Biomedical subjects

T C Jenkins

Publications and source records attributed to T C Jenkins.

At least 127 records · Page 7Linked to original sources

PubMed1991

Binocular interaction with neutral density filters as measured by the visual evoked response.

The influence of neutral density (ND) filters on the pattern visually evoked response (VER) was investigated as a function of check size. Monocular and binocular transient pattern reversal VER's were recorded through three ND filters (0.6, 1.0, and 2.6 log units) before 1 eye on 55 adult subjects using 5.5 min arc and 50 min arc check sizes. The 5.5 min arc check produced responses which suggest that partial binocular summation is present in the absence of ND filters but disappears as the filter density increases. In the case of the 50 min arc check size the presence of binocular summation is less certain and a 1.0 log unit ND filter produces binocular inhibition which may be due to latency differences between the two eyes. Eye dominancy appears to have no effect on these results.

Adolescent↗

PubMed1991

Effect of ammonium carbamate on nutritive and preservative characteristics of high-moisture coastal bermudagrass hay.

Two studies evaluated the effects of ammonium carbamate (AC) on preservation and digestibility of high-moisture (HM) Coastal bermudagrass (Cynodon dactylon) hay. A 3 X 7 factorial arrangement of treatments in a completely random design was used to estimate the efficacy of AC in laboratory conditions. Treatments were 25, 30, or 35% moisture (M) forage treated with levels (L) of 0, 1.14, 2.28, 3.42, 4.56, 5.70, or 6.84% AC. Nitrogen in forage increased (P less than .01) linearly due to M and L. There was a linear decrease (P less than .01) in ADF N due to M. Neutral detergent fiber decreased (P less than .01) linearly as M increased and increased (P less than .01) linearly with increased L. Acid detergent fiber decreased (P less than .01) linearly due to L. There was an M X L interaction (P less than .01) for hemicellulose (HC) concentrations and total aerobic fungal counts. The digestibility of HM hay treated with a product (ACNH) containing 57% AC was compared to that of untreated hay (UH) and UH plus urea (UHU) when fed to lambs (four lambs per treatment). Digestibility of NDF and hemicellulose (P less than .01) and ADF (P less than .05) was increased for ACNH forage compared with UH or UHU. Ammonium carbamate seems to be beneficial for preserving HM forage, and an admixture containing ammonium carbamate is effective for increasing the digestibility of Coastal bermudagrass hay.

Analysis of Variance↗

PubMed1991

Distance and near readings of associated heterophoria taken on 500 patients.

Distance and near readings of associated heterophoria were taken, using standard Mallett units, on 500 patients passing consecutively through an optometric practice and any symptoms, connected with distance and near vision, were noted. Complete sets of results were obtained on 383 people. Distance readings, either in size or direction, did not appear related to symptoms and such readings did not appear helpful in patient management. For near vision a fair degree of association existed between readings of associated phoria and symptoms and it was possible in the under 40 years and 40-59 years age groups to express clinically useful rules regarding the relationship. Over 60 years of age such a relationship was complicated by the fact that high degrees of exophoria readings existed in both symptomatic and asymptomatic patients and it is suggested that this may be related to the quality of binocular vision.

Adolescent↗

PubMed1990

Interaction of berenil with the tyrT DNA sequence studied by footprinting and molecular modelling. Implications for the design of sequence-specific DNA recognition agents.

We have developed a technique of partially-restrained molecular mechanics enthalpy minimisation which enables the sequence-dependence of the DNA binding of a non-intercalating ligand to be studied for arbitrary sequences of considerable length (greater than = 60 base-pairs). The technique has been applied to analyse the binding of berenil to the minor groove of a 60 base-pair sequence derived from the tyrT promoter; the results are compared with those obtained by DNAse I and hydroxyl radical footprinting on the same sequence. The calculated and experimentally observed patterns of binding are in good agreement. Analysis of the modelling data highlights the importance of DNA flexibility in ligand binding. Further, the electrostatic component of the interaction tends to favour binding to AT-rich regions, whilst the van der Waals interaction energy term favours GC-rich ones. The results also suggest that an important contribution to the observed preference for binding in AT-rich regions arises from lower DNA perturbation energies and is not accompanied by reduced DNA structural perturbations in such sequences. It is therefore concluded that those modes of DNA distortion favourable to binding are probably more flexible in AT-rich regions. The structure of the modelled DNA sequence has also been analysed in terms of helical parameters. For the DNA energy-minimised in the absence of berenil, certain helical parameters show marked sequence-dependence. For example, purine-pyrimidine (R-Y) base pairs show a consistent positive buckle whereas this feature is consistently negative for Y-R pairs. Further, CG steps show lower than average values of slide while GC steps show lower than average values of rise. Similar analysis of the modelling data from the calculations including berenil highlights the importance of DNA flexibility in ligand binding. We observe that the binding of berenil induces characteristic responses in different helical parameters for the base-pairs around the binding site. For example, buckle and tilt tend to become more negative to the 5'-side of the binding site and more positive to the 3'-side, while the base steps at either side of the centre of the site show increased twist and decreased roll.

Amidines↗

PubMed1990

Crystal structure of a berenil-dodecanucleotide complex: the role of water in sequence-specific ligand binding.

The three-dimensional structure of a complex between the dodecanucleotide d(CGCGAATTCGCG) and the anti-trypanocidal drug berenil, has been determined to a resolution of 2.5 A. The structure has been solved by molecular replacement and refined to an R factor of 0.177. A total of 49 water molecules have been located. The drug is bound at the 5'-AAT-3' region of the oligonucleotide. At one end of the drug the amidinium group is in hydrogen-bonded contact with N3 of the adenine base complementary to the thymine of the AAT. The other amidinium group does not make direct interactions with the DNA. Instead, a water molecule mediates between them. This is in hydrogen-bonded contact with an amidinium nitrogen atom, N3 of the 5' end adenine base and the ring oxygen atom of an adjacent deoxyribose. Molecular mechanics calculations have been performed on this complex, with the drug at various positions along the sequence. These show that the observed position is only 0.8 kcal/mol higher in energy than the best position. It is suggested that there is a broad energy well in the AATT region for this drug, and that water molecules as well as the neighbouring sequence, will determine precise positioning. More general aspects of minor groove binding are discussed.

Amidines↗

PubMed1990

Synthesis and evaluation of alpha-[[(2-haloethyl)amino]methyl]-2- nitro-1H-imidazole-1-ethanols as prodrugs of alpha-[(1-aziridinyl)methyl]-2- nitro-1H-imidazole-1-ethanol (RSU-1069) and its analogues which are radiosensitizers and bioreductively activated cytotoxins.

alpha-[(1-Aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanols, of general formula ImCH2CH(OH)CH2NCR1R2CR3R4, where Im = 2-nitroimidazole and R1, R2, R3, R4 = H, Me, are radiosensitizers and selective bioreductively activated cytotoxins toward hypoxic tumor cells in vitro and in vivo. Treatment of the aziridines with hydrogen halide in acetone or aqueous acetone gave the corresponding 2-haloethylamines of general formula ImCH2CH(OH)CH2(+)-NH2CR1R2CR3R4X X-, where R1, R2, R3, R4 = H, Me, and X = F, Cl, Br, I. These 2-haloethylamines were evaluated as prodrugs of the parent aziridines. The rates of ring closure in aqueous solution at pH approximately 6 were found to increase with increasing methyl substitution and to depend on the nature of the leaving group (I approximately Br greater than Cl much greater than F). A competing reaction of ImCH2CH(OH)CH2+NH2CH2CH2X X- (X = Cl, Br) with aqueous HCO3- ions gives 3-[2-hyroxy-3-(2-nitro-1H-imidazol-1-yl)propyl]-2-oxazolidinone. The activities of these prodrugs as radiosensitizers or as bioreductively activated cytotoxins were consistent with the proportion converted to the parent aziridine during the course of the experiment. alpha-[[(2-Bromoethyl)amino]methyl]-2-nitro-1H-imidazole-1- ethanol (RB 6145, 10), the prodrug of alpha-[(1-aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanol (RSU-1069, 3), is identified as the most useful compound in terms of biological activity and rate of ring closure under physiological conditions.

Animals↗

PubMed1990

The electroretinogram in minimal diabetic retinopathy.

The pattern and diffuse flash electroretinograms were measured in 20 normal subjects and 40 diabetic patients who had either normal fundi or microaneurysms only. The amplitudes of the pattern electroretinogram were found to be similar in both normals and diabetics. In the case of the flash electroretinogram the diabetic patients showed a division into two main groups. One group was not dissimilar to the group of normal subjects, while the second group showed hypernormal amplitudes. No explanation could be given, from the data collected, for this subdivision, though it is suggested it might reflect the degree of metabolic disturbance.

Adult↗

PubMed1990

Effect of dietary energy restriction on metabolic and endocrine responses during the estrous cycle of the suckled beef cow.

A replicated trial was conducted with suckled Angus and Polled Hereford cows (110 d postcalving) to determine metabolic and endocrine responses to an energy-restricted diet after cows had re-established postpartum estrous cyclicity. Cows were individually fed 26.5 Mcal ME (H) or 15.2 Mcal ME (L) for a 30-d preliminary period and fitted with an indwelling jugular cannula at synchronized estrus. Average daily weight change during the estrous cycle was .60 +/- .25 and -1.37 +/- .30 kg/d for H and L, respectively (P less than .05). Blood concentrations of cortisol, progesterone and LH during the estrous cycle were not affected by diet, nor did diet affect frequency or amplitude of LH pulses (P greater than .05). No dietary differences were observed for daily concentrations of total protein, glucose, nonesterified fatty acids or acetate. Mean blood concentrations of propionate and butyrate were not different between diets; however, L cows had lower concentrations of propionate and butyrate on d 11 of the cycle (P less than .05). Cows fed L had higher concentrations of blood urea nitrogen (P less than .05), but they had lower concentrations of cholesterol (P less than .05) on d 4, 11, 18 and subsequent estrus (E). Insulin was not different on d 4 and 11; however, cows fed L had lower insulin concentrations on d 18 and d E (P less than .05). Dietary energy restriction in these cyclic cows caused no change in endocrine responses. Of metabolic responses measured, only blood urea nitrogen, cholesterol and insulin showed consistent changes.

Animals↗

PubMed1990

Effects of lecithin and corn oil on site of digestion, ruminal fermentation and microbial protein synthesis in sheep.

Six Hampshire wethers with ruminal and duodenal cannulas were fed three diets in a replicated 3 X 3 latin square to compare phospholipids with triglycerides for their effects on ruminal digestion. The diets (56% concentrate, 44% bermuda-grass hay, air-dried basis) contained either no added fat (control), 5.2% soybean lecithin or 2.4% corn oil on a DM basis. All diets were isonitrogenous and both fat-supplemented diets had similar fatty acid and energy contents. Fat added to the diet, regardless of source, reduced digestibilities of DM, energy, ADF and fatty acids in the rumen but had no effect on total tract digestibility coefficients. Lecithin slightly increased (P = .06) fatty acid digestion in the hindgut compared to corn oil (91.0 and 87.0%, respectively). Both fat sources decreased (P less than .01) ruminal ammonia concentration and increased (P less than .10) N flow to the duodenum. Added fat also reduced ruminal (P less than .01) and total tract (P less than .05) N digestibilities. Microbial N flow to the hindgut was not affected by diet, but adding fat increased (P less than .06) true efficiency of microbial protein synthesis. Overall, phospholipids from soybean lecithin inhibited ruminal fermentation similarly to triglycerides from corn oil. Despite ruminal degradation of lecithin by microbial phospholipases as shown in other studies, feeding lecithin tended to increase fatty acid digestion in the hindgut.

Animals↗

PubMed1990

Nutrient digestion, ruminal fermentation and plasma lipids in steers fed combinations of hydrogenated fat and lecithin.

Commercial soybean lecithin replaced hydrogenated fat in steer diets to determine if phospholipids enhance fatty acid digestion and microbial fermentation in ruminants. Four diets were fed in a 4 x 4 Latin square to four Angus steers with ruminal cannula. One diet contained no added fat (control) and three contained hydrogenated fat and lecithin in weight ratios of 100:0, 86:14, and 72:28. All diets with added fat had lower fatty acid digestibilities compared with the control diet with no difference due to level of lecithin. Ruminal acetate and acetate:propionate ratios were reduced by all fat supplements but reduced less for the supplements containing lecithin. Plasma triglyceride and cholesterol concentrations were increased from dietary fat but not increased as much if lecithin were present in the diet. Feeding lecithin to ruminants does not improve digestibility of hydrogenated fats that are highly saturated.

Animals↗

PubMed1990

Binocular summation in visually evoked responses and visual acuity.

Monocular and binocular transient visually evoked responses (VER) were recorded on 50 adult subjects using a pattern reversal stimulus (check size 5.5 min arc). The peak-to-trough amplitude of the VER wave was measured and compared with the subjective visual acuity (Landolt C). The binocular amplitude enhancement over the monocular amplitude was around 26% across the acuity range studied, whereas the mean binocular subjective visual acuity improvement was around 11.3%, but this varied from 1% at the high acuity end to 17% at the low acuity end of the range.

Adolescent↗

PubMed1990

Dual-function 2-nitroimidazoles as hypoxic cell radiosensitizers and bioreductive cytotoxins: in vivo evaluation in KHT murine sarcomas.

The efficacies of a series of potential prodrugs of RSU-1069 and its alkyl-aziridine analogues were assessed. These 1-(2-haloethylamino)-3-(2-nitro-1-imidazolyl)-2-propanol compounds were designed to cyclize in vivo to generate 2-nitro-imidazoles with aziridine (RSU-1069) or alkyl-substituted aziridine (RSU-1164, RB-7040, or RSU-1150) functions. Maximum tolerated single, intraperitoneal doses (MTD) were determined in C3H/He mice bearing subcutaneous KHT sarcomas, and a drug dose-response relationship for radiosensitization was established for each compound administered at the optimum time (45-60 min) before local irradiation of tumors with a 10-Gy dose of X-rays. The potentials of the compounds as bioreductive cytotoxins were studied by administering them immediately after irradiation. Tumor cell survival was measured 18-24 h after treatment in an in vitro soft agar clonogenic assay. Results of toxicity, radiosensitization, and bioreductive cytotoxicity assays for each of the prodrugs (RB-6171, RB-6172, RB-6173, RB-6174, and RB-6175) of the alkyl-substituted aziridines were entirely consistent with complete conversion to their respective target compounds. For example, RB-6171 (the prodrug form of RSU-1164) was only about four times less efficient than RSU-1069 as a radiosensitizer and bioreductive cytotoxin but had an MTD 7.5 times higher. In contrast, prodrugs of RSU-1069 (RB-6144 and RB-6145) were two- to threefold less toxic than their expected product. RB-6144 was a poor radiosensitizer and bioreductive agent compared with RSU-1069 and was similar to RB-6170, a nonalkylating nitroimidazole. This is consistent with the observation that there is limited conversion of RB-6144 to RSU-1069 in vitro. However, radiosensitization and bioreductive cytotoxicity produced by RB-6145 were only slightly less than the effects produced by RSU-1069; thus a therapeutic gain was achieved with RB-6145 in a murine tumor model.

Animals↗

PubMed1990

The non-covalent interaction of pyrrolo[2, 1-c] [1, 4]benzodiazepine-5, 11-diones with DNA.

A series of 15 pyrrolo[2, 1-c] [1, 4]benzodiazepine-5, 11-diones has been synthesized and evaluated for in vitro DNA binding by thermal denaturation and fluorescence quenching studies with calf thymus (CT) DNA. The results indicate that two compounds of the series, 7 and 8, elevate the melting point of DNA by 2.9 +/- 0.6 and 3.3 +/- 0.8 K, respectively. Similarly, a significant quenching of the fluorescence of the dihydroxy analogue 8 was observed upon interaction with CT-DNA. As controls, the dihydroxy isomer 9 with the reverse stereochemistry at C2 and the non-substituted parent dilactam 12, failed to increase the DNA melting point or exhibit significant quenching upon interaction with DNA. In addition, preliminary experiments with GC- and AT-rich polymers suggest some sequence-dependent properties for dilactams 7 and 8. Overall, these results indicate a highly specific structural requirement for DNA binding. Molecular modelling with d(GTAGATC), d(GCAGATC) and d(GCGTAGC) duplex sequences has provided a model based on hydrogen bonding between the dihydroxy dilactam 8 and DNA, that rationalizes some of the results obtained. It is possible that the observed interactions represent the non-covalent (binding) component of the interaction of covalently-bonding anthramycin-type anti-tumour antibiotics with DNA.

Anthramycin↗

PubMed1989

Binocular vision without visual stress.

The use of changes in fixation disparity, the associated phoria, and the dissociated phoria in assessing the degree of visual stress requires that we know the effect of vision under close working conditions (40 cm) on these parameters. The authors have previously reported that reading under the stress of abnormally low illumination, or at too close a working distance (20 cm), increases fixation disparity and associated phoria and is associated with symptoms and visual discomfort. The current study shows that reading at photopic levels of illumination and at a working distance of 40 cm does not change the magnitudes of fixation disparity and associated phoria. Reading under these conditions is not accompanied by an onset of symptoms or visual discomfort. This result indicates that changes in fixation disparity and associated phoria are a product of visual stress and are not produced by reading itself.

Adolescent↗

PubMed1989

Binocular vision, age and symptoms.

Changes with age in heterophoria, associated heterophoria, fixation disparity and stereopsis for near vision were investigated in a sample of 187 subjects (age range from 10 to 65 years) divided into six age groups. With increasing age, heterophoria, associated heterophoria and fixation disparity increased in the exo-direction. No change in stereopsis was found. A comparison with visual symptoms for near vision indicated a relationship between symptoms and the magnitude of fixation disparity and associated heterophoria for all age groups, but no relationship was found between the presence of symptoms and heterophoria measurement. No relationship between the presence of symptoms and the central slope of the forced vergence fixation disparity curve was found. These findings suggested that neither the measurement of heterophoria nor the forced vergence disparity curve are appropriate tests in the assessment of binocular vision anomalies. However, fixation disparity and associated heterophoria are related to binocular problems for near vision in all age groups.

Adolescent↗

PubMed1989

Criteria for decompensation in binocular vision.

Two groups of patients, one under 40 years of age and the other 40 years and over, were divided into subgroups according to whether they had symptoms associated with near vision. A method developed in 'signal detection theory' was used to determine whether a value could be found for heterophoria, or associated heterophoria, which would predict which patients had symptoms due to decompensated heterophoria in normal routine investigation. Receiver operator characteristic curves (ROC curves) were constructed to look for these cut-off values between patients with, and without, symptoms. No value for dissociated heterophoria was found that would discriminate between the symptomatic and asymptomatic patients. It is concluded that heterophoria measurement is not useful as a routine procedure. In the case of associated heterophoria, for the under 40 years age group, patients with a value of 1 prism dioptre or more are more likely to have symptoms than not, and one-third of patients with close work problems have a value of 2 prism dioptres or more. It was rare to find any asymptomatic patient with a value as high as this. In the 40 years and over age group those with an associated heterophoria of 2 prism dioptres or more are more likely to have symptoms than not. One-third of patients in the latter age group, with symptoms, have a value of 3 prism dioptres or more whilst it is rare to find an asymptomatic patient with a value as large as this.

Adult↗

PubMed1989

Influence of phospholipids on ruminal fermentation in vitro and on nutrient digestion and serum lipids in sheep.

Phospholipid supplements were incubated in vitro or fed to sheep to determine how they affected ruminal fermentation, nutrient digestion and serum lipid concentration. In vitro, deoiled soybean lecithin added to hay increased (P less than .05) total VFA concentration but had no effect on fiber digestion in four of five trials. Purified phospholipid (synthetic phosphatidylethanolamine), however, had little effect on in vitro hay fermentation when tested at four levels (0, 10, 20 or 30 mg) in three separate trials. Deoiled soybean lecithin disappeared in vitro at two rates, 12.9 and .66%/h for the fast- and slow-degrading fractions, respectively. Compared with 2.4% corn oil supplements, 5.2% soybean lecithin added to sheep diets (56% concentrate) reduced (P less than .05) energy, fiber and nitrogen digestibilities. Crude lecithin reduced (P less than .05) energy digestibility more than deoiled lecithin. Both types of lecithin increased (P less than .05) serum nonesterified fatty acid concentrations but had no effect on serum glucose, cholesterol or triglyceride concentrations compared with the corn oil diet. In summary, phospholipids had different effects on ruminal fermentation, depending on their source. None had a beneficial effect on fiber digestion. Phospholipids are degraded in the rumen and inhibit digestion in a manner similar to that of the commercial fats and oils.

Animals↗

PubMed1989

Effect of hydrogenated fat on feed intake, nutrient digestion, and lactation performance of dairy cows.

Eight lactating Holstein cows were fed four diets in a replicated 4 x 4 Latin square design to determine how hydrogenation affects fats as supplements for dairy rations. Four isonitrogenous diets contained either no added fat, 5% yellow grease, or 3 or 5% hydrogenated yellow grease. Only yellow grease reduced DM intake compared with DM intake of the control diet. Diets supplemented with fat had lower digestibilities of fiber, nitrogen, energy, and fatty acids than the control diet did. Ruminal acetate concentration and acetate to propionate ratio were higher for the hydrogenated fat than for yellow grease. However, fatty acid digestibilities were lower for diets containing hydrogenated fat. Milk yields of fat-supplemented diets, whether actual or 4% FCM, did not exceed the control diet except for 5% hydrogenated yellow grease. This study shows that hydrogenated fats have fewer negative effects on food intake, milk fat content, and ruminal fermentation but have lower digestibilities than other fats. Hydrogenation improved milk yield compared with yellow grease fed at the same amount of supplementation.

Animal Feed↗