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Biomedical subjects

D Jenkins

Publications and source records attributed to D Jenkins.

At least 37 records · Page 2Linked to original sources
PubMed2001

Evidence for an inflammatory pathophysiology in idiopathic rhinitis.

BACKGROUND: The pathophysiology of idiopathic rhinitis is unknown but the disease is classified as being non-allergic on the basis of negative serum IgE radioallergosorbent assay (RAST) and skin prick tests. In contrast, allergic rhinitis has a Th2 type inflammatory pathology mediated by IgE and mast cells. OBJECTIVE: To test the null hypothesis that there would be no difference in the cellular infiltrate for key Th2-associated inflammatory cells between allergic and idiopathic rhinitis. METHODS: We applied strict selection criteria in the recruitment of allergic and idiopathic rhinitis cases. In contrast to previous studies which used cytology or small biopsies, we studied all layers of the mucosa by using whole, full-thickness nasal turbinate specimens with an average length of 2.5 cm. Immunohistochemistry and in situ hybridization techniques were used to compare the distribution and cell populations of mast cells, IgE positive (IgE+) cells, eosinophils and plasma cells in perennial allergic (n = 11) and idiopathic (n = 17) rhinitis, and control nasal mucosal tissue (n = 9). RESULTS: Mast cells and IgE+ cells were significantly increased within the epithelium of allergic and idiopathic mucosa compared to normal mucosa (P < 0.05). More IgE+ cells were present in the allergic group compared to the idiopathic group with the majority of IgE+ cells being mast cells. Both rhinitic groups showed increased eosinophilia localized to the superficial submucosa compared to normal mucosa (P < 0.05). More plasma cells were present in the allergic rhinitic tissue. CONCLUSION: Idiopathic and allergic rhinitic mucosa show similarities in their inflammatory infiltrate suggesting that both groups share a highly localized Th2, IgE-mediated cellular immunopathology.

Adolescent↗
PubMed2001

A review of evaluative studies of computer-based learning in nursing education.

Although there have been numerous attempts to evaluate the learning benefits of computer-based learning (CBL) packages in nursing education, the results obtained have been equivocal. A literature search conducted for this review found 25 reports of the evaluation of nursing CBL packages since 1966. Detailed analysis of the evaluation methods used in these reports revealed that most had significant design flaws, including the use of too small a sample group, the lack of a control group, etc. Because of this, the conclusions reached were not always valid. More effort is required in the design of future evaluation studies of nursing CBL packages.

Computer-Assisted Instruction↗
PubMed2001

Diagnosing human papillomaviruses: recent advances.

The biological importance of a group of human papillomaviruses, known as high-risk human papillomaviruses, as the key causal agent for almost all cervical cancer has now been established. Many aspects of the natural history of high-risk human papillomaviruses as sexually transmitted infections and as oncogenic agents have been researched. Although human papillomavirus diagnosis is largely confined to DNA detection techniques in cervical smears, there is accumulating evidence that the best polymerase chain reaction and hybrid capture techniques are more sensitive and probably of similar specificity compared with cervical cytology as a triage test for women with borderline smear abnormalities and for screening older women. This is strong presumptive evidence that high-risk human papillomavirus testing could be useful in cervical screening. Current research is aimed at establishing a place for high-risk human papillomavirus testing in routine screening practice. Randomised clinical trials, long-term natural history studies, mathematical modelling, and economic and psychosocial studies are being used to demonstrate whether this testing can improve both the effectiveness and efficiency of cervical screening in a range of situations.

Female↗
PubMed2001

The effect of lower-extremity position on cerebrospinal fluid pressures.

OBJECTIVE: To determine the effects of lower-extremity positioning on cerebrospinal fluid opening pressure (CSFp). The authors believed that during lumbar puncture (LP), CSFp does not meaningfully decrease when the lower extremities are extended from flexion, as is often suggested. METHODS: In a convenience sample of adult patients who clinically required LP in an urban emergency department, three sequential CSFp measurements were obtained in either sequence A (knee, hip, and neck flexion [90 degrees ], then extension, then flexion) or sequence B (extension, flexion, then extension) prior to CSF withdrawal. The neck was flexed at 30 degrees when the lower extremities were flexed, while the thoracolumbar spine was kept in the neutral position for all measurements. RESULTS: Nineteen patients were studied in each sequence. Although variable, overall within-patient changes between positions were not clinically meaningful. Mean and 95% confidence intervals (95% CIs) for the decrease in CSFp from position 1 to position 3 (same position) were 0.2 cm H(2)O (1.7%) and 0.9 to -0.6 cm H(2)O (6% to -2.7%), respectively. Changing from flexion to extension decreased pressure measurements by a mean of 0.9 cm H(2)O (2.5%) [95% CI = 2.1 to -0.1 cm H(2)O (7.6% to -2.4%)]. Changing from extension to flexion increased CSFp by a mean of 1.1 cm H(2)O (6.1%) [95% CI = 0.2 to 2.0 cm H(2)O (1.3% to 11.5%)], a statistically but not clinically meaningful change. CONCLUSIONS: Changing lower-extremity position did not meaningfully change mean CSFp. These data do not support the common suggestion that extending the lower extremities during LP meaningfully decreases CSF opening pressures.

Adolescent↗
PubMed2001

Beta-hydroxy-beta-methylbutyrate (HMB) supplementation does not affect changes in strength or body composition during resistance training in trained men.

This investigation evaluated the effects of oral beta-hydroxy-beta-methylbutyrate (HMB) supplementation on training responses in resistance-trained male athletes who were randomly administered HMB in standard encapsulation (SH), HMB in time release capsule (TRH), or placebo (P) in a double-blind fashion. Subjects ingested 3 g x day(-1) of HMB or placebo for 6 weeks. Tests were conducted pre-supplementation and following 3 and 6 weeks of supplementation. The testing battery assessed body mass, body composition (using dual energy x-ray absorptiometry), and 3-repetition maximum isoinertial strength, plus biochemical parameters, including markers of muscle damage and muscle protein turnover. While the training and dietary intervention of the investigation resulted in significant strength gains (p < .001) and an increase in total lean mass (p = .01), HMB administration had no influence on these variables. Likewise, biochemical markers of muscle protein turnover and muscle damage were also unaffected by HMB supplementation. The data indicate that 6 weeks of HMB supplementation in either SH or TRH form does not influence changes in strength and body composition in response to resistance training in strength-trained athletes.

Adult↗
PubMed2001

Short-term beta-hydroxy-beta-methylbutyrate supplementation does not reduce symptoms of eccentric muscle damage.

PURPOSE: We examined the effects of short-term beta-hydroxy-beta-methylbutyrate (HMB) supplementation on symptoms of muscle damage following an acute bout of eccentric exercise. METHODS: Non-resistance trained subjects were randomly assigned to a HMB supplement group (HMB, 40mg/kg bodyweight/day, n = 8) or placebo group (CON, n = 9). Supplementation commenced 6 days prior to a bout of 24 maximal isokinetic eccentric contractions of the elbow flexors and continued throughout post-testing. Muscle soreness, upper arm girth, and torque measures were assessed pre-exercise, 15 min post-exercise, and 1, 2, 3, 4, 7, and 10 days post-exercise. RESULTS: No pre-test differences between HMB and CON groups were identified, and both performed a similar amount of eccentric work during the main eccentric exercise bout (p > .05). HMB supplementation had no effect on swelling, muscle soreness, or torque following the damaging eccentric exercise bout (p > .05). CONCLUSION: Compared to a placebo condition, short-term supplementation with 40mg/kg bodyweight/day of HMB had no beneficial effect on a range of symptoms associated with eccentric muscle damage. If HMB can produce an ergogenic response, a longer preexercise supplementation period may be necessary.

Adult↗
PubMed2001

Unique gene expression patterns in liver and kidney associated with exposure to chemical toxicants.

DNA arrays containing 260 unique genes involved in phase I and II metabolism, heat shock, DNA repair, inflammation, transcription, and housekeeping were used to examine gene expression patterns in liver and kidney in response to five classes of chemicals (polyaromatic hydrocarbons: benzo(a)pyrene, 3-methylcholanthrene; DNA alkylators: dimethylnitrosamine, ethylnitrosourea; peroxisome proliferators: diethylhexylphthalate, clofibrate; heavy metals: CdCl(2), HgCl(2); and oxidative stressors: CCl(4), bromobenzene). Time course experiments in mice were carried out in both tissues for each chemical and dose-response studies were used to further evaluate several of these chemicals. Each pair of chemicals yielded a similar pattern of gene expression distinct from the other four classes of chemicals. Both peroxisome proliferators up-regulated Cyp4a10, acyl-CoA thioesterase, and insulin-like growth factor binding protein-1, whereas the DNA alkylators altered the expression of monokine induced by gamma-interferon, the metallothioneins, p21, and several acute phase proteins. For each of the five classes of chemicals tested, several genes that were induced or repressed were common in each chemical exposure, whereas other genes were unique for that specific class of compound. Both time and dose are important factors in differentiating between chemical classes. Likewise, comparison of changes in messenger RNA expression between the kidney and liver of treated animals indicates that gene arrays may be useful in determining the comparative toxicity of chemicals in various tissues but that exposure to uncharacterized chemicals will have to be monitored in several tissues.

Alkylating Agents↗
PubMed2001

Microbial storage products, biomass density, and settling properties of enhanced biological phosphorus removal activated sludge.

The relationships between bacterial storage products, density, and settling characteristics were determined in a laboratory-scale sequencing batch reactor (SBR) enhanced biological phosphorus removal (EBPR) system. Both long-term and single anaerobic-aerobic cycle variations in these properties were studied. Increased polyphosphate (PP) content of the biomass during long-term operation resulted in improved sludge volume index (SVI) values. End-aerobic phase (after phosphate (P) uptake) SVI values were consistently lower than end-anaerobic phase (after P release) values. Neither filamentous nor slime bulking were evident by microscopic observations. Biomass density increased at a rate of 1.2 mg/L per each 1% increase in biomass P content. End-aerobic phase samples had an average 25% higher buoyant density than end-anaerobic phase samples; which was attributed to aerobic P uptake. Biomass density was negatively correlated with SVI values, and SVI values increased sharply at low biomass density. A mathematical model developed by Mas et al. (1985) was modified to predict total cell density based on literature values of PP, glycogen (GLY), and poly-b-hydroxybutyrate (PHB) densities. Model predictions were in good agreement with experimental results, although improved measurement of PP density is required to improve model predictions.

Bacteria, Aerobic↗
PubMed2001

From data to knowledge--the Visible Human Project continues.

The U. S. National Library of Medicine (NLM) has long been a world leader in the archiving and distribution of the print-based images of biology and medicine. NLM has also been a pioneer in the use of computer systems to encode and distribute textual knowledge of the life sciences. NLM's Long Range Planning effort of 1985-86 foresaw a coming era where NLM's Bibliographic and factual database services would be complemented by libraries of digital images, distributed over high speed computer networks. The NLM Planning Panel on Electronic Imaging recommended that NLM should undertake the building a digital image library consisting of computerized tomography (CT) and magnetic resonance (MR) images, and cryosection images of a representative, carefully selected and prepared male and female cadaver--the "Visible Human Project ." The male and female Visible Human data sets are now being made available through a license agreement with the NLM. The data sets are supporting a wide range of educational, diagnostic, treatment planning, and commercial uses. The NLM, in partnership with other U.S. government research agencies has begun a three prong effort within the Visible Human Project to address: the creation of a new online, interactive, digital head-and-neck atlas; the development of a tool kit of computational programs capable of automatically performing many of the basic data handling functions required for using Visible Human data in applications; and the improved resolution of future Visible Human data sets through the reduction of the anatomical artifacts introduced by the methods used to stabilize and section the anatomical materials and the development of staining and wide-spectrum methods for increasing tissue contrast.

Anatomy, Artistic↗
PubMed2000

Design and SAR of novel potassium channel openers targeted for urge urinary incontinence. 1. N-Cyanoguanidine bioisosteres possessing in vivo bladder selectivity.

A structurally novel series of adenosine 5'-triphosphate-sensitive potassium (K(ATP)) channel openers is described. As part of our efforts directed toward identifying novel, bladder-selective potassium channel openers (KCOs) targeted for urge urinary incontinence (UUI), we found that bioisosteric replacement of the N-cyanoguanidine moiety of pinacidil (1, Figure 1) with a diaminocyclobutenedione template afforded squaric acid analogue 2, the prototype of a novel series of K(ATP) channel openers with unique selectivity for bladder smooth muscle in vivo. Further modification of the heterocyclic ring to give substituted aryl derivatives (3) afforded potent KCOs that possessed the desired detrusor selectivity when administered orally. The effects of these potassium channel agonists on bladder contractile function was studied in vitro using isolated rat detrusor strips. Potent relaxants were evaluated in vivo in a rat model of bladder instability. Lead compounds were evaluated concomitantly in normotensive rats for their effects on mean arterial blood pressure (MAP) and heart rate as a measure of in vivo bladder selectivity. (R)-4-[3,4-Dioxo-2-(1,2, 2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethyl-benzo nitrile (79) met our potency and selectivity criteria and represents an attractive development candidate for the treatment of UUI. Electrophysiological studies using isolated rat bladder detrusor myocytes have demonstrated that compound 79 produces significant hyperpolarization which is glyburide-reversed, thus consistent with the activation of K(ATP). The design, synthesis, structure-activity relationships (SAR), and pharmacological activity associated with this series of novel KCOs will be discussed.

Adenosine Triphosphate↗
PubMed2000

Differential levels of granzyme B, regulatory cytokines, and apoptosis in Crohn's disease and ulcerative colitis at first presentation.

The mechanisms of tissue damage in ulcerative colitis and Crohn's disease may reflect disordered humoral or cell-mediated effector mechanisms, respectively. Mucosal biopsies from untreated inflammatory bowel disease patients and normal controls were analysed for the expression of granzyme B, a cytotoxic effector molecule specifically associated with cell-mediated immunity, and for regulatory cytokines. Messenger RNA (mRNA) was analysed by reverse transcription-polymerase chain reaction and enzyme-linked oligonucleotide chemiluminescence assay. Mucosal biopsies were analysed by immunohistochemistry for granzyme B protein and lymphocyte markers and for the presence of apoptotic cells by terminal deoxynucleotidyl transferase end labelling. Granzyme B mRNA was elevated in Crohn's disease, but not in ulcerative colitis or control mucosal biopsies. Granzyme B mRNA levels correlated with interferon gamma mRNA levels in Crohn's disease. Granzyme B was expressed in CD3+, CD8+ T cells in the lamina propria of Crohn's disease mucosa and there were significantly more apoptotic cells in the lamina propria in Crohn's disease. In conclusion, granzyme B-expressing T lymphocytes are present in the focal mucosal lesions of Crohn's disease, together with spatially related apoptotic cell death. These results support the hypothesis that T-cell-mediated cytotoxic effector mechanisms may play a role in Crohn's disease.

Adolescent↗
PubMed2000

Decreased synthesis and expression of TGF-beta1, beta2, and beta3 in epithelium of HPV 16-positive cervical precancer: a study by microdissection, quantitative RT-PCR, and immunocytochemistry.

Cervical carcinogenesis is a multistep process initiated by 'high-risk' human papillomaviruses (HR-HPVs), most commonly HPV 16. Transforming growth factor-beta (TGF-beta) inhibits epithelial proliferation and down-regulates transcription of E6/E7 genes of HPV. Altered TGF-beta expression may be important in carcinogenesis. Quantitative RT-PCR was used to investigate TGF-beta1, beta2, and beta3 mRNA levels in nine specimens of normal cervix and 15 cervical precancers (eight HPV-positive, including five HPV 16-positive). Immunocytochemical expression of TGF-beta1, beta2, and beta3 was examined in cervical intraepithelial neoplasia (CIN) positive for HPV 16 (26), and in HPV-negative, normal ectocervical epithelium (9); reserve cell hyperplasia (12); and immature (7) and mature (15) squamous metaplasia. The intensity of staining for TGF-beta1 was measured using grey-scale image analysis. Microdissection was used to investigate epithelial and stromal (excluding crypts) levels of TGF-beta1 mRNA in HPV 16-positive cervical precancer. Normal cervix, including reserve cells and immature and mature metaplasia, showed strong immunocytochemical expression of all TGF-beta isoforms. Expression was decreased in the basal third of the epithelium in CIN 1, in the basal and middle thirds in CIN 2, and in all layers in CIN 3. Quantitative analysis of TGF-beta1 expression showed that the changes in CIN compared with normal ectocervix and mature metaplasia were statistically highly significant (p<0.001, ANOVA). TGF-beta1, beta2, and beta3 mRNA levels showed a significant decrease only in the five HPV 16-positive CIN samples when compared with normal (p=0. 0034, 0.0033, and 0.029, respectively). TGF-beta mRNA levels in HPV 16-positive epithelium also decreased from normal through low-grade to high-grade precancer. Stromal TGF-beta1 was absent or very low compared with epithelial production and was not altered in HPV 16 precancer. Progressive loss of epithelial TGF-beta expression and synthesis may be important in HPV 16-associated human cervical carcinogenesis.

Epithelium↗
PubMed2000

The effects of a repeated bout of eccentric exercise on indices of muscle damage and delayed onset muscle soreness.

This study examined markers of muscle damage following a repeated bout of maximal isokinetic eccentric exercise performed prior to full recovery from a previous bout. Twenty non-resistance trained volunteers were randomly assigned to a control (CON, n=10) or experimental (EXP, n=10) group. Both groups performed 36 maximal isokinetic eccentric contractions of the elbow flexors of the non-dominant arm (ECC1). The EXP group repeated the same eccentric exercise bout two days later (ECC2). Total work and peak eccentric torque were recorded during each set of ECC1 and ECC2. Isometric torque, delayed onset muscle soreness (DOMS), flexed elbow angle and plasma creatine kinase (CK) activity were measured prior to and immediately following ECC1 and ECC2. at 24h intervals for 7 days following ECC1 and finally on day 11. In both groups, all dependent variables changed significantly during the 2 days following ECC1. A further acute post-exercise impairment in isometric torque (30 +/- 5%) and flexed elbow angle (20 +/- 4%) was observed following ECC2 (p<0.05), despite EXP subjects producing uniformly lower work and peak eccentric torque values during ECC2 (p<0.05). No other significant differences between the CON and EXP groups were observed throughout the study (p>0.05). These findings suggest that when maximal isokinetic eccentric exercise is repeated two days after experiencing of contraction-induced muscle damage, the recovery time course is not significantly altered.

Adult↗
PubMed2000

Structure-function relations in the human placenta.

The human haemochorial placenta is a complex and dynamic interface between embryonic and maternal tissues. A myriad array of compounds has been identified at this interface, some of which exert local effects which might be important in maintaining the integrity of the organ. These compounds are diverse in nature and function; they include enzymes, hormones and bioactive peptides. Successful nidation requires the synchronization of endometrial maturation and embryonic development. The complex nature of this interface requires the application of sound sampling strategies. The new stereological methods have thrown fresh light on the growth and development of the human placenta. These methods permit the objective, quantitative description of morphology by efficient design-based methods. This approach has permitted a better definition of the functional morphology of the placenta. Applications of these methodologies are providing a spatial and temporal framework on which to lay the new physiological and molecular information. Here we review the essential features of the stereological approach, identify useful structural quantities and provide some examples of their application. The problems associated with the quantification of immunocytochemistry are illustrated with the use of immunoreactivity to insulin-like growth factor I receptor in normal placentae and in pre-eclampsia. Although stereology can provide useful quantitative information about the structure of this dynamic tissue, other anatomical methods that could be applied to better define the relationships between structure and function will be discussed. These include confocal microscopy, to examine the dynamic physiological interactions of the different tissue compartments, and low-temperature electron microscopy techniques such as cryosubstitution, to allow better access to the biochemical information resident in the tissue. The complex and dynamic nature of the tissue requires a multidisciplinary approach; central to these investigations is a comprehensive understanding of its fine structure.

Estradiol↗
PubMed2000

Genetic analysis of insulin-like growth factor II and HLA-G in pre-eclampsia.

Pre-eclampsia (PE) is uniquely a disease of pregnancy and is the major cause of foetal and maternal morbidity and mortality. Epidemiological studies show that PE is highly heritable, with a high incidence in all populations. The underlying pathology indicates that absent or shallow invasion of foetal trophoblasts into maternal arteries is a feature of true PE. The objective of this study was to determine the genetic factors influencing PE. A large number of mother-father-baby trios were collected in which the first pregnancy was complicated by severe PE. After careful examination of the epidemiology and pathology of the disease, two plausible candidate genes, namely insulin-like growth factor II (IGF-II) and HLA-G, were analysed for association with PE. No association was found between a commonly occurring polymorphism in IGF-II and PE. Three polymorphisms in HLA-G were analysed in the sample cohorts. No association was found between three polymorphisms in HLA-G and PE. However, the frequency of the HLA-G insertion/deletion polymorphism in exon 8 deviated significantly from Hardy-Weinberg expectations in PE off-spring, reflecting an excess of heterozygotes for these polymorphisms in PE offspring. The significance of this deviation is not clear and further genetic analysis will be necessary to confirm this finding and to explore further the candidacy of HLA-G in PE.

Adult↗
PubMed2000

Idiopathic and allergic rhinitis show a similar inflammatory response

HYPOTHESIS: Idiopathic and allergic rhinitics have similar mucosal mast cell and IgE+ cell distribution. INTRODUCTION: The pathophysiology of idiopathic rhinitis (IR) is unknown but patients differ from those with allergic rhinitis (AR) in that they do not express IgE. Our study is novel because we investigated: (1) three study groups chosen prospectively using strict selection criteria over a 4-year period; and (2) mast cell and IgE+ cell counts were on full-thickness, full-length inferior turbinate mucosa. METHODS: Patient groups: allergic (n = 17); idiopathic: (n = 16); and normal controls (n = 9). Immunohistochemistry: mast cell and IgE+ cell detection using anti-mast cell tryptase and anti-IgE antibodies with an avidin-biotin (peroxidase) complex on paraffin processed tissue. Morphometry: sections were divided into three strata comprising an epithelial layer and two submucosal layers. Statistics: Mann-Whitney non-parametric analysis. alpha = 0.05, beta = 0.2. RESULTS: The power of the study was 89%. Mast cells (P = 0.03) and IgE+ cells (P < 0.05) were significantly increased in the epithelium of idiopahtic and allergic rhinitis mucosa compared to the normal control. More IgE+ cells were counted in the AR and IR groups compared to the controls in all three strata. CONCLUSION: Mast cells and IgE+ cells are involved in the pahtophysiology of IR. We propose that IR may be a variant form of AR involving a localized IgE-mediated inflammatory response.

Journal Article↗