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Biomedical subjects

J Gilbert

Publications and source records attributed to J Gilbert.

At least 55 records · Page 3Linked to original sources
PubMed1989

Modes of inhibition of protein kinase C by triphenylacrylonitrile antiestrogens.

Protein kinase C (PKC) I (gamma), II (beta) and III (alpha) subspecies' activities are inhibited by three triphenylacrylonitrile (TPE) antiestrogens at micromolar concentrations. TPE 1 (having a p-hydroxy and a p-diethylaminoethoxy group on the 3-, and 3'- phenyl rings respectively) and TPE 2 (having a p-diethylaminoethoxy group on both the 3-, and 3'- phenyl rings) are competitive with the mechanism of activation by phosphatidylserine (PS). TPE 3 (having p-hydroxy groups on each of the three phenyl rings) is non-competitive with PS and inhibits the Ca2+- and PS-independent phosphorylation of protamine sulfate by PKC subspecies. This evidence suggests that PKC activity can be inhibited by different routes depending on the TPE structure: diethylaminoethoxy side chain-substituted TPEs (TPE 1 and 2) interact with PS as well as with the regulatory domain, whereas the trihydroxylated derivative (TPE 3) inhibits the enzyme by interacting with the catalytically active site.

Acrylonitrile↗
PubMed1989

Fatal rhabdomyolysis and renal failure associated with hand, foot and mouth disease.

Fatal severe rhabdomyolysis and anuric renal failure developed in a young man who had contracted hand, foot and mouth disease during an epidemic of this disease. Viral studies implicated coxsackievirus A16 as the infecting agent. This appears to be the first reported case of rhabdomyolysis that was associated with hand, foot and mouth disease and infection with coxsackievirus A16.

Adult↗
PubMed1989

Cerebellar [3H]inositol 1,4,5-trisphosphate binding is markedly decreased in human olivopontocerebellar atrophy.

We examined the behaviour of [3H]inositol-1,4,5-trisphosphate (IP3) binding in autopsied cerebellar and cerebral cortex of 10 neurologically normal controls and 8 patients with end-stage olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder characterized histologically by severe degeneration of Purkinje cells. [3H]IP3 binding to normal human cerebellar cortex was 6-15 times higher than in cerebral cortex. As compared with the controls, mean [3H]IP3 binding to cerebellar cortex was markedly reduced by 61% in the OPCA patients whereas levels were normal in frontal and occipital cortices. Since the Purkinje cell dendrite receives neuronal input from granule cells and climbing fibers utilizing glutamate and aspartate, respectively, as neurotransmitters, the reduced IP3 binding in OPCA cerebellar cortex may reflect a loss of Purkinje cells containing these excitatory amino acid receptors linked to the phosphatidylinositide second messenger system. Our data suggest that in humans, IP3 receptors may be highly localized to the Purkinje cell dendrite.

Adult↗
PubMed1989

The outcome index. A method of quality assurance in the special care area.

A method of quality assurance for a surgical intensive care unit is described. A system outcome score is devised, incorporating only easily obtained objective components that reflect the likelihood of death. Through the use of a derived outcome index, the actual mortality rate is compared with the predicted mortality rate as a method of monitoring the quality of care provided. Subroutines exist to identify errors in data entry, to detect malicious interference in patient care, to add nonscoring components for the purposes of clinical studies, and to facilitate retrieval of a concise summary of the major events during the stay of every patient admitted to the intensive care unit.

Abstracting and Indexing↗
PubMed1989

Detection of residues of chloramphenicol in crude extracts of fish and milk by tandem mass spectrometry.

The collision-induced dissociation mass spectrum, observed with a hybrid tandem instrument, of the ammonia chemical ionization protonated molecular ion of chloramphenicol was used for the detection of residues of the drug in biological samples. The extracted oil from fish was subjected to a rapid clean-up on a pre-packed silica gel cartridge prior to non-chromatographic tandem mass spectral analysis. Fat extracted from milk was analysed directly by on-line combined high-performance liquid chromatography/tandem mass spectrometry with rapid elution of chloramphenicol. Identification was on the basis of agreement of the daughter ion spectra obtained from sample extracts with that of the chloramphenicol standard. Detection was unambiguous at 0.5 mg kg-1. The sensitivity advantage normally expected with multiple reaction monitoring was not achieved owing to the effect of neutral noise phenomena.

Animals↗
PubMed1989

Saturation of human chromosome 3 with unique sequence hybridization probes.

We have generated chromosome 3-specific recombinant libraries in both lambda and cosmid cloning vectors starting with somatic cell hybrids (hamster/human) containing either an intact chromosome 3 or a chromosome 3 with an interstitial deletion removing 75% of long-arm sequences. The libraries contained between 2 X 10(5) and 5 X 10(6) independent recombinants. Approximately 2% of the recombinants in these libraries contain inserts of human DNA. These were identified by hybridizing the recombinants to radioactively labeled total human DNA. Over 2500 recombinants containing human DNA were isolated from these various libraries and DNA was prepared from each of them. This represents 80,000 kb of cloned chromosome 3 sequences. One-third of the DNAs were digested with EcoRI or HindIII, and fragments free of repetitive sequences were radioactively labeled using random hexanucleotide primers and tested as unique sequence hybridization probes. Over 6500 of the fragments were tested and of these 758 were unique sequence probes with minimal or no background hybridization. Their hybridization only to chromosome 3 was verified. These probes, which were derived from 452 independent recombinants, should provide an effective saturation of human chromosome 3.

Animals↗
PubMed1989

Effect of triphenylacrylonitrile derivatives on estradiol-receptor binding and on human breast cancer cell growth.

In a study of a series of 26 triphenylacrylonitrile derivatives (TPEs), we investigated the influence of several possibly interrelated factors on the proliferation of human breast cancer cell lines. (1) Chemical substituents: the test compounds were for the most part para-hydroxylated with increasingly bulky hydrophobic and/or basic side chains [isopropyloxy or (diethylamino)ethoxy] or standard reference compounds. (2) Relative binding affinities (RBAs): they competed diversely for [3H]estradiol (E2) binding to calf uterus cytosol and little, if at all, for binding to the [3H]tamoxifen-labeled antiestrogen binding site (AEBS) in lower speed supernatant. A multiparametric comparison of RBAs recorded for calf, rat, and mouse uterus cytosol estrogen receptor (ER) revealed a possible influence of species-specific receptor conformation and/or environment on binding. (3) Estrogen/antiestrogen potency: their stimulation and inhibition of the proliferation of the ER-positive human breast cancer cell line (MCF7) was measured. Compounds with only hydroxy substituents stimulated proliferation more markedly than methylated derivatives and had a maximum effect at 10(-11)-10(-6) M. Stimulation was related to the RBA for ER. Compounds with isopropyloxy or (diethylamino)ethoxy side chains only weakly stimulated MCF7 cell growth and more powerfully antagonized E2-promoted growth. The extent of inhibition depended upon the bulk of the side chain and could be reversed by 10(-7) M E2. Within the same concentration ranges, the test compounds were without effect on the BT20 ER-negative cell line. (4) Cytostatic and/or cytolytic activity: most compounds could arrest the proliferation of both MCF7 and BT20 cells at concentrations above 3 x 10(-6) M. This activity was thus independent of ER. Nevertheless, those compounds with a charged hydrophobic side chain, which were the most powerful antagonists of E2-promoted cell growth, were also the most cytotoxic. The overall results for all molecules on all parameters were submitted to a multivariate analysis (correspondence analysis) which revealed the progressive influence of increasing substitution by hydroxy and more bulky groups on the generation of antagonist activity and cytotoxicity.

Animals↗
PubMed1989

Thoracic paravertebral block: a method of pain control.

The adverse effects of pain on acutely ill or traumatized patients are well documented. A variety of pain-relieving techniques are now available to meet the varied requirements for pain relief. This paper presents the results of a single, large-volume injection of bupivacaine 0.5% in the thoracic paravertebral space, achieving pain relief over several thoracic dermatomes in patients with respiratory compromise secondary to thoracic or upper abdominal injury. The block proved quick and simple to perform, with excellent clinical results of long duration and virtually no complications. Although not previously described, this single, large-volume injection approach to achieving an extensive thoracic paravertebral block may well become an important pain management technique in appropriate patients.

Abdominal Injuries↗
PubMed1989

Down's syndrome individuals begin life with normal levels of brain cholinergic markers.

We measured the activities of the cholinergic marker enzymes choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in autopsied brains of seven infants (age range 3 months to 1 year) with Down's syndrome (DS), a disorder in which virtually all individuals will develop by middle age the neuropathological changes of Alzheimer's disease accompanied by a marked brain cholinergic reduction. When compared with age-matched controls cholinergic enzyme activity was normal in all brain regions of the individuals with infant DS with the exception of above-normal activity in the putamen (ChAT) and the occipital cortex (AChE). Our neurochemical observations suggest that DS individuals begin life with a normal complement of brain cholinergic neurons. This opens the possibility of early therapeutic intervention to prevent the development of brain cholinergic changes in patients with DS.

Acetylcholinesterase↗
PubMed1989

Totally implantable venous access systems in paediatric practice.

Forty seven totally implantable venous access systems have been inserted in 45 patients for the management of malignant disease (n = 29), haematological disorders (n = 5), and cystic fibrosis (n = 11). We report our experience with them and discuss the problems we have encountered during the past three years.

Adolescent↗
PubMed1989

DNA replication and cell cycle control in Xenopus egg extracts.

Aspects of the regulation of DNA replication and mitosis have been studied using a cell-free extract of Xenopus eggs. The extract is characterized by repeated cycles of DNA replication and mitosis, which are accompanied by periodic synthesis and degradation of cyclins as well as fluctuations in the level of Histone H1 kinase activity. DNA replication in this system is dependent upon the formation of a nucleus. However, while nuclear structures are clearly required for initiation, a complete nuclear membrane does not appear to be necessary. Indirect immunofluorescence and DIC microscopy indicate that nuclear reformation from chromosomes occurs asynchronously around individual chromatids. Lamin polymerization, biotin-11-dUTP incorporation and association of polymerases with chromatin occur before membrane formation is complete. S phase nuclei are typified by the co-distribution of both anti-DNA polymerase alpha and anti-PCNA antibodies as discrete spots of fluorescence which align the chromatin. However, as DNA replication is terminated, PCNA fluorescence fades and DNA polymerase alpha dissociates from the chromatin and is redistributed throughout the nucleoplasm. By inhibiting DNA replication with aphidicolin, both DNA polymerase alpha and PCNA remain associated with the chromatin throughout prolonged incubation. Under these conditions mitosis is delayed by up to 70 min, although both the general rate of protein synthesis and more importantly the rate of cyclin synthesis and histone kinase activation are unaffected. Upon nuclear envelope breakdown and lamin dispersal, cyclins degrade; however, no chromosomes are formed, and both PCNA and DNA polymerase alpha remain associated with the chromatin. Also, histone kinase activity is maintained at elevated levels.

Animals↗