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K Cooper

Publications and source records attributed to K Cooper.

At least 19 recordsLinked to original sources
PubMed1992

1,4-Dihydropyridines as antagonists of platelet activating factor. 1. Synthesis and structure-activity relationships of 2-(4-heterocyclyl)phenyl derivatives.

A novel class of 2-(4-heterocyclylphenyl)-1,4-dihydropyridines (2-38) possessing antagonist activity against platelet activating factor (PAF) was prepared by the Hantzsch synthesis from a variety of ethyl 4'-heterocyclic-substituted benzoylacetates, aryl or heteroaryl aldehydes, and substituted 3-aminocrotonamides or 3-aminocrotonate esters. Structure-activity relationships were evaluated where PAF antagonist activity was measured in vitro by determining the concentration of compound (IC50) required to inhibit the PAF-induced aggregation of rabbit washed platelets, and in vivo by determining the oral dose (ED50) which protected mice from a lethal injection of PAF. The nature of the substituent at the dihydropyridine 2-position was found to be important for both in vitro and in vivo activity, whereas there was greater flexibility for structural variation at the 4- and 5-positions. The most potent compound was 4-(2-chlorophenyl)-1,4-dihydro-3-(ethoxycarbonyl)-6-methyl-2-[4-(2- methylimidazo[4,5-c]pyrid-1-yl)phenyl]-5-[N-(2- pyridyl)carbamoyl]pyridine (17, UK-74,505), IC50 = 4.3 nM, ED50 = 0.26 mg/kg po, which was found to be approximately 33 times more potent in vitro (rabbit platelet aggregation) and about 8 times more potent in vivo (murine lethality) than WEB2086. Compound 17 also exhibited a long duration of action in the dog (inhibition of PAF-induced whole blood aggregation ex vivo was maintained for greater than 24 h following a single oral dose of 75 micrograms/kg) and was highly selective as a PAF antagonist, showing only weak affinity (IC50 = 6600 nM) for the [3H]nitrendipine binding site. As a result of its high oral potency, selectivity, and duration of action, UK-74,505 has been selected for clinical evaluation.

Animals↗
PubMed1992

Transient outwardly rectifying potassium channel in the rabbit corneal endothelium.

Ionic currents from freshly dissociated rabbit corneal endothelial cells were examined using patch-clamp technology and a perforated patch technique. Whole-cell current recordings revealed a transient outward K(+)-selective current that was blockable in a dose-dependent manner by 4-aminopyridine (4-AP) and quinidine. This current is similar to the 'A'-type current present in many excitable cells and is the first reported instance of such a current in any epithelial cell type. In addition to the transient current, an outwardly rectifying nonselective cation current was also observed. This current is also blocked by quinidine. To examine the possible role of these currents in the stromal volume regulatory function of the endothelium, corneas were perfused under a specular microscope with a glutathione-bicarbonate Ringer's solution (GBR) or GBR plus either 1 mM quinidine or 10 mM 4-AP. For quinidine perfusions, control corneas swelled at a rate of 6 microns/hr, while quinidine-perfused corneas swelled at a rate of 48 microns/hr. For 4-AP perfusions, control corneas swelled at a rate of -2 microns/hr, while 4-AP perfused corneas swelled at a rate of 24 microns/hr. One possible mechanism of the stromal swelling induced by these K+ channel blockers may be the result of loss of the K+ recycling pathway necessary for proper Na+/K+ ATPase function.

Animals↗
PubMed1992

Potassium currents from isolated frog lens epithelial cells.

Using the perforated patch version of whole-cell recording, we have measured currents from isolated frog lens epithelial cells. Three types of currents were seen. A time-independent outwardly rectifying potassium current was identified that sets the resting voltage. This potassium current differs significantly from any of the potassium currents recorded with the whole-cell technique in mammalian lens epithelial cells. In addition to the potassium current, the two other currents present were both outwardly rectifying: one was time-independent while the other showed distinct activation.

Animals↗
PubMed1992

Divalent cation effects on lens conductance and stretch-activated cation channels.

In patch clamp studies of apical membrane from frog lens epithelium, the most frequently observed channel is 'stretch-activated', highly selective for cations over anions but showing little selectivity for Na+ vs. K+. In normal physiological saline, the open channel conductance is 25-30 pS and quite linear over +/- 100 mV. In the absence of extracellular divalent ions, the open channel conductance for inward current flow increases to about 50 pS at the normal lens resting voltage of -75 mV, whereas the conductance for outward current flow is unaffected. In the intact lens, removal of extracellular divalents causes the input conductance approximately to double and the intracellular voltage to depolarize from -74 to -58 mV. A variety of divalent ions block this change in whole lens conductance and voltage in the same order in which they block the 'stretch channels'. Single voltage-clamped epithelial cells also increase their conductance when Ca2+ is removed from their bathing medium. There are, therefore, some striking parallels between the open channel properties of the 'stretch-activated' cation channel and the response of the whole lens or single lens cells to removal of extracellular Ca2+. There are also inconsistencies. This channel is apparently not open in the normal resting lens so removal of extracellular Ca2+ must cause it to open if it is indeed responsible for the increase in lens conductance. However, we have not been able to demonstrate convincingly an increase in open probability at the single-channel level when external divalents are removed.

Animals↗
PubMed1992

Exposure assessment for heavy metal ingestion from a sport fish in Puerto Rico: estimating risk for local fishermen.

Sport or subsistence fishermen sometimes underestimate the risks from eating local fish and distrust authorities regarding potential hazards from fish. We report on lead, cadmium, selenium, and mercury levels in snook, locally called robalo (Centropomus spp.), consumed by local fishermen in Puerto Rico, who ate up to 23 fish/wk. Median levels (in ppb, dry weight) for muscle, adipose, and liver ranged from 683 to 780 for lead, 37 to 600 for cadmium, 50 to 146 for mercury, and 361 to 3986 for selenium. Lead levels were similar in all tissues, and selenium and cadmium levels were highest in the liver. Mercury was higher in muscle than in liver. Computing exposure via ingestion for the average fisherman indicated that if one were to consume robalo throughout the year one would be exposed in excess of the EPA Reference Dose (RfD) for mercury. Using a widely accepted maximum consumption of 200 g/d for fishermen yielded hazard indices (daily consumption/RfD) below 1 for all four metals, with a value approaching 1 for mercury in adults, and over 1 for 16-kg children. The possibility that in certain localities and cultures sport or subsistence fishermen may consume fish at levels substantially above 200 g/d should be investigated in performing risk assessments, particularly outside the continental United States.

Adipose Tissue↗
PubMed1992

Randomised comparative study in 217 women of three disposable plastic IUCD thread retrievers.

OBJECTIVE: To assess the relative efficacy of three disposable plastic instruments in the retrieval of 'missing' IUCD threads. DESIGN: A prospective randomised comparative single centre study. SETTING: Family Planning Clinic in London, UK. SUBJECTS: 217 of 350 IUCD users referred to the research team with 'missing' IUCD threads entered the study. INTERVENTION: All women initially underwent exploration of the endocervical canal with Spencer Wells forceps. When this procedure did not retrieve the threads, the patients were entered into the study. A maximum of two randomly chosen plastic IUCD thread retrievers were then used in any one patient to explore the uterine cavity and capture the 'missing' threads. The order in which the two retrievers were employed was also determined at random. Four separate entries into the uterine cavity were permitted with each instrument, the endocervical canal being explored with Spencer Wells forceps after each retraction of the instrument to identify the possible descent of the threads. MAIN OUTCOME MEASURES: Threads brought down beyond the external cervical os, or threads brought to within the endocervical canal and then grasped by Spencer Wells forceps. RESULTS: In approximately 40% of all patients, the threads were retrieved with Spencer Wells forceps alone and a further 40% with the disposable plastic retrievers. About 5% had no retrievable threads, and only 2.5% of the referred patients required general anaesthesia for removal of their IUCD. The analysis of the comparative trial was confined to the 197 patients with retrievable threads which could not be brought below the external os with Spencer Wells forceps. The first plastic retriever used was successful in 50% of patients. The Retrievette (59%) and the Emmett (53%) performed better than the Mi-Mark Helix (37%) in this study. The difference was statistically significant (P = 0.03) and the 95% confidence interval for the difference of the Mi-Mark Helix from the other two retrievers was 4% to 33%. This retrieval rate for the Mi-Mark Helix was much worse than in previously reported studies, though one doctor did have a better success rate with this retriever. The success rates, using a second plastic retriever randomly chosen from the two not used in the first attempt, were almost identical to those observed with the first retrievers: 63%, 56% and 36%. The success rate did not appear to be influenced by the length of thread, day of cycle, device type or parity. The success of the second retriever tried did not seem to be influenced by the retriever that had failed previously. CONCLUSIONS: Based on our experience, the initial exploration of the endocervical canal with Spencer Wells forceps is invaluable. If this simple manoeuvre fails to retrieve the 'missing' threads, either the Retrievette or the Emmett thread retrievers are useful tools in general practice or in the family planning clinic setting.

Female↗
PubMed1992

Detection of human papillomavirus in matched cervical smears and biopsy specimens by non-isotopic in situ hybridisation.

AIMS: To determine the relative diagnostic sensitivity of non-isotopic in situ hybridisation (NISH) for the diagnosis of human papillomavirus (HPV) on matched smears and biopsy specimens; to compare the NISH signal type in the two samples; and to correlate the NISH data with the morphological diagnosis. METHODS: HPV samples were assayed individually by NISH with digoxigenin labelled probes (HPV6, 11, 16, 18, and 33) on routinely collected paraffin wax embedded cervical biopsy specimens and for high risk HPVs with a cocktail of similarly labelled probes (HPV16, 18, 33) on matched smears. These were taken at the same colposcopic examination from 32 patients investigated for an abnormal cervical Papanicolaou (PAP) stained smear. RESULTS: An HPV signal was present in 18 (56%) biopsy specimens and in 14 (44%) smears. There was higher concordance of sets of data in the presence of cytopathic wart virus changes. The superiority of biopsy over smear in detecting HPV was mainly the result of examining the entire cervical biopsy specimen rather than cells scraped from the cervical surface. The NISH signal type in both biopsy specimen and smear was similar; it has been shown that NISH type 1 signal correlates with episomal viral replication and type 2 and 3 signals with viral integration. CONCLUSIONS: These data show that NISH on cervical smears is a worthwhile primary screen for HPV infection. The NISH signal types in cervical smears are similar to those previously described in cervical biopsy specimens.

Biopsy↗
PubMed1992

Integration of human papillomavirus types 16 and 18 in cervical adenocarcinoma.

AIMS: To determine which type of human papillomavirus (HPV) is associated with cervical adenocarcinoma and whether the virus was integrated or episomal in two continents. METHODS: Biopsy specimens from the UK (n = 16) and South Africa (n = 22) were analysed by non-isotopic in situ hybridisation (NISH) for HPV types 6, 11, 16, 18, 31, 33, and 35 on archival biopsy specimens using digoxigenin labelled probes. RESULTS: A total of 20 adenocarcinomas (53%) from both groups contained HPV DNA. In the UK group, seven and four cases contained HPV 18 (44%) and 16 (25%) respectively. In the South African group, nine cases contained HPV 18 (41%) while HPV DNA was not detectable in the other 13 cases. Hence HPV 18 was present in 80% of HPV positive adenocarcinomas. CONCLUSIONS: The HPV 16 or 18 genome was integrated in all viral positive cases. In two cases HPV 18 was also present in an episomal form. These data indicate that HPV integration is common to cervical adenocarcinoma in two continents by the same methodology. The lower prevalence of HPV 18 detection in the South African group may have been due to the presence of other or unsequenced HPV types.

Adenocarcinoma↗
PubMed1991

Lymphomatoid granulomatosis. A report of 4 cases.

Only 1 case of lymphomatoid granulomatosis has previously been reported from South Africa. Experience with 4 such adult patients (2 blacks and 2 whites) is described. These patients were followed up for 15-48 months and none developed evidence of a lymphoma during this period. Fever, weight loss, cough and breathlessness were prominent symptoms in all patients. One patient, a black woman, with a diffuse interstitial pattern of lung involvement, had digital clubbing--a rare accompaniment that resolved after therapy. Dilated congestive cardiomyopathy was found in association with pulmonary nodules in a black male patient. All 4 patients were treated with cytotoxic regimens. The 2 patients treated with oral cyclophosphamide and prednisolone responded favourably. The possible explanation for paucity of reports of lymphomatoid granulomatosis from South Africa could be under-reporting, underdiagnosis or a true geographic/ethnic variation in the incidence of this condition.

Adult↗
PubMed1991

Sodium channels in ocular epithelia.

Voltage-gated, tetrodotoxin(TTX)-blockable sodium channels are found in most excitable cells and are the primary contributors to action potentials generated by many of these cells. To date, there has only been one report of a non-cultured vertebrate epithelial cell type containing TTX-blockable Na+ channels: rabbit non-pigmented ciliary body epithelial cells [Cilluffo MC et al. (1991) Invest Opthalmol Vis Sci 32: 1619-1629], and three reports of cultured epithelial cells containing TTX-blockable Na+ channels: rabbit non-pigmented and pigmented ciliary body epithelium [Ciluffo MC et al. (1991) Invest Opthalmol Vis Sci 32: 1619-1629; Fain GL, Farahbakhsh (1989) J Physiol (Lond) 417: 83-103] and human lens epithelium [Cooper K et al. (1990) J Membr Biol 117: 285-298]. We report here the presence of sodium currents in two different non-cultured, freshly dissociated transporting epithelial cell types: the rabbit corneal endothelium and the frog lens epithelium. We also report the occurrence of sodium currents in six additional cultured ocular epithelial cell types from three different species. These currents have a current/voltage (I/V) relationship consistent with traditional voltage-gated Na+ currents, are quinidine- and TTX-blockable (of the low-affinity TTX-sensitive type), and disappear following bath substitution of Na+ with Cs+ or K+.

Animals↗
PubMed1991

Low access resistance perforated patch recordings using amphotericin B.

We present experimental procedures describing the creation of perforated patches by use of amphotericin B. In 13 different cellular preparations, access resistances below 10 M omega were achieved and with blunt electrode tips, access resistances of 3-4 M omega were possible. In addition to using the techniques to measure whole cell currents, we have used them to measure single channel currents in a new "outside-out patch" preparation and we have utilized them to measure the resting voltage of epithelial monolayers. We conclude that these new approaches can provide a substantial increase in versatility and quality for many kinds of electrophysiological measurements.

Amphotericin B↗
PubMed1991

The serological responses of chickens to mass vaccination with a live V4 Newcastle disease virus vaccine in the field and in the laboratory. 1. Meat chickens.

Meat chickens on commercial broiler farms were vaccinated once at 1 to 15 days of age with a live V4 Newcastle disease virus (NDV) vaccine administered by drinking water, aerosol or coarse spray. Hatchmates were housed and similarly vaccinated in laboratory isolation pens. Samples of birds were bled at weekly to fortnightly intervals and the serums tested for haemagglutination inhibiting antibody to NDV. Log2 mean titres of up to 6.26, and assumed protection levels (based on the percentage of birds with log2 titres of 4 or greater) of up to 89%, were obtained in field trials within 4 weeks of vaccination. Differences were observed between the results obtained from parallel field and laboratory trials. The presence of maternal NDV antibody reduced the response to vaccination. The results show that this V4 vaccine can produce an adequate serological response following mass administration to Australian meat chickens housed under commercial conditions.

Aerosols↗
PubMed1991

The serological responses of chickens to mass vaccination with a live V4 Newcastle disease virus vaccine in the field and in the laboratory. 2. Layer pullets.

Layer chickens on a commercial started pullet farm were vaccinated once at 31 to 52 days of age by drinking water or aerosol with live V4 Newcastle disease virus (NDV) vaccine. Flockmates which had been rehoused in laboratory isolation pens shortly beforehand were similarly vaccinated. Samples of birds were bled at intervals and the serums tested for haemagglutination inhibiting antibody to NDV. Log2 mean titres of up to 4.88 and assumed protection levels (based on the percentage of birds with log2 titres of 4 or greater) of up to 81%, were obtained in the field trials within 4 weeks of vaccination. A subsequent laboratory trial further compared the response of different breeds of chicken to different routes of vaccination. Differences were observed between breeds, routes of vaccination, and parallel field and laboratory trials. The results show that this V4 vaccine can produce an adequate serological response following mass vaccination of Australian layer pullets housed under commercial conditions, and that care should be exercised in extrapolating results obtained under laboratory conditions.

Aerosols↗
PubMed1991

Episomal and integrated human papillomavirus in cervical neoplasia shown by non-isotopic in situ hybridisation.

It was postulated that non-isotopic in situ hybridisation (NISH) signal types 1-3 for human papillomavirus in cervical biopsy specimens represent episomal or integrated virus. The aim of this study was to validate this hypothesis by independent molecular techniques. Fresh cervical intraepithelial neoplasia (CIN) and squamous cell cancer (SCC) tissue were examined for NISH signal pattern by hybridising with digoxigenin labelled HPV 16. DNA was extracted from the same samples and analysed by restriction endonuclease digestion and Southern blotting to determine the physical state of the viral genome. Six CIN biopsy specimens showed a type 1 NISH signal for HPV 16. On Southern analysis these biopsy specimens contained only episomal HPV 16. Three SCC with a type 2 NISH signal contained integrated HPV 16 by Southern analysis. Two specimens, a CIN 3 and an SCC with a type 3 NISH signal for HPV 16, showed the presence of both episomal and integrated HPV 16 with conventional Southern analysis and two dimensional gel electrophoresis. These results show that episomal HPV can be reliably determined by NISH type 1 signal, integrated HPV by type 2, and a combination of both episomal and integrated HPV, by a type 3 signal in archival paraffin wax embedded cervical biopsy specimens. This will add another variable to the epidemiological studies of HPV infection. In particular, it will now allow retrospective studies to be done to define the role of episomal and integrated HPV in the evolution of cervical intraepithelial neoplasia and other cervical disease associated with this virus.

Blotting, Southern↗