Biomedical subjects

D S Hill

Publications and source records attributed to D S Hill.

At least 19 recordsLinked to original sources

PubMed2003

Use of laser microdissection greatly improves the recovery of DNA from sperm on microscope slides.

Traditionally, sperms are isolated from vaginal cell mixtures by preferential extraction methods. Although these methods work well when there is a reasonable amount of DNA present, they are problematic when there are limited amounts (ca. 250 pg). In particular, the analysis of sperm from microscope slides has proven difficult. Here, we describe the use of laser capture microdissection (LM) for the isolation of spermatozoa from microscope slides containing sperms and vaginal cells. Such slides are frequently an important source of evidential material during the forensic investigation of rape and other sexual assaults. Low copy number (LCN) PCR was used to compare profiles of sperm DNA prepared using LM and preferential lysis. LM was found to outperform preferential lysis in 15 out of 16 samples. The application of LM to the processing of actual casework slides, and in particular the potential use of LM for the analysis of old cases, is discussed. Finally, 77 post-coital slides were processed in order to accurately assess the robustness of the technique. There was a significant association between the quality of the male profile recovered and time since intercourse that was independent of the number of sperms analysed, suggesting that the DNA was degraded even though the spermhead was intact.

Alleles↗

PubMed2001

Shared processes in spatial rotation and musical permutation.

An experiment was conducted in which subjects performed a three-dimensional spatial rotation test (24 trials) and a new test involving judgments of musical permutations (64 trials). Two types of musical permutations were used, including retrograde and inverse. In a retrograde permutation, the criterion melody was played backward in the test melody, and in an inverse permutation, an ascending or descending interval in the criterion melody became an opposite in the test melody. Subjects included 32 male and 64 female undergraduates at the University of Toronto. Regression analysis clearly showed that it was easiest to compare short retrograde permutations and that accuracy at discerning retrograde permutations predicted accuracy at judging spatial rotations. The implication is that a higher order ability to discriminate contour underlies both kinds of judgments.

Female↗

PubMed2000

Quality of life issues in recurrent respiratory papillomatosis.

Twenty-six adult patients attending the Royal National Throat, Nose, and Ear Hospital with Recurrent Respiratory Papillomatosis completed two postal questionnaires. One was the generic Short Form-36 (SF-36) quality of life instrument. Severely affected patients had lower scores in all dimensions of this instrument, with large differences from normal controls in dimensions of pain, physical limitation, and energy/vitality. The second questionnaire was newly devised, and designed to ask about a wide variety of larynx-specific symptoms. Answers by patients were compared with those of normal controls, and symptoms selected as significantly more likely to be reported by patients were studied further. Correlation was seen with clinical parameters, and questions likely to be responsive to clinical change in disease burden were identified.

Adolescent↗

PubMed2000

A unique parotid adenocarcinoma.

A large number of different types of benign and malignant tumours of the salivary glands are recognized, and rare and unusual variants arise from time to time that can be difficult to interpret. We report an apparently unique parotid neoplasm that does not fit any of the currently recognized diagnostic groups and can best be termed lymphadenocarcinoma. Clinical and pathological features are described, and its possible relationship to recognized tumour types is examined.

Adenocarcinoma↗

PubMed1999

Conservation of the pyrrolnitrin biosynthetic gene cluster among six pyrrolnitrin-producing strains.

The prnABCD gene cluster from Pseudomonas fluorescens encodes the biosynthetic pathway for pyrrolnitrin, a secondary metabolite derived from tryptophan which has strong anti-fungal activity. We used the prn genes from P. fluorescens strain BL915 as a probe to clone and sequence homologous genes from three other Pseudomonas strains, Burkholderia cepacia and Myxococcus fulvus. With the exception of the prnA gene from M. fulvus59% similar among the strains, indicating that the biochemical pathway for pyrrolnitrin biosynthesis is highly conserved. The prnA gene from M. fulvus is about 45% similar to prnA from the other strains and contains regions which are highly conserved among all six strains.

Antifungal Agents↗

PubMed1998

A simple reconstructive procedure for radiation-induced necrosis of the external auditory canal.

Localized necrosis of the bone, cartilage, and soft tissue of the external auditory canal is an uncommon side effect of radiotherapy to the parotid region. Five patients developed late onset skin necrosis of a quadrant of the ear canal secondary to an underlying osteoradionecrosis of the tympanic ring. We report a one-stage procedure to excise the necrotic tissue and replace it with a local rotational flap derived from the post-auricular skin. Otological side effects of radiotherapy are discussed.

Adult↗

PubMed1998

Functions encoded by pyrrolnitrin biosynthetic genes from Pseudomonas fluorescens.

Pyrrolnitrin is a secondary metabolite derived from tryptophan and has strong antifungal activity. Recently we described four genes, prnABCD, from Pseudomonas fluorescens that encode the biosynthesis of pyrrolnitrin. In the work presented here, we describe the function of each prn gene product. The four genes encode proteins identical in size and serology to proteins present in wild-type Pseudomonas fluorescens, but absent from a mutant from which the entire prn gene region had been deleted. The prnA gene product catalyzes the chlorination of L-tryptophan to form 7-chloro-L-tryptophan. The prnB gene product catalyzes a ring rearrangement and decarboxylation to convert 7-chloro-L-tryptophan to monodechloroaminopyrrolnitrin. The prnC gene product chlorinates monodechloroaminopyrrolnitrin at the 3 position to form aminopyrrolnitrin. The prnD gene product catalyzes the oxidation of the amino group of aminopyrrolnitrin to a nitro group to form pyrrolnitrin. The organization of the prn genes in the operon is identical to the order of the reactions in the biosynthetic pathway.

Blotting, Western↗

PubMed1997

Stability of Legionella urinary antigens over time.

Twenty-two urine samples positive for Legionella pneumophila serogroup 1 antigen by EQUATE radioimmunoassay (RIA) (Binax, Portland, ME, USA) were stored at various temperatures and the RIA repeated at 1, 7, 30, 90, and 120 days to evaluate stability of the urinary antigens. The mean ratios of patient/negative control remained stable. Although there was a 10% decrease in the mean ratios after 1 month, changes were not significant. However, individual samples with ratios close to 3 may fall to < 3.

Antigens, Bacterial↗

PubMed1997

Mothers' and fathers' singing to infants.

Mothers and fathers sang a song of their choice, once to their infant and once as if to their infant (simulated). The pitch of songs was higher and the tempo slower for infant-directed than for simulated versions. Listeners varying in child-care experience, musical background, and cultural origin reliably identified which of the two versions was infant-directed (Experiment 1). Identification accuracy was enhanced by musical training, knowledge of the singers' language and culture, and by greater pitch and tempo differences between versions. Other adult listeners who rated the singer's emotional engagement assigned significantly higher ratings to infant-directed than to simulated versions (Experiment 2). Differences in pitch and tempo between both versions predicted emotional engagement ratings. Finally, rating differences between infant-directed and simulated versions were highly correlated with identification accuracy.

Adolescent↗

PubMed1997

Parents' sung performances for infants.

Naive listeners rated the style of singing in mothers' and fathers' sung performances for infants and their simulations of those performances (Experiment 1). Performances in an infant's presence were judged as more expressive--either more playful or more soothing--than were simulations. Parents' style of singing, as reflected in these ratings, differed as a function of the sex of singer and listener. Both parents sang more playfully for same-sex infants than for opposite-sex infants. Independent listeners rated the manner in which parents enunciated the lyrics of their songs (Experiment 2). Parents rendered the lyrics of songs more expressively in infant-present than in infant-absent contexts. Moreover, this expressiveness was greater for same-sex infants than for opposite-sex infants. These findings are consistent with parents' greater attachment to same-sex infants. Discrepancies between parents' choice of songs and their manner of singing lend credence to functional rather than nominal classifications of songs for infants.

Adult↗

PubMed1997

Four genes from Pseudomonas fluorescens that encode the biosynthesis of pyrrolnitrin.

Pyrrolnitrin is a secondary metabolite of Pseudomonas and Burkholderia sp. strains with strong antifungal activity. Production of pyrrolnitrin has been correlated with the ability of some bacteria to control plant diseases caused by fungal pathogens, including the damping-off pathogen Rhizoctonia solani. Pseudomonas fluorescens BL915 has been reported to produce pyrrolnitrin and to be an effective biocontrol agent for this pathogen. We have isolated a 32-kb genomic DNA fragment from this strain that contains genes involved in the biosynthesis of pyrrolnitrin. Marker-exchange mutagenesis of this DNA with Tn5 revealed the presence of a 6.2-kb region that contains genes required for the synthesis of pyrrolnitrin. The nucleotide sequence of the 6.2-kb region was determined and found to contain a cluster of four genes that are required for the production of pyrrolnitrin. Deletion mutations in any of the four genes resulted in a pyrrolnitrin-nonproducing phenotype. The putative coding sequences of the four individual genes were cloned by PCR and fused to the tac promoter from Escherichia coli. In each case, the appropriate tac promoter-pyrrolnitrin gene fusion was shown to complement the pyrrolnitrin-negative phenotype of the corresponding deletion mutant. Transfer of the four gene cluster to E. coli resulted in the production of pyrrolnitrin by this organism, thereby demonstrating that the four genes are sufficient for the production of this metabolite and represent all of the genes required to encode the pathway for pyrrolnitrin biosynthesis.

Amino Acid Sequence↗

PubMed1995

Four new derivatives of the broad-host-range cloning vector pBBR1MCS, carrying different antibiotic-resistance cassettes.

Four new antibiotic-resistant derivatives of the broad-host-range (bhr) cloning vector pBBR1MCS have been constructed. These new plasmids have several advantages over many of the currently available bhr vectors in that: (i) they are relatively small (< 5.3 kb), (ii) they possess an extended multiple cloning site (MCS), (iii) they allow direct selection of recombinant plasmid molecules in Escherichia coli via disruption of the LacZ alpha peptide, (iv) they are mobilizable when the RK2 transfer functions are provided in trans and (v) they are compatible with IncP, IncQ and IncW group plasmids, as well as with ColE1- and P15a-based replicons.

Bacteria↗

PubMed1995

Diffusion of innovation II: Formulary acceptance rates of new drugs in teaching and non-teaching British Columbia hospitals--a drug development perspective.

Diffusion theory was used to examine differences in adoption rates of new drugs by British Columbia teaching and non-teaching hospitals. Surveys were mailed in September 1990 to 41 hospital pharmacies (response rate = 88%), requesting hospital pharmacy directors to provide formulary inclusion dates of 29 study drugs marketed between July 1987 and March 1990. Of the 36 initial responses, 31 were suitable for further analysis and these were surveyed again in April 1993 (response rate = 100%) as to the formulary status of drugs not initially approved. The second survey ensured that all study drugs would have at least 36 months on the Canadian market when determining formulary acceptance times. Of the 29 study drugs, six were not approved for use in any of the 31 study hospitals. The six teaching hospitals had a median formulary approval time of 8.0 months compared to 12.8 months in the 25 non-teaching hospitals for the 23 study drugs. Although 21 of 23 study drugs were approved for use earlier in teaching hospitals than non-teaching hospitals, only alfentanil was found to be adopted significantly earlier (U = 11, n1 = 5, n2 = 19, alpha = 0.05). Variations in formulary approval times for new drugs have a bearing on patient care, Pharmacy and Therapeutics Committees, hospital budgets, and pharmaceutical firm revenues.

British Columbia↗

PubMed1994

Exponential smoothing method for forecasting drug expenditures.

A model for forecasting a hospital pharmacy drug budget is described, and its results in 10 hospital pharmacy departments are evaluated. A model for forecasting inpatient drug expenditures was developed based on the method of exponential smoothing. Exponential smoothing predicts a value based on the forecast for the prior period, with adjustment for the error of that forecast. Recent data are weighted more heavily than older data; as data become older, weights decline exponentially. The model incorporates changes in workload in addition to drug expenditure data. The variable used for workload can vary from one hospital to another, depending on the statistics that are available. The model was designed to be more accurate than current methods, easy and quick to use, and usable with a minimal knowledge of statistics and forecasting theory. The model was tested on fiscal 1988-1992 drug budget data from 10 British Columbia hospital pharmacy departments. Four departments had insufficient data; of the remaining six, the forecasting model performed better than the hospitals' current methods in four departments. The mean absolute deviation between budgeted (by current methods) and actual drug expenditures was 8.70% (range, 6.19-15.16%). The forecasting model yielded a mean absolute deviation of 5.93% (range, 3.13-7.66%). Better forecasts resulted when pharmacy medication-order volume was used as a workload variable, as compared with hospital inpatient days. An exponential smoothing model improved the accuracy of drug-budget forecasts in four of six pharmacy departments.

British Columbia↗

PubMed1994

Possible antiestrogenic properties of chloro-s-triazines in rat uterus.

Several published reports have indicated that certain chloro-s-triazine herbicides may alter endocrine function in rats, possibly by androgen receptor binding. In direct tests of estrogenic bioactivity, oral doses of up to 300 mg/kg/d of atrazine, simazine, or the common metabolite diaminochlorotriazine (DACT) did not significantly increase uterine weight of ovariectomized Sprague-Dawley female rats. The highest dose, which was approximately 10% of the LD50 for these compounds, did cause body weight loss. When administered concomitantly with sc injections of estradiol (2 micrograms/kg), 300 mg/kg of orally administered chlorotriazines significantly reduced uterine weight in comparison to animals given estrogen alone. Neither atrazine, simazine, nor DACT, at oral doses up to 300 mg/kg/d, stimulated incorporation of [3H]thymidine into uterine DNA of immature Sprague-Dawley female rats. However, oral treatment at doses of 50 mg/kg and higher significantly reduced thymidine incorporation into uterine DNA extracted from immature rats given a single injection of 0.15 microgram estradiol. Oral doses of 300 mg/kg of atrazine, simazine, or DACT significantly reduced expression of progesterone receptor binding in cytosol fractions prepared from uteri of ovariectomized rats injected sc with 1 microgram estradiol; 50 mg/kg triazine was not effective in this case. Uterine progesterone receptor levels were not stimulated in rats given oral doses up to 300 mg/kg of these triazines without estradiol injections. These results suggest that atrazine, simazine, and DACT possess no intrinsic estrogenic activity but that they are capable of weak inhibition of estrogen-stimulated responses in the rat uterus. This inhibition may play a role in the previously observed disruptive actions of chlorotriazines on reproductive endocrine function of female rats.

Administration, Oral↗

PubMed1994

Chloro-s-triazine antagonism of estrogen action: limited interaction with estrogen receptor binding.

In an accompanying article (see pp. 183-196), it was reported that administration of very high doses of the chlorotriazine herbicides atrazine, simazine, and diaminochlorotriazine (DACT), a common metabolite, expressed antiestrogenic activity in uteri of female Sprague-Dawley rats without expressing intrinsic estrogenic activity. In the present article, studies of chlorotriazine interaction with rat uterine estrogen receptors (ER) are reported. Under equilibrium conditions, none of the triazine compounds showed an ability to compete against binding of radiolabeled estradiol to ER. A weak competition was evident only if cytosols were preincubated with triazines at 25 degrees C prior to introduction of tracer. Competition was very weak, with kl estimates of 10-100 microM. A limited Scatchard analysis suggested a competitive type of inhibition. Sucrose gradient analysis of cytosol incubations showed that triazine interaction with the 4S isoform of ER may be greater than with the 8S form. When administered to ovariectomized rats for 2 d at 300 mg/kg/d, atrazine, simazine, or DACT all reduced uterine ER binding capacity by approximately 30%. Results from the receptor binding studies indicated that triazine competition against ER binding occurred to a much lesser degree than inhibition of estrogen-mediated responses reported in accompanying articles. This suggests that the complete responses to triazines may include inhibition of events other than or in addition to ER binding of estrogen.

Animals↗

PubMed1994

Diffusion of innovation I: Formulary acceptance rates of new drugs in teaching and non-teaching British Columbia hospitals--a hospital pharmacy perspective.

Lag times in the diffusion of new drugs in the hospital setting have both patient care and pharmaceutical industry implications. This two-part series uses diffusion theory to examine differences in the adoption rates of new drugs in British Columbia teaching and non-teaching hospitals. Formulary addition of a new drug by a hospital's Pharmacy and Therapeutics Committee was considered the adoption indicator. Time for adoption was defined as the difference between a drug's Canadian market approval date and the date of formulary addition. Surveys were mailed in September 1990 to 41 hospital pharmacies (response rate = 88%), asking respondents to provide formulary inclusion dates of 29 drugs marketed between July 1987 and March 1990. A significant difference (Mann-Whitney U Test, p < 0.0358) in median adoption time was observed between the six teaching and 25 non-teaching study hospitals, with the former adopting a new drug in 7.5 months versus the latter adopting a new drug in 12.1 months.

British Columbia↗

PubMed1993

Delta retinoic acid receptor isoform delta 1 is distinguished by its exceptional N-terminal sequence and abundance in the limb regeneration blastema.

In amphibian limb regeneration memory for position in the proximal-distal axis can be respecified by retinoic acid. The favoured candidates to mediate this effect are the retinoic acid receptors (RARs) and of the RARs identified in the regeneration blastema, the delta receptor is the most abundant. The presence in blastemal mesenchyme of at least two delta receptor isoforms, delta 1 and delta 2, alternatively spliced at the A-B junction, was demonstrated in expression studies and by PCR cloning. The delta 1 receptor is abundant in regenerative structures such as the limb and tail, whereas the delta 2 and alpha receptors show a more uniform pattern of expression across adult newt tissues. Full-length cloning of the delta 1 receptor established the presence of an unusually long open reading frame and N-terminal sequence that appears unique among vertebrate retinoic acid receptors. Transient transfection of expression constructs into COS cells followed by Western blotting confirmed the existence of at least three potential initiation sites for delta 1 translation. The possibility that delta 1 RAR expression may specify positional memory directly was tested in RNase protection experiments. delta 1 receptor message is increased on amputation, but does not exhibit a pronounced differential distribution along the proximal-distal axis in normal and regenerating limbs, nor does it show a persistent alteration in expression levels following a dose of retinoic acid sufficient to respecify position. The possibility that the morphogenetic effects of RA may be mediated through receptor interactions is raised by the finding that single mesenchymal blastemal cells in culture can express multiple RAR subtypes (delta 1 and alpha) and isoforms (delta 1 and delta 2).

Amino Acid Sequence↗