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Biomedical subjects

I Hutchinson

Publications and source records attributed to I Hutchinson.

At least 19 recordsLinked to original sources
PubMed2001

Antitumor benzothiazoles. 14. Synthesis and in vitro biological properties of fluorinated 2-(4-aminophenyl)benzothiazoles.

Synthetic routes to a series of mono- and difluorinated 2-(4-amino-3-substituted-phenyl)benzothiazoles have been devised. Whereas mixtures of regioisomeric 5- and 7-fluoro-benzothiazoles were formed from the established Jacobsen cyclization of precursor 3-fluoro-thiobenzanilides, two modifications to this general process have allowed the synthesis of pure samples of these target compounds. Fluorinated 2-(4-aminophenyl)benzothiazoles were potently cytotoxic (GI(50) < 1 nM) in vitro in sensitive human breast MCF-7 (ER+) and MDA 468 (ER-) cell lines but inactive (GI(50) > 10 microM) against PC 3 prostate, nonmalignant HBL 100 breast, and HCT 116 colon cells. The biphasic dose-response relationship characteristically shown by the benzothiazole series against sensitive cell lines was exhibited by the 4- and 6-fluoro-benzothiazoles (10b,d) but not by the 5- and 7-fluoro-benzothiazoles (10h,i). The most potent broad spectrum agent in the NCI cell panel was 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (10h) which, unlike the 6-fluoro isomer (10d), produces no exportable metabolites in the presence of sensitive MCF-7 cells. Induction of cytochrome P450 CYP1A1, a crucial event in determining the antitumor specificity of this series of benzothiazoles, was not compromised. 10h is currently the focus of pharmaceutical and preclinical development.

Antineoplastic Agents↗
PubMed2001

Analysis of taste mixtures by adults and children.

Children at mid-childhood (8-9 years), have limited perceptual-attentional skills to analyze complex stimuli (Shepp, Barrett, & Kolbet, 1987), and little is known of their skills to analyze chemosensory stimuli. Accordingly, this study investigated the ability of adults and 8-9 year old children to perceive tastes in binary mixtures. In Experiment 1, subjects used a selective attention procedure to indicate whether sweet, salty, and sour tastes were present in stimuli consisting of sucrose (sweet), sodium chloride (salty), citric acid (sour), and all possible binary mixtures of these tastants. Adults correctly recognized the two tastes in all mixtures, whilst children recognized only one in each mixture. Children were successful in recognizing sweet in both sweet-containing mixtures and salty in the sodium chloride-citric acid mixture. In Experiment 2, subjects used a similar selective attention paradigm to assess the perceived intensity of the three tastes in the above single and two-component stimuli. Suppression of one or both components was recorded with most mixtures by both age groups. However, with the mixture sodium chloride-citric acid, only the children recorded suppression of sourness, whilst for adults only saltiness was suppressed. In neither mixture containing sourness did children report suppression of sweetness or saltiness. It is concluded that at mid-childhood humans have difficulty analyzing taste mixtures into their components, due to attentional and possibly gustatory shortcomings.

Adolescent↗
PubMed2001

Identification of the components of taste mixtures by adults and children.

Recently, it was reported that cognitive factors may have impeded the analysis of binary taste mixtures by 8- to 9-year-old children, resulting in them identifying only the strongest component in each mixture compared to adults who identified both components (Oram, Laing, Freeman, & Hutchinson, 2001). The current study aimed to overcome this limitation by employing different training procedures and different instructions when conducting the task. In particular, the training involved familiarization with the two stimuli at several levels of perceived intensity to facilitate identification of the varying levels of each stimulus in mixtures. Using a selective attention procedure, adults and children were required to identify the components of stimuli that contained water, sucrose (sweet), sodium chloride (salty), or were binary mixtures of these two tastants. Both groups were successful in identifying the component(s) in each stimulus, demonstrating the importance of appropriate training and test procedures when studying the sensory responses of children. Together with data from the earlier study by Oram et al. (2001) it is concluded that 8- to 9-year-olds have the cognitive skills to analyze taste mixtures in terms of the identity of the components and their perceived strengths.

Adolescent↗
PubMed2001

A psychophysical study of the relationship between temporal processing in odor mixtures and transduction pathways.

Depending on the odorant, transduction during the olfactory reception process is reported to be mediated by the second messengers cyclic adenosine 3',5'-monophosphate (cAMP) or inositol 1,4,5-triphosphate (IP(3)). The present study with humans investigates the relationship between temporal processing in mixtures and the type of transduction process used. The most common outcomes were reciprocal temporal interactions which were primarily dependent on odorant concentration and independent of the type of transduction process. The results are consistent with the bulk of evidence that each receptor neuron commonly has only one type of receptor.

Adult↗
PubMed2001

Functional occlusion: II. The role of articulators in orthodontics.

Opinion is divided on whether there is a place for the use of semi-adjustable dental articulators in orthodontics. In this review we explore the validity and reproducibility of the techniques involved in mounting study models on a semi-adjustable dental articulator. We also look at the role of articulated study models in orthodontic diagnosis and treatment planning, in the finishing stages of orthodontics and in planning for orthognathic surgery. We report that each of the many stages involved in mounting study models on a semi-adjustable articulator is a potential source of error and that only if the technique is carried out with a high degree of accuracy is it worth the additional chairside time.

Dental Articulators↗
PubMed2000

Evidence for a genetic predisposition towards acute rejection after kidney and simultaneous kidney-pancreas transplantation.

BACKGROUND: In vitro production of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin 10 (IL-10), and transforming growth factor-beta (TGF-beta) correlate with their respective genetic polymorphisms. We analyzed the relationship between these genetic polymorphisms and posttransplant outcome. METHODS: Using DNA polymerase chain reaction (PCR) technology, polymorphisms for TNF-alpha, IFN-gamma, IL-10, and TGF-beta were determined for 82 kidney (K) and 19 simultaneous kidney-pancreas (SKP) recipients. These results were analyzed with regard to the incidence of acute rejection (AR), and the timing and severity of the first AR episode. RESULTS: A high TNF-alpha production phenotype correlated with recurrent acute rejection (AR) episodes (P<0.026). Compared with the low TNF-alpha production phenotype, more patients with the high production phenotype had a post-AR serum creatinine >2.0 mg/dl, but this was not statistically significant (64 vs. 35%, P=0.12). There was no relationship between TNF-alpha genotype and the time to first AR episode or incidence of graft loss. IFN-gamma production phenotype showed no correlation with any of these clinical outcome parameters. There was an increase in AR incidence as the IL-10 production phenotype increased (low, intermediate, high), but only in low TNF-alpha producer phenotypes (P=0.023). CONCLUSIONS: Patients with a polymorphic cytokine genotype putatively encoding for high in vivo TNF-alpha production, and to a lesser extent IL-10 cytokine genotypes putatively encoding for higher levels of in vivo IL-10 production, had a worse clinical outcome regarding AR episodes. These data support the hypothesis that the strength of alloimmune responsiveness after transplantation in part is genetically determined.

Acute Disease↗
PubMed1999

Antitumor benzothiazoles. 8. Synthesis, metabolic formation, and biological properties of the C- and N-oxidation products of antitumor 2-(4-aminophenyl)benzothiazoles.

2-(4-Aminophenyl)benzothiazoles 1 and their N-acetylated forms have been converted to C- and N-hydroxylated derivatives to investigate the role of metabolic oxidation in the mode of action of this series of compounds. 2-(4-Amino-3-methylphenyl)benzothiazole (1a, DF 203, NSC 674495) is a novel and potent antitumor agent with selective growth inhibitory properties against human cancer cell lines. Very low IC(50) values (<0.1 microM) were encountered in the most sensitive breast cancer cell lines, MCF-7 and T-47D, whereas renal cell line TK-10 was weakly inhibited by 1a. Cell lines from the same tissue origin, MDA-MB-435 (breast), CAKI-1 (renal), and A498 (renal), were insensitive to 1a. Accumulation and metabolism of 1a were observed in sensitive cell lines only, with the highest rate of metabolism occurring in the most sensitive MCF-7 and T-47D cells. Thus, differential uptake and metabolism of 1a by cancer cell lines may underlie its selective profile of anticancer activity. A major metabolite in these sensitive cell lines has been identified as 2-(4-amino-3-methylphenyl)-6-hydroxybenzothiazole (6c). Hydroxylation of 1a was not detected in the homogenate of previously untreated MCF-7, T-47D, and TK-10 cells but was readily observed in homogenates of sensitive cells that were pretreated with 1a. Accumulation and covalent binding of [(14)C]1a derived radioactivity was observed in the sensitive MCF-7 cell line but not in the insensitive MDA-MB-435 cell line. The mechanism of growth inhibition by 1a, which is unknown, may be dependent on the differential metabolism of the drug to an activated form by sensitive cell lines only and its covalent binding to an intracellular protein. However, the 6-hydroxy derivative 6c is not the 'active' metabolite since, like all other C- and N-hydroxylated benzothiazoles examined in this study, it is devoid of antitumor properties in vitro.

Aniline Compounds↗
PubMed1999

Antitumor benzothiazoles. 7. Synthesis of 2-(4-acylaminophenyl)benzothiazoles and investigations into the role of acetylation in the antitumor activities of the parent amines.

2-(4-Aminophenyl)benzothiazoles display potent and selective antitumor activity against inter alia breast, ovarian, colon, and renal cell lines, but their mechanism of action, though yet to be defined, may be novel. Metabolism is suspected to play a central role in the mode of action of these benzothiazoles since drug uptake and biotransformation were observed in sensitive cell lines (e.g., breast MCF-7 and MDA 468 cells) in vitro, whereas insensitive cell lines (e.g., prostate PC 3 cells) showed negligible uptake and biotransformation. N-Acyl derivatives of the arylamines have been synthesized, and in vitro studies confirm N-acetylation and oxidation as the main metabolic transformations of 2-(4-aminophenyl)benzothiazoles, with the predominant process being dictated by the nature of the 3'-substituent. The prototype amine 3 underwent mainly N-acetylation in vitro, while 3'-substituted analogues 4 and 5 were primarily oxidized. N-Acetylation of 4 to 11 exerts a drastic dyschemotherapeutic effect in vitro, but acetylation of the halogeno congeners 5-7 gave acetylamines 12-14 which substantially retain selective antitumor activity. In vivo pharmacokinetic studies in rats confirmed rapid and exclusive N-acetylation of the 3'-methyl analogue 4, but less acetylation with the 3'-chloro analogue 5. Distinct expression patterns of N-acetyltransferase NAT1 and NAT2 have been demonstrated in our panel of cell lines.

Acetylation↗
PubMed1999

Polymorphic haplotypes of the interleukin-10 5' flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis.

OBJECTIVE: To determine the distribution of the interleukin-10 (IL-10) 5' flanking region haplotypes in children with arthritis and in controls, and to investigate the functional significance of each haplotype. METHODS: Sequence-specific oligonucleotide probing was used to determine haplotype frequency. Transient transfection studies were used to investigate the transcription of reporter genes driven by each haplotype. Whole blood cultures were performed to assess IL-10 production by each genotype. RESULTS: Patients with arthritis involving >4 joints were more likely to have a genotype with an ATA haplotype than those whose arthritis remained restricted to <4 joints. This ATA haplotype was associated with lower transcriptional activity than the GCC haplotype (P = 0.02), and the ATA/ATA genotype was associated with lower IL-10 production under lipopolysaccharide stimulation than other genotypes (P < 0.02). CONCLUSION: The results of this study demonstrate the functional significance of the ATA haplotype and reveal a significant association of genotypes containing this haplotype with extended oligoarthritis.

Arthritis, Juvenile↗
PubMed1999

The development of meat-eating habits during childhood in Australia.

The development of meat-eating habits of 999 Australian children between 1 and 16 years of age stratified across socioeconomic groups, was determined using a 4-day diary and measurement procedures to document intake. The results indicated that a stable pattern of meat-eating behaviour, as regards the frequency and type of meat eaten was established during the period 1-4 years of age and remained until 10-12 years for males and until at least 14-16 years for females. In contrast, the amount of meat consumed increased with age, the greatest increases occurring with adolescent males who ate the largest amounts of beef, chicken and pork. It is suggested that the early establishment of meat-eating habits may reflect a more general effect that may occur with other types of food.

Adolescent↗
PubMed1999

Perception of sweetness in simple and complex taste stimuli by adults and children.

Currently, there is little information on the ability of children to analyse complex chemosensory stimuli in terms of the presence and magnitude of the components. The present study investigates this question by comparing the ability of 95 adults and 8- to 9-year-olds to estimate the sweetness of several concentrations of sucrose in water and in three foods, namely, orange drink, custard and shortbread biscuits, using a magnitude estimation procedure. The results indicated that similar response functions were produced by adults and children for the sweetness of aqueous solutions of sucrose, custard and biscuits, but not for orange juice, where the functions produced by both female and male children were significantly flatter than those of the adults. Stimulus context may have influenced the ratings of children in the no-sucrose and highest sucrose concentration conditions with two of the foods. The absence of differences between the response functions of the female and male children with all types of stimuli indicated that gender had no influence on their responses. It is concluded that, at mid-childhood, humans are capable of estimating the sweetness of sucrose in foods, but that they have a tendency to limit the range of numbers used in their estimates of sweetness at high concentrations of sucrose in some foods.

Adult↗
PubMed1999

Digital cameras.

Explore the source record for details and available documents.

Data Display↗
PubMed1999

Digital cameras and orthodontics: an overview.

The need to record clinical images, for use in documenting treatments, patient education, patient contracting, referral letters and sharing information with colleagues, is increasing. This article reviews the advantages and disadvantages of 35 mm and digital photography.

Dental Records↗
PubMed1998

Temporal processing of odor mixtures reveals that identification of components takes precedence over temporal information in olfactory memory.

Temporal processing of binary mixtures results in odorants being perceived in series separated by many hundreds of milliseconds. Since the odorant perceived first is the main suppressor, knowledge of the order of perception of two odorants can allow prediction of interactions in mixtures. The present study investigated the temporal coding of ternary mixtures composed of carvone, coniferan and triethylamine, and citralva, lillial and triethylamine using a specially constructed air-dilution olfactometer. The results indicated that even though each of the components could be readily identified in ternary mixtures, it was very difficult to indicate which odor was perceived first, with chance scores being recorded. The same outcome occurred even when the 'slowest' odorant was delivered 600 ms after the 'fastest' to the nose. It is proposed that olfactory memory gives precedence to identification of the components of mixtures rather than to their order of perception when more than two odorants are in a mixture.

Humans↗
PubMed1997

Fluorescent staining of kappa opioid receptors using naltrexamine derivatives and phycoerythrin.

An immunofluorescent technique that is more sensitive than radioligand binding was developed in order to detect opioid receptors expressed on leukocytes. The current study was designed to optimize the method for fluorescently labeling kappa opioid receptors. For these experiments, the opioid antagonist naltrexamine was conjugated to either fluorescein (FITC-NTXamine) or biotin (biotin-NTXamine). One-step, two-step, and three-step protocols were compared to determine which procedure resulted in optimal staining of the kappa opioid receptor expressed on intact, unfixed R1E/TL8x.1.OUAr.1(R1EGO) cells, a thymoma known to express kappa opioid receptors. The one-step method involved incubating cells with FITC-NTXamine, and the fluorescein intensity was measured by flow cytometry. In the two-step method, cells were incubated with biotin-NTXamine, followed by extravidin-conjugated phycoerythrin, and the phycoerythrin fluorescence was measured. Finally, in the three-step protocol, cells were incubated with FITC-NTXamine, followed by biotin-conjugated anti-fluorescein IgG, then extravidin-phycoerythrin. The one-step protocol stained the cells, but the signal was not diminished in the presence of opioid competitors. The two-step approach did not stain cells significantly above background levels. Only the three-step approach yielded staining that was displaced by the kappa-selective antagonist nor-binaltorphimine. Thus, the addition of a secondary biotinylated antibody, resulting in the amplification of binding, which was detected using phycoerythrin as a fluorophore, was required to detect low levels of opioid receptor expression on leukocytes.

Animals↗
PubMed1996

Juvenile systemic hyalinosis--a rare cause of gingival hypertrophy: a case report.

A 5-year-old boy was referred because of gross gingival hypertrophy which caused severe feeding difficulties in addition to obvious aesthetic concern. The patient also suffered from frequent upper respiratory tract infections and diarrhoea. In addition, he had pigmentation on bony prominences of his hands, elbows, knees and ankles, cutaneous nodules behind his ear and granulomatous tissue adjacent to his nose. Excess gingival tissue was removed under general anaesthesia. Histological features suggested a diagnosis of juvenile hyaline fibromatosis, which is considered to represent the same underlying pathological condition as infantile systemic hyalinosis. It is suggested that systemic hyalinosis should be preceded by 'infantile' or 'juvenile' depending on the clinical presentation.

Child, Preschool↗
PubMed1996

Mandibular enlargement: an unusual complication of a cervical cystic hygroma.

A 13-year-old boy with a large cervical cystic hygroma, which extended into the floor of mouth, was referred for treatment of painful teeth and tongue. Clinically there was a large submandibular swelling, enlargement of the mandible and a Class III malocclusion. Intra-orally the tongue was enlarged and vesiculated. Gross caries was present in both mandibular permanent first molar teeth. Treatment comprised oral hygiene instruction, dietary advice, chlorohexidene mouth rinse, and removal of the carious teeth. At a later data, removal of the lesion and correction of the mandibular enlargement will be undertaken.

Adolescent↗