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Biomedical subjects

J Grove

Publications and source records attributed to J Grove.

At least 19 recordsLinked to original sources

Mucoadhesion of copolymers and mixtures containing polyacrylic acid.

Water-soluble polymers were synthesized from dextran and polyacrylic acid and their ocular mucoadhesion was evaluated. One series had polyacrylic acid grafted onto the polysaccharide backbone of dextran, and another series had dextran grafted onto the polyacrylic acid backbone. Mucoadhesion of these copolymers was investigated using a tensile apparatus and compared with that of polyacrylic acid/dextran mixtures prepared in different proportions. Whatever the copolymer structure, no synergistic effects were seen and mucoadhesion was not markedly increased compared to dextran. The adhesion of copolymers was the same as that of mixtures having a similar polyacrylic acid content and was always less than that of polyacrylic acid alone. Formation of an interpolymer complex occurred at concentrations up to 60% polyacrylic acid, and only above this value did bioadhesion increase above that of dextran. When this complex was dissociated by neutralization of the carboxyl groups of polyacrylic acid, the mucoadhesion of the copolymers and the mixtures was improved. These experiments demonstrated that copolymers and mixtures of dextran and polyacrylic acid did not produce polymers with improved ocular mucoadhesion.

Acrylic Resins

Characteristics of children with specific language impairment attending language units.

The characteristics of children with specific language impairment (SLI) attending four language units in the north-west of England are examined. The present study involved 15 children with SLI and two sets of control groups: a same-age group and an MLU-matched group (MLU = mean length of utterance). Results are discussed in terms of the following questions: Do children with SLI attending language units fit the classic definition of SLI? Can children with SLI be categorised as having expressive versus receptive language problems? What other aspects of educational attainment such as reading, maths and science are affected by SLI? The paper ends with implications for future research.

Child

Rate of growth in length of Bangladeshi infants as a function of attained length.

We examine variation in the rate of growth in length of breast-feeding infants from rural Bangladesh. These data were collected between November 1985 and February 1986 from two rural sites. Eighty-eight infants, ranging from birth to 4 months of age at the start of the study and their mothers were measured monthly for 4 months. Length increased linearly with age over this 4-month period (infants' average bias-adjusted R2 = 0.90). The relationship between infant rate of growth in length and attained length was analyzed by two different methods: Oldham's (1962) method of regressing rate of growth on mean length and Blomqvist's (1977) method of regressing rate of growth on estimated initial length. The methods gave similar results. The rate of growth was negatively associated with mean infant length over the 4-month period (p less than 0.001); that is, shorter infants grew at a faster rate than longer infants. For every centimeter shorter the infant was, the rate of growth was 0.1 cm/mo faster on average; the effect was greater among males than among females. The average rate of growth was greater for males than for females and greater in financially solvent households and varied by site. Infant growth rate was slower among older infants than among younger infants, as expected. However, after adjusting for mean infant length, age was no longer significantly associated with infant growth rate, although mean infant length remained highly significant. Forty-one percent of the variation in infant rate of growth in length was explained by mean infant length, sex, sex by length interaction, household financial solvency, and site.

Age Factors

A method for assessing patterns of familial resemblance in complex human pedigrees, with an application to the nevus-count data in Utah kindreds.

An analytic method is described for estimating phenotypic correlations between pairs of members of specific relationships in pedigrees. In estimating correlations, this new method allows simultaneous adjustment for available covariates such as age, gender, environmental factors, and variables reflecting ascertainment mode, through mean- and variance-regression models. The estimated correlations and regression coefficients corresponding to covariates are consistent and asymptotically normally distributed. Differing from a full-likelihood approach, this new method does not require the assumption of a particular joint distribution of phenotypes from a pedigree, such as the multivariate normal distribution, but instead only requires correct specification of mean- and variance-regression models. Within this framework, missing data, if they are missing completely at random, can be ignored without biasing estimates. The method is illustrated by an application using nevus-count data from 28 Utah kinships. The results from the analysis are that covariate-adjusted nevus counts are correlated between parents and children (correlation .22; P less than .001) and between siblings (correlation .32; P less than .001), while the correlation of -.04 between husband and wife is not significantly different (P = .31) from 0. This result is consistent with a genetic etiology of nevus count.

Dysplastic Nevus Syndrome

Effects of acetylcysteine on rabbit conjunctival and corneal surfaces. A scanning electron microscopy study.

Conjunctival and corneal epithelial surfaces of normal rabbit eyes with their associated mucus were studied by scanning electron microscopy before and after treatment with the mucolytic agent N-acetylcysteine (AC). Four groups received topically one 50-microliters drop of either (Group A) 0.1 MAC, (Group B) 0.1 M AC every 5 min for 1 hr, (Group C) 0.1 M AC every 5 min for 2 hr, or (Group D) three drops of 20% AC over 15 min. The effects of the instillation of AC on mucus removal and cellular lesions increased in the order (A) less than (B) less than (C) less than (D). Treatment A had no effect on cornea and conjunctiva. Treatment B cleaned away mucosal debris without alteration of either conjunctival or corneal epithelium. Treatment C had a similar effect on the mucus but was associated with focal necrosis, and treatment D produced widespread necrosis, desquamation of epithelial cells, and inflammation.

Acetylcysteine

MK-927: a topically active ocular hypotensive carbonic anhydrase inhibitor.

MK-927 (dl-5,6-dihydro-4-(2-methylpropylamino)-4H-thieno(2,3b)thiopyra n-2-sulfonamide-7,7-dioxide hydrochloride) is a water soluble, carbonic anhydrase inhibitor (CAI) possessing a Ki of 12.0 nM against purified human carbonic anhydrase II in vitro. The acute instillation of one drop (50 microliters) of 0.5%, 1% and 2% solutions of MK-927 maximally decreased the intraocular pressure (IOP) of ocular hypertensive, cynomolgus monkeys by 4.7, 5.9 and 9.6 mm Hg, respectively. The decline of 9.6 mm Hg represented a reduction of 27% from the corresponding vehicle-treated value of 35.3 mm Hg. Peak reductions in IOP were present at 2 to 4 hr after the instillation of the three doses and the ocular hypotensive effect was waning at 6 hr. The IOP of normotensive, monkey eyes was significantly lowered by 1% and 2% solutions of MK-927 with the effect being more transient in these eyes than in hypertensive eyes. The elevated IOP of alpha-chymotrypsinized rabbits was dose-dependently decreased by 0.01%, 0.1% and 0.5% solutions of MK-927. MK-927 modestly bound to rabbit ocular pigment in vitro and the concentrations of MK-927 in the iris + ciliary body of pigmented rabbits were higher than those in the same tissue of albino rabbits after dosing with 0.5% MK-927. The ocular hypotensive effect of 2% MK-927 was greater in magnitude and longer in duration in normal pigmented than in albino rabbits. The IOP lowering action of MK-927 was local as evidenced by results of ocular distribution studies and the observation that the unilateral instillation of 0.5% MK-927 into the contralateral eye was devoid of effect on the untreated, hypertensive eye of alpha-chymotrypsinized rabbits. MK-927 has been selected for topical evaluation in glaucoma patients.

Administration, Topical

Scintigraphic assessment of an ophthalmic gelling vehicle in man and rabbit.

Studies of the rate of clearance of a gellan gum formulation (Gelrite) radiolabelled by the inclusion of technetium-99m labelled diethylenetriaminepentaacetic acid were carried out in volunteer subjects and in rabbits. Disposition was followed by gamma scintigraphy and compared with 0.5% w/v hydroxyethylcellulose (HEC) solution and isotonic saline administered to the same subjects. Clearance of all solutions was found to follow bi-exponential kinetics with differences in clearance rates between the two species studied. A significant retention of the gellan gum formulation compared to HEC (p = 0.006) or saline (p = 0.009) was noted in man, but not in the rabbit. In this latter species the HEC showed greater retention compared to Gelrite. The species-specific differences in the precorneal residence of the formulations are attributed to the different physiological responses following instillation of solutions into the eye.

Analysis of Variance

Studies on polyamine biosynthesis in Euglena gracilis.

Euglene gracilis (strain Z) was found to contain five polyamines which could be separated by high-pressure cation-exchange chromatography. 1,3-Diaminopropane, putrescine, norspermidine (N-(3-aminopropyl)-1,3-diaminopropane), spermidine and norspermine (N,N'-bis(aminopropyl)-1,3-diaminopropane) were identified. Biosynthesis of putrescine in E. gracilis proceeds through decarboxylation of L-ornithine, no arginine decarboxylase (EC 4.1.1.19) activity could be detected. The properties of the enzymes ornithine decarboxylase (EC 4.1.1.17) and S-adenosylmethionine decarboxylase (EC 4.1.1.50) in this alga were found to be similar to those of the enzymes isolated from animal tissues or yeast cells. A bioxynthetic scheme is proposed which relates the different polyamines occurring in E. gracilis.

Adenosylmethionine Decarboxylase

Effects of alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor or ornithine decarboxylase, on testosterone-induced regeneration of prostate and seminal vesicle in castrated rats.

1. Castration of adult rats markedly decreases the amounts of polyamines (putrescine, spermidine and spermine) and of RNA and DNA in the ventral prostate and the seminal vesicle. 2. Daily injections of testosterone propionate to rats castrated 7 days previously increase polyamine and nucleic acid contents more rapidly in the seminal vesicle than in the ventral prostate. 3. After 7 days of androgen treatment, polyamine and nucleic acid contents of the seminal vesicle are significantly higher than those of intact animals. Nucleic acid, but not polyamine, contents return to normal values during the next 4 days of continued treatment. In the prostate, androgen treatment increases polyamine and nucleic acid contents to, but not above, normal values. 4. Repeated doses of alpha-difluoromethylornithine, a potent enzyme-activated irreversible inhibitor of ornithine decarboxylase, totally blocked the testosterone-induced increase of putrescine and spermidine in the ventral prostate and of putrescine in the seminal vesicle. They slowed significantly the accumulation of spermine in the ventral prostate and of spermidine in the seminal vesicle. alpha-Difluoromethylornithine also retarded the testosterone-induced accumulation of RNA in the ventral prostate. However, no clear correlation was apparent between accumulation of polyamines and of nucleic acids in the two organs. 5. alpha-Difluoromethylornithine markedly slows the testosterone-induced weight gain of the prostate, but not of the seminal vesicle. Cytological studies suggest that this effect on the prostate is due to inhibition of the androgen-induced restoration of the secretion content of prostatic acini.

Animals

Rapid method for the assay of 4-aminobutyric acid (GABA), glutamic acid and aspartic acid in brain tissue and subcellular fractions.

The thin-layer electrophoretic separation at pH 4.8 of brain extracts and a procedure for fluorescent staining of the plates with fluorescamine are described for the rapid routine determination of 4-aminobutyric acid (GABA), glutamic acid and aspartic acid in brain extracts and in particulate fractions of brain tissue. Automated sample application, electrophoretic separation using two chambers, and quantitation by in situ fluorescence scanning allows the assay of 280 samples within three working days. The method is reproducible (S.D. less than 8% of the mean) within the range of 0.2--2 nmole per spot. The staining procedure can be applied to a variety of related analytical problems. The method has proved useful for the determination of the specific radioactivities of GABA, glutamic acid and aspartic acid in metabolic studies.

Aging

Regulatory interrelations between GABA and polyamines. I. Brain GABA levels and polyamine metabolism.

Elevation of brain GABA levels by GABA-T inhibition is accompanied by a decrease of S-adenosylmethionine decarboxylase activity. This is followed by an increase of ornithine decarboxylase activity and a severalfold increase of brain putrescine levels. Spermidine and spermine levels are not significantly affected under these conditions. These unexpected findings support a regulatory interaction between GABA and polyamine metabolism.

4-Aminobutyrate Transaminase