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Biomedical subjects

L Wilson

Publications and source records attributed to L Wilson.

At least 487 records · Page 27Linked to original sources
PubMed1967

The interaction of alpha-chymotrypsin with isosteric substrates of different charge type.

1. The synthesis of three substrates of alpha-chymotrypsin of closely similar steric requirements but different charge type is reported. 2. The interaction of these compounds [SS-dimethyl-(l-3-carboxymethyl-3-acetamido)propyl sulphonium iodide, l-2-acetamido-5-methylhexanoic acid methyl ester and N-acetyl-l-glutamic acid alpha-methyl ester] with alpha-chymotrypsin has been studied. 3. For the charged substrates, values of k(0) are two orders of magnitude smaller than, and values of K(m) two orders of magnitude larger than, the corresponding values for the uncharged isostere. 4. The results are interpreted in terms of the known specificity of the enzyme, and the relationship between binding and kinetic specificities is discussed.

Binding Sites↗
PubMed1966

The combined effects of ethanol and amphetamine sulfate on performance of human subjects.

The combined effects of ethanol and amphetamine on the performance of selected tests were evaluated. No differences were shown between the effects of ethanol-amphetamine and ethanol-lactose on the performance of balance, skipping, Minnesota manipulation, Purdue peg board, Maudsley Personality Inventory, pursuit rotor or digit span tests; but ethanol plus amphetamine produced less impairment of performance of coding, mental addition, and trail making tests than did ethanol plus a placebo. Ethanol increased the errors in performance of the Wonderlic Personnel Test, but the simultaneous administration of amphetamine did not reduce this effect. Conversely, amphetamine reduced the test-retest reliability of the Wonderlic Personnel Test, but alcohol appeared to counteract this effect of amphetamine. These experiments indicate that, when ethanol and amphetamine are used together, each drug modifies some of the effects produced by the other in a manner that cannot be predicted on the assumption that a depressant versus stimulant competition is operative.

Adult↗
PubMed1966

Water soluble products of UV-irradiated autoxidized linoleic and linolenic acids.

The water-soluble products of the UV-initiated autoxidation of linoleic and linolenic acids emulsified in water were separated into volatile and relatively involatile components, each of which reacted with both thiobarbituric acid (TBA) and peroxidase. The volatile TBA-reactive compound is probably malonaldehyde and the volatile peroxidase-reactive compound is hydrogen peroxide. Additional compounds which absorb UV light were present in the volatile fraction. After thin-layer chromatography of the involatile fraction, reactivity toward TBA and peroxidase was found in the same spot. Approximate molar yields of hydrogen peroxide, malonaldehyde, "hydroperoxides", and other TBA-reactive compounds were estimated. The ratio of "hydroperoxide" to TBA reactivity was lower for linoleic than for linolenic acid. The mass of relatively involatile compounds was about 20 times greater than that predicted from either peroxidase or TBA assays of water extracts of oxidized linolenic acid. The properties of the water extract were similar to those shown by others for the products of prolonged autoxidation (without UV-irradiation) of emulsified methyl linoleate.

Barbiturates↗
PubMed1966

Water-soluble inhibitor(s) of tumor respiration formed from ultraviolet-induced oxidation of linoleic and linolenic acids.

Inhibition of Ehrlich ascites carcinoma respiration by aqueous extracts of oxidized linoleic or linolenic acid (aqueous emulsions UV-irradiated, 90 min) was associated entirely with relatively involatile compounds which were both thiobarbituric acid (TBA)-reactive and peroxidase-reactive. Inhibitory compounds were heat stable and migrated in thin-layer chromatography with aldehydes, "hydroperoxides," and TBA-reactive compounds. Peroxidase-catalyzed reduction of the "hydroperoxide" diminished the inhibition. At 4.7 x 10(-5) M "hydroperoxide" concentration, the residues from both linoleic and linolenic acid inhibited tumor oxygen consumption to a similar degree. However, at this concentration of "hydroperoxide" only the dried extract from linolenic acid was able to produce inhibition (100%) of aerobic glucose utilization by tumor cells. No glycolytic inhibition by the dried residue of oxidized linoleic acid was observed. At least 12 compounds (approximate chain length, 7C-13C) containing alpha,Beta-unsaturated carbonyl groups were isolated by gas-liquid chromatography (GLC) of dried extracts of oxidized linolenic acid. No single fraction inhibited tumor respiration, but the recombined mixture of all compounds caused complete respiratory inhibition of ascites tumor cells. Less material was required to inhibit oxygen consumption before than after GLC presumably because the more highly inhibitory components of the extract (along with "hydroperoxides" and TBA-reactive compounds) were lost during GLC. Extracts from oxidized linolenic acid were found to produce in all tumor cells cytoplasmic evaginations which were readily detected by phase microscopy.

Animals↗
PubMed1965

Psychiatric concepts.

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Education, Nursing, Continuing↗
PubMedDate not supplied

A gene therapy/targeted radiotherapy strategy for radiation cell kill by.

BACKGROUND: Although [131I]meta-iodobenzylguanidine (MIBG) is currently one of the best agents available for targeted radiotherapy, its use is confined to a few neural crest derived tumours which accumulate the radiopharmaceutical via the noradrenaline transporter (NAT). To determine whether this drug could be used for the treatment of non-NAT expressing tumours following genetic manipulation, we previously showed that plasmid mediated transfection of NAT into a non-NAT expressing glioblastoma cell line, UVW, endowed the host cells with the capacity to actively accumulate [131I]MIBG. We now present data defining the conditions required for complete sterilisation of NAT transfected cells cultured as multicellular spheroids and treated with [131I]MIBG. METHODS: NAT transfected UVW cells, grown as monolayers and spheroids, were treated with various doses of [131I]MIBG and assessed for cell kill by clonogenic survival and measurement of spheroid volume over time (growth delay). Spheroids were left intact for different time periods to assess the effect of radiation crossfire on cell death. RESULTS AND CONCLUSIONS: Total clonogen sterilisation was observed when the cells were grown as three-dimensional spheroids and treated with 7 MBq/ml [131I]MIBG. The added benefit of radiation crossfire was demonstrated by the improvement in cell kill achieved by prolongation of the maintenance of [131I]MIBG treated spheroids in their three-dimensional form, before disaggregation and clonogenic assay. When left intact for 48 h after treatment, spheroid cure was achieved by exposure to 6 MBq/ml [131I]MIBG. These results demonstrate that the efficiency of cell kill by [131I]MIBG targeted therapy is strongly dependent on beta-particle crossfire irradiation. This gene therapy/targeted radiotherapy strategy has potential for [131I]MIBG mediated cell kill in tumours other than those derived from the neural crest.

3-Iodobenzylguanidine↗
PubMedDate not supplied

Evidence for a role of cyclooxygenase (prostaglandin synthetase) and prostaglandins in the sperm acrosome reaction and fertilization.

Three cyclooxygenase (prostaglandin synthetase) inhibitors, indomethacin, phenylbutazone, and oxyphenbutazone, decreased fertilization in vitro when mixed with capacitated mouse spermatozoa before addition of the treated gametes to oocytes. Fertilization was inhibited whether the oocytes were intact, follicle cell-free, or both follicle cell-free and zona-free. At various concentrations of inhibitor, no effect was observed on the motility or forward progression of the spermatozoa. These cyclooxygenase inhibitors also decreased the guinea pig acrosome reaction. Inhibition of the acrosome reaction did not occur when a mixture of the prostaglandins (PGE2 or PGF2 alpha) and one of the inhibitors was added to the spermatozoa. Alone, these prostaglandins tended to enhance the rate at which the acrosome reaction took place. Lowered calcium levels reduced the occurrence of the acrosome reaction, an effect that could be reversed at least partially by the addition of PGE2. Even in the nominal absence of calcium, some acrosome reaction took place when PGE2 was present in the medium. These results support an essential role for cyclooxygenase and arachidonic acid metabolites, including prostaglandins, in the events leading to the acrosome reaction and fertilization.

Acrosome↗
PubMedDate not supplied

A survey for antibodies to Lassa virus among health workers in Nigeria.

A study was conducted among 552 health workers at 6 health facilities in Nigeria. Lassa virus immunoglobulin (Ig) G antibody was detected in 12.3%, using an enzyme-linked immunosorbent assay. Antibody prevalence in the 6 health centres ranged from 1.2% to 27.3%. Prevalences were higher in primary and secondary health facilities than in tertiary centres. Seroprevalences ranged from 1.7% to 23.7% among different occupational groups of health workers; the highest observed antibody prevalence was among ward aids. Lassa virus IgM antibody, indicating recent infection, was present in 6 of the health workers, 5 of whom were ward aids and one was a nurse. All of the health workers with specific IgM came from a single facility in Lafia, sampled during an outbreak of Lassa fever.

Antibodies, Viral↗
PubMedDate not supplied

Comparison of the in vivo activity of different oxytocin antagonists in the pregnant baboon.

OBJECTIVE: To ascertain the relative activity of five oxytocin antagonists (OTAs) in vivo in a tethered pregnant baboon model and compare these results to previously reported affinities in human and rat oxytocin receptor assays and median effective dose in rat uterotonic bioassays. METHODS: Pregnant tethered baboons between days 130 and 160 of pregnancy were given an oxytocin challenge test 1 minute after infusion of 1 mg of one of five randomly selected OTAs: ANTAG I, ANTAG II, ANTAG III, L366948, and Atosiban. Once the uterine response to oxytocin returned to normal (1-8 days) the OCT was repeated with one of the remaining, untested OTAs during the 130-160 day period. Uterine activity, the time until the first significant response, and the dose of oxytocin needed to induce this response were all factored into one expression, the antagonist-response interval (ARI). RESULTS: When expressed as ratio to ANTAG I the relative ARI for the OTAs were 0, .5, 1.0, 2.4 and 59.2 for L366948, Atosiban, ANTAG I, ANTAG II, and ANTAG III, respectively. ANTAG III and L366948 were significantly different from each other and the three other OTAs (P < .05). The log10 ARI for the 4 active OTAs when correlated with the log10 of the human and rat oxytocin receptor affinities and the rat uterotonic bioassay were all highly correlated (r = .99; P < .05). CONCLUSION: ANTAG III is a potent, long-acting OTA in vivo in the pregnant baboon and has the potential as a tocolytic in humans.

Animals↗
PubMedDate not supplied

Efferent and afferent connections of mouse sensory-motor cortex following cholinergic deafferentation at birth.

The present study investigates the effect of cholinergic basal forebrain lesions at birth on cortical connectivity in adulthood. We have previously shown that such neonatal lesions result in extensive cortical cholinergic deafferentation during early postnatal development, which is accompanied by abnormal morphogenesis of cortical cytoarchitecture (Höhmann at al., 1988). Here, we have used WGA-HRP to label anterogradely and retrogradely afferent and efferent projections of dorsal neocortex. Our results show an altered projection pattern from dorsal thalamus to layer IV of sensory-motor cortex following lesions among the cholinergic basal forebrain neurons (nBM), while corticothalamic projections from layer VI appear normal. In addition, corticofugal projections from layer V, labeled by striatal injection, appear to be expanded following the lesion. This indicates that cortical layers undergoing differentiation after the newborn nBM lesion present with long-term abnormalities in connectivity. The present results are compatible with the hypothesis that cholinergic afferents are instrumental in the regulation of cortical morphogenesis. Furthermore, our data show that ontogenetic disturbances can lead to structural abnormalities that persist long after the initial deficiency has abated. We discuss the significance of these results in relationship to human neurological disorders.

Afferent Pathways↗
PubMedDate not supplied

A simple, reliable method for the determination of chlorinated volatile organics in human breath and air using glass sampling tubes.

A method for determining chloroform, 1,1,1-trichloroethane, carbon tetrachloride, and trichloroethene in breath samples was developed. It consisted of collecting samples in 40-ml. glass-silanized tubes that were 16-in. long and had a 0.64-in. diameter. The ends tapered, resulting in a tube with a 1/4-in. diameter that was 1 3/4-in. long; each end had a shutoff valve attached. One end had a strip of rubber tube attached to the shutoff valve for collecting the breath sample, and the other end contained a 1/4-in. Swagelok nut with a rubber septum for withdrawing the sample. Samples were withdrawn using a pressure-lock, gastight syringe, and they were injected onto a gas chromatograph fitted with an electron-capture detector. The analytes were stable for at least 22 days in these tubes. The method detection limit was determined to be 0.03, 0.08, 0.04, and 0.04 pg/ml. for chloroform, 1,1,1-trichloroethane, carbon tetrachloride, and trichloroethene, respectively. Precision, based on 13 injections, was determined to be 13% for 0.09 pg chloroform, 13% for 0.21 pg 1,1,1-trichloroethane, 8% for 0.16 pg carbon tetrachloride, and 14% for 0.1 pg trichloroethene. In all, the proposed method is a sensitive and reliable one for determining volatile organic compounds in breath and a method that can also be applied to air sampling.

Air Pollutants↗