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K Manning

Publications and source records attributed to K Manning.

At least 37 records · Page 2Linked to original sources

Interferon-alpha (IFN alpha) induces a cytolytic mechanism in ovarian carcinoma cells through a protein kinase C-dependent pathway.

We have recently shown that IFN alpha induces a cytolytic mechanism in human ovarian carcinoma cell lines which is revealed when protein synthesis is subsequently inhibited. In order to determine whether the cytolytic activity induced by IFN alpha was activated through a pathway involving the activation of PKC, the human ovarian carcinoma cell line Caov-3 was exposed to phorbol 12-myristate 13-acetate (PMA). Under conditions where PMA activates PKC, PMA mimicked IFN alpha in its ability to induce a cytolytic mechanism. In contrast, under conditions where PMA depletes PKC, PMA not only did not induce cytolytic activity, but it prevented IFN alpha from inducing cytolytic activity. To further investigate the involvement of PKC in the signaling of cytolytic activity by IFN alpha, the ability of the protein kinase inhibitors, staurosporine, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H7), N-[2-(methylamino) ethyl]-5-isoquinolinesulfonamide dihydrochloride (H8), and N-(2-guanidinoethyl)-5-isoquinolinesulfonamide dihydrochloride (HA1004) to block the induction of cytolytic activity by IFN alpha was determined. The fact that H7, H8, and staurosporine, but not HA1004, blocked the induction of cytolytic activity by IFN alpha provides additional evidence of the involvement of PKC in this activity. Taken together these results indicate that the cytolytic activity induced by IFN alpha is induced through apathway that involves the activation of PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Methylphenidate and seizure frequency in brain injured patients with seizure disorders.

BACKGROUND: Psychostimulant drugs such as methylphenidate are increasingly being used in patients with traumatic brain injury or other brain injuries for a variety of cognitive and behavioral problems. However, there is some reluctance among clinicians and family members to use methylphenidate in brain injured patients because of warnings of seizure occurrence, which are prominently reported by the product labeling included in the Physicians' Desk Reference. METHOD: We retrospectively studied the use of methylphenidate in 30 consecutive patients with active seizure disorders. We compared the seizure frequency in the 3 months before and after methylphenidate with the seizure frequency during methylphenidate treatment, using the Wilcoxon signed-rank test. RESULTS: Overall, the findings demonstrated a trend toward a lesser incidence of seizures in patients during methylphenidate treatment. Only 4 patients had greater seizure frequency during methylphenidate treatment, and 3 of these 4 were receiving tricyclic antidepressants. CONCLUSION: Methylphenidate can be safely used in brain injured patients, even those at high risk for seizures, as it was associated with a trend toward reduction (rather than increase) in seizure frequency in this population.

Adult↗

Isolation of nucleic acids from plants by differential solvent precipitation.

The purification of nucleic acids from plant tissue is often made difficult by the presence of contaminating carbohydrate polymers and polyphenols. A procedure for the simultaneous isolation of DNA and translatable RNA from plants is described. The method removes most of the polysaccharides and polyphenols extracted with nucleic acids in a single step by taking advantage of differences in solubility of these compounds in the solvent 2-butoxyethanol. Stepwise addition of 2-butoxyethanol to phenol extracts of specific ionic strength precipitates nucleic acids largely free of contaminants. Subsequent separation of RNA from DNA by precipitation with LiCl was optimised to give a high recovery of translationally active RNA. Successful isolation of nucleic acids from strawberry (Fragaria X ananassa) receptacle, a particularly recalcitrant tissue, and from a range of tissues of other plant species demonstrates the general applicability of the method.

1-Propanol↗

Heterologous enzyme immunoassay for the determination of free indole-3-acetic acid (IAA) using antibodies against ring-linked IAA.

A solid phase indirect enzyme immunoassay method for the plant growth substance indole-3-acetic acid (IAA) using polyclonal antibodies raised to IAA linked to rabbit serum albumin (RSA) is described. The sensitivity for IAA increased by more than three orders of magnitude as the number of IAA ligands on the coating antigen decreased. Further improvements in assay sensitivity were limited by the high affinity of the antibodies for the bridge group in the IAA conjugate. Substitution of the IAA in the coating antigen by either indole-3-propionic acid or indole-3-lactic acid reduced antibody recognition of the bridge group. The resulting heterologous assay compares favourably with existing homologous immunoassays for IAA in terms of sensitivity and specificity.

Animals↗

A cell culture model of the blood-brain barrier.

Endothelial cells that make up brain capillaries and constitute the blood-brain barrier become different from peripheral endothelial cells in response to inductive factors found in the nervous system. We have established a cell culture model of the blood-brain barrier by treating brain endothelial cells with a combination of astrocyte-conditioned medium and agents that elevate intracellular cAMP. These cells form high resistance tight junctions and exhibit low rates of paracellular leakage and fluid-phase endocytosis. They also undergo a dramatic structural reorganization as they form tight junctions. Results from these studies suggest modes of manipulating the permeability of the blood-brain barrier, potentially providing the basis for increasing the penetration of drugs into the central nervous system.

Animals↗

Criteria audit of percutaneous nephrolithotomies.

A criteria audit of percutaneous nephrolithotomy management is reported. One hundred consecutive patients who underwent percutaneous stone removal over a 3-year period were examined. An analysis of the cases of this relatively new surgical procedure are presented. The audit demonstrated the surgeons' learning curve, the current standards achieved and changes in patient admission rate. Criteria auditing was used and assessed as a quality assurance activity.

Adolescent↗

Detoxification of cyanide by plants and hormone action.

In higher plants cyanide is a co-product of ethylene synthesis. The increase in ethylene production that occurs during the senescence of certain flowers and the ripening of climacteric fruit is accompanied by a rise in beta-cyanoalanine synthase activity. Although these events correlate temporally and spatially, the potential for cyanide detoxification in these tissues is high compared with the expected rate of cyanide formation from the ethylene pathway. However, in stigmas and styles of Petunia flowers a semi-quantitative relationship exists between the activity of beta-cyanoalanine synthase and the activity of ACC (1-aminocyclopropane-1-carboxylic acid) oxidase, the last enzyme in the ethylene pathway. To account for these observations it is proposed that ACC oxidase can react with other amino acids by a general mechanism that liberates cyanide. This hypothesis could also account for the substrate stereospecificity of ACC oxidase, for the extreme lability of this enzyme and for the high accumulation of asparagine in some tissues.

Amino Acid Oxidoreductases↗

Computerized home telemetry of maternal blood pressure in hypertensive pregnancy.

We have developed a telemetric technique whereby maternal blood pressure, which is self-measured by pregnant women in their own homes using a Dinamap 1846 automated blood pressure recorder, can then be transmitted over the commercial telephone network into the Rosie Maternity Hospital in Cambridge, where it is computer-processed. The maternal blood pressure is then reviewed by the obstetrician as part of the clinical management protocol. We have used this telemetric technique on 90 occasions, from the homes of 10 pregnant hypertensive women. On almost every occasion, the blood pressure measured at home was lower than that previously measured in the hospital antenatal clinic. This technique offers great promise, both in terms of health economics and also in terms of reducing pregnant women's unhappiness about their being admitted to hospital whenever they exhibit moderate to severe hypertension in the antenatal clinic. Indeed, in the antenatal period, home telemetry should allow the vast majority of hypertensive pregnancies to be managed just as safely at home as in hospital. In the management of high risk pregnancy, home telemetry of maternal blood pressure complements three other home telemetric techniques which have already been described: fetal heart rate, maternal blood glucose and uterine contractions.

Adult↗

CEUSPEC--a computerized system for fetal home telemetry.

We have developed a computerized system whereby the fetal heart rate can be recorded telemetrically from patients' homes, transmitted over conventional public telephone lines, and then computer-processed in real time in the obstetric unit.

Biometry↗

Cycloplegic refractions of premature infants.

Cyclopentolate refractions of 146 premature infants disclosed higher incidences of myopia and anisometropia than those reported for full-term infants. Also, more than 70% of the premature infants had I diopter or more of astigmatism; 83% of the astigmatism was against-the-rule. Infants with shorter gestational periods had more severe myopia and astigmatism. Infants born very prematurely should undergo follow-up refractions to determine whether they retain refractive errors large enough to interfere with visual function.

Age Factors↗

Improved viscometric assay for cellulase.

A viscometric assay for the determination of carboxymethylcellulase activity is described. The method, which is developed from a direct theoretical approach, takes into account a kinetic energy correction and the non-Newtonian behaviour of carboxymethylcellulose solutions. The enzymic hydrolysis of carboxymethylcellulose shows strong competitive inhibition by the products of the reaction and a method is presented for estimating the initial velocity of such reactions. A direct chemical determination of reducing end groups was used to confirm the validity of this approach.

Carboxymethylcellulose Sodium↗