Overall [Ca2+]i correlated with mean blood pressure (r = 0.51). Treatment of hypertension with calcium antagonist did not change the response of platelets to collagen or ADP. The results confirm that effective treatment of hypertension significantly reduced basal [Ca2+]i in platelets but raise doubts whether elevated basal [Ca2+]i is necessarily the sole mechanism by which the sensitivity of platelets to aggregatory agents is increased in hypertension.

Adult↗
PubMed1992

Isolation of transglutaminase-reactive sequences from complex biological systems: a prominent lysine donor sequence in bovine lens.

The transglutaminase (protein-glutamine: amine gamma-glutamyltransferase, EC 2.3.2.13)-catalyzed cross-linking of proteins in biological systems can often be inhibited by inclusion of small primary amines or glutamine-containing peptides, which act as site-specific blockers of the relevant acceptor (i.e., glutamine) and donor (i.e., lysine) functionalities of the natural substrates. Compounds such as dansylcadaverine and dansyl-epsilon-aminocaproyl-Gln-Gln-Ile-Val are particularly useful in sorting out acceptor-donor relationships among lens crystallins. Apart from its fluorescent properties, the dansyl hapten offered special advantages as a "handle" for the rapid isolation of transglutaminase targets even in the complex system of lens cortical homogenate. The dansylated peptide was incorporated into bovine lens proteins under the influence of the Ca(2+)-activated intrinsic transglutaminase and, after digestion by endoproteinase Glu-C, the tracer-containing fragments were isolated by affinity chromatography on an anti-dansyl antibody column. The major fluorescent peak was isolated by HPLC and sequenced by Edman degradation, which yielded phenylthiohydantoin amino acid derivatives for the first 10 cycles, EKPAVTAAPK, and none for the next 2. The sequence, corresponding to residues 165-174 of alpha B-crystallin, unambiguously identifies the known carboxyl-terminal domain, EK-PAVTAAPKK, as the prominent lysine-donating fragment in bovine lens.

Amino Acid Sequence↗
PubMed1992

N epsilon(gamma-glutamyl)lysine crosslinks in the blood clot of the horseshoe crab, Limulus polyphemus.

Clots were allowed to form in samples of whole blood taken from the American horseshoe crab, Limulus polyphemus, in the absence and presence of dansylcadaverine (16), and were analyzed for their contents of N epsilon(gamma-glutamyl)lysine and gamma-glutamyl-dansylcadaverine. Clots obtained without dansylcadaverine yielded significant amounts of N epsilon(gamma-glutamyl)lysine product. Clots formed in the presence of dansylcadaverine yielded only gamma-glutamyl-dansylcadaverine. Formation of these products reflects on the activity of transglutaminase released from the blood cells during coagulation.

Animals↗
PubMed1992

Copper 7 IUCD.

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Female↗
PubMed1992

Amide bond cleavage monitored continuously through detection of a dansylcadaverine leaving group.

The transglutaminase-catalyzed incorporation of the fluorescent amine, dansylcadaverine, into casein derivatives, such as N,N-dimethylcasein, is accompanied by a large increase in intensity of emission (Lorand et al., Anal. Biochem. 44, 221-231, 1971). We have sought to make use of this sensitive detection device for the continuous, on-line monitoring of an amide-splitting reaction in which dansylcadaverine served as the leaving group. The transglutaminase-coupled test system comprised gamma-glutamyldansylcadaverine as the first substrate and gamma-glutamylamine cyclotransferase as the enzyme responsible for releasing dansylcadaverine from the gamma-amide. At close to saturating levels of transglutaminase, the measured rate of increase of fluorescence, i.e. the steady-state rate of dansylcadaverine incorporation into N,N-dimethylcasein, showed a near-linear relationship with the concentration of gamma-glutamylamine cyclotransferase present in the assay mixture. The general approach developed may be applicable to the assay of other amide cleaving enzymes.

Amides↗
PubMed1992

Hyperinsulinaemia causes a preferential increase in hepatic P4501A2 activity.

Male NEDH (New England Deaconess Hospital) rats were transplanted with a radiation-induced tumour from a donor male rat and were killed 18 days following transplantation. At the time of killing the insulinoma-bearing animals were severely hypoglycaemic but plasma ketone levels were normal. Insulinoma-bearing animals exhibited higher hepatic O-deethylation of ethoxyresorufin and N-demethylation of ethylmorphine activities when compared to control animals. Similarly, hepatic microsomal preparations from insulinoma-bearing rats were more efficient than control animals in converting the promutagen 2-amino-6-methyldipyrido[1,2-a:3',2']imidazole (Glu-P-1) to mutagenic intermediates in the Ames test. Immunoblot analysis employing polyclonal antibodies against the P4501A and P453A families revealed that insulinoma-bearing rats had higher hepatic P4501A2 apoprotein levels. No major differences in P4503A1 apoprotein levels between insulinoma-bearing and control rats were noted. Subcutaneous administration of insulin to male Wistar rats gave rise to a modest increase in ethoxyresorufin O-deethylase activity and in the ability to activate Glu-P-1 to mutagens in the Ames test. Immunoblot analysis revealed an increase in hepatic P4501A2 apoprotein levels following the treatment with insulin. It is concluded that insulinoma-bearing rats display high P4501A2 activity and the hyperinsulinaemia that characterize this condition is responsible for the effect. Moreover, administration of insulin to other strains of rat, such as Wistar, also enhances P4501A2 activity, presumably as a result of hyperinsulinaemia.

Animals↗
PubMed1992

The 5'-flanking region of the human calreticulin gene shares homology with the human GRP78, GRP94, and protein disulfide isomerase promoters.

Calreticulin (CR) is a calcium binding protein that resides in the endoplasmic and sarcoplasmic reticulum and is reactive with human Ro/SS-A autoimmune sera. We have used human CR cDNA to isolate a human 6-kilobase genomic clone that contains 529 base pairs upstream of the presumed transcription start site, 9 exons, 8 introns, and several hundred base pairs 3' of a polyadenylation sequence. Analysis of the human CR promoter region reveals a number of potential regulatory sites also found in the human GRP78, GRP94, and protein disulfide isomerase promoters, including multiple Sp1 and CCAAT consensus sequences, an AP-2 recognition sequence (absent in protein disulfide isomerase), and multiple GC-rich areas. DNA footprint and gel shift analysis on the CR 5'-flanking region demonstrates an area that is bound by protein found in human but not murine nuclear extracts. This sequence is homologous with previously determined regulatory sequences of the human GRP78 and GRP94 promoters. These data indicate that CR, GRP78, GRP94, and protein disulfide isomerase may in part have similar transcriptional regulation and suggest that their gene products while structurally distinct may have similar functions or co-functions. These observations are of additional interest as all four of these genes encode acidic proteins that localize to the endoplasmic reticulum.

Amino Acid Sequence↗
PubMed1992

Zidovudine serum, cerebrospinal fluid, and brain concentrations following chronic administration of a new zidovudine formulation via an implantable pump in dogs [corrected].

Zidovudine (AZT), prepared as an alkaline solution, was administered iv and intraarterially (ia) by continuous infusion via an implantable pump in dogs. The AZT serum and cerebrospinal fluid (CSF) concentrations were measured over a 28-day treatment period by HPLC. Terminal brain AZT concentrations were also measured. Control (vehicle only) animals were also studied. All animals were evaluated for pathological changes associated with the AZT and vehicle infusions in catheterized vessels and other organs. In the iv AZT treatment group, serum AZT concentrations were relatively constant, with individual coefficients of variations (%CV) of 20% or less. Mean CSF:serum and brain:serum AZT concentration ratios were 0.149 and 0.212, respectively. In the ia AZT treatment group, serum AZT concentrations were more variable than in the iv group, with %CV ranging from 22 to 79%. The fluctuations in serum concentrations were attributed to temporary blockages of the outflow catheter. Mean CSF:serum and brain:serum AZT concentration ratios were 0.126 and 0.249, respectively. Pathological changes, similar in both control and treatment groups, included endothelial denudation and myointimal proliferation at the infusion sites. The conclusions of the study are (1) steady-state greater than 1 microM AZT serum concentrations can be maintained chronically by use of an implantable pump containing a basic pH AZT solution; (2) ia delivery of AZT did not increase central nervous system uptake compared with iv administration; and (3) morbidity associated with the infused solutions does not seem to be a limitation for this mode of therapy.

Animals↗
PubMed1992

Hemodynamic effects of nisoldipine, a highly specific calcium antagonist, in patients with acute myocardial infarction.

The aim of the study was to investigate the hemodynamic effects of a short-acting, potent, highly specific calcium antagonist, nisoldipine, in patients with acute myocardial infarction. Twenty-four patients were selected on the basis of an elevated wedge pressure and/or elevated blood pressure, less than 12 hours after the onset of symptoms. Patients were randomized to receive either placebo or low-dose nisoldipine (2 micrograms/kg) as a single intravenous injection over a 3-minute period. hemodynamic effects were monitored for 20 minutes, and thereafter patients were crossed over to the other agent after the preserved parameters had returned to baseline. An open-label study using double the dose of nisoldipine in 20 patients who had not reacted adversely to low-dose nisoldipine followed. Standard hemodynamic monitoring showed that peak effects of nisoldipine were reached at 5 minutes, with some residual effect at 20 minutes, and it took up to 60 minutes to return to baseline. Both doses of nisoldipine had similar effects: a fall in the systemic vascular resistance by about 600 units, variable tachycardia, little or no change in the wedge pressure, a decrease in the arterial pressure, an unchanged rate-pressure product, and an increase in ejection fraction. Tachycardia of more than 15 beats/min resulted in 5 of 24 patients with low-dose nisoldipine and 6 of 20 patients with high-dose nisoldipine. In view of the risk of tachycardia, nisoldipine seems unsuitable for use in the acute phase of myocardial infarction.

Adult↗
PubMed1992

An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome.

We present clinical and laboratory data from a patient with Waardenburg's syndrome type II comprising iris heterochromia and deafness, complicated by Hirschsprung's disease--a known association--and an unusual demyelinating peripheral neuropathy--a unique association. The neuropathy is characterised by excessive focal folding of myelin sheaths. It is our view that, although both disorders could represent the consequences of neural crest embryopathy, it is more likely that they are associated by chance.

Child↗
PubMed1992

Computer-aided analysis of intraoral ulcerative lesions.

At the present time there is no objective method to evaluate oral ulcerative lesions for degree of inflammation, surface area, or other parameters of healing. The capability of infrared photography to uniquely image the inflammatory process associated with oral lesions and the use of image-processing technology for parameter analysis was investigated. Lesions were compared cross-sectionally and over time for area of tissue degeneration, active inflammation, and intensity of inflammation with respect to adjacent tissue. Eight subjects were available for study. Standard black and white, color, and black and white infrared photographs were taken in accord with study protocols. A reflectance standard was included in each photograph to normalize the background intensity. A video camera was used to enter the data into a microcomputer image processing system. Quantitative data obtained included area of ulceration and erythematous halo, inflammatory intensity changes over time, and intensity with respect to adjacent tissue. This computer-aided photographic technique was able to quantify healing progression and intensity parameters associated with intraoral inflammatory lesions.

Adult↗
PubMed1992

The generation of ordered sets of cosmid DNA clones from human chromosome region 11p.

We describe progress in a continuing project aimed at the generation of an overlapping cosmid DNA clone map of the short arm of human chromosome 11. The automated procedures used to prepare DNA samples and the computerized data collection and recording systems are described. We also demonstrate the use of the clones as reagents for the rapid isolation of genomic DNAs containing smaller probed regions. We have isolated approximately 4700 human cosmid DNA clones from mouse/human hybrid cell lines that contain predominantly human chromosomal region 11p. Of the DNA in the cell lines, 60% is derived from this chromosomal region, and the remaining 40% is derived from regions of chromosomes 3, 19, and 20. A total of 4159 clones have been fingerprinted to identify potential overlaps, and we have developed 535 sets ("contigs"). Using random modeling, it is estimated that 65% of 11p must be contained in the analyzed cosmids. The database of clones has been used to identify single or overlapping clones from noncosmid DNA probes. Examples are presented. It is proposed that cosmid reference filters be distributed to requesting laboratories.

Chromosome Mapping↗
PubMed1992

Injectable bioglass as a potential substitute for injectable polytetrafluoroethylene.

Injectable polytetrafluoroethylene (Teflon) and collagen have inherent problems that may prevent their long-term success. In search of a different injectable biomaterial we confirmed in rabbits the safety of injected Bioglass particles suspended in sodium hyaluronate. A second study was performed testing the ability of the Bioglass suspension to increase urethral resistance in pigs. Bioglass particles in suspension have the potential to substitute for polytetrafluoroethylene or collagen in the treatment of urinary incontinence or vesicoureteral reflux.

Animals↗
PubMed1992

Progressive and imaginal relaxation training for elderly persons with subjective anxiety.

Elders exposed to either progressive or imaginal relaxation procedures reported significant relaxation effects and showed improvement on measures of personal functioning. The results of the Physical Assessment Scale of the Relaxation Inventory indicated that relaxation responses were acquired within and across sessions. Large, consistent changes in relaxation occurred in all 4 sessions. The Symptom Checklist-90-R, which measures self-reported personal adjustment, showed significant positive changes following relaxation training and at 1-month follow-up. Elders who imagined muscle tension release profited as much as those engaged in actual muscle tension-release activities. This finding is of importance for older adults who may experience physical limitations that contraindicate muscle-tension-release procedures.

Aged↗
PubMed1992

Non-progressive paraparesis in children with congenital ligamentous laxity.

We present clinical data from 11 children with generalised joint laxity complicated by signs of pyramidal dysfunction confined to the lower limbs. Gait abnormalities were observed at the time they started walking or soon afterwards. In some, there was delay in locomotor development but all except one were mentally normal. The neurological component of the condition was non-progressive, and sensory impairment with sphincter involvement was observed in only one case in whom there was radiological evidence of myelomalacia. Whilst co-existing ligamentous laxity and pyramidal dysfunction in the lower limbs may be coincidental, it is also possible that joint laxity is a pre-condition for developing neurological abnormality in the legs because of hypermobility of the vertebral column which thereby damages the spinal cord.

Child↗
PubMed1992

Autosomal recessive microcephaly with severe psychomotor retardation.

Autosomal recessive microcephaly has long been recognized in association with normal early motor development and mild to severe mental retardation. We report three sibling pairs with microcephaly and severe neurological impairment. These cases and other sibling pairs reported in the literature illustrate that microcephaly with spasticity and severe mental retardation may also have autosomal recessive inheritance. Furthermore this severely affected group of patients forms a significant proportion of cases of genetic microcephaly. We looked for specific morphological features to identify these forms of genetic microcephaly for genetic counselling, but failed to find characteristic abnormalities among our group of patients.

Adolescent↗