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Biomedical subjects

J Young

Publications and source records attributed to J Young.

At least 127 records · Page 7Linked to original sources
PubMed2000

Vascular reactivity in acromegalic patients: preliminary evidence for regional endothelial dysfunction and increased sympathetic vasoconstriction.

BACKGROUND AND OBJECTIVES: Hypertension is found in one-third of acromegalic patients. An heterogenous distribution of cardiac output has been recently demonstrated in acromegalic patients with an increased blood flow at the level of the upper limb, suggesting that acromegalic patients may have some degree of endothelial dysfunction. Elsewhere, studies involving hypopituitary GH-deficient adults have shown that GH and/or IGF-I may have direct effect on endothelial function. SUBJECTS AND METHODS: We thus compared cutaneous vasoreactivity responses in 10 normotensive patients with active acromegaly (A) (six women and four men) aged 25-59 (mean, 43.2 years), whose basal GH and IGF-I levels ranged from 7.4 to 158 mU/l and from 401 to 1690 microg/l, respectively, and in 10 normal age- and sex-matched controls (NC) by means of Laser Doppler flowmetry at the levels of the palm and the dorsum of the right hand. Circulatory skin velocities were studied basally and after increasing skin temperature to 44 degrees C (in order to study direct nonspecific vasodilatation response which is independent of endothelial or autonomous nervous system and reflects normal vascular muscle function), after shear-stress (known to produce flow-dependent vasodilatation, mediated by nitric oxyde (NO) originating from endothelial cells) and after cold-stress applied on the opposite hand (known to produce vaso-constriction mediated by the sympathetic nervous system). RESULTS: The warm test induced a significant (P<0.001) and similar increase in both dorsal and palmar skin perfusion in A (mean +/- SD) (240+/-96 and 238+/-134%, respectively) and NC (232+/-137 and 233+/-73, respectively). Ischaemia release induced a significant increase in both dorsal and palmar skin blood flows in the two groups (P<0.001), but reactivities in acromegalic patients were about one half of those measured in controls (22.9+/-16.2% (A) vs. 46.9 25% (NC), 2P<0.02, at the level of the dorsum; and 45.0+/-43.6% (A) vs. 104.7+/-40.1 (NC), 2P<0.01, at the level of the palm). Cold pressor test resulted in significant decreases in both cutaneous flows (P<0.01) in the two groups, with a larger vasoconstriction (that did not reach statistical significance) in acromegalic patients as compared with controls (P< 0.10). CONCLUSION: Vascular smooth cell ability to produce skin vasodilatation is normal but endothelium-dependent vasodilatation appears to be impaired while sympathetic-mediated vasoconstrictive response might be increased in acromegaly. This endothelial dysfunction may contribute to hypertension and represent a risk factor for cardiovascular complications in acromegaly.

Acromegaly↗
PubMed2000

Adenocarcinoma of colon differentiating as dome epithelium of gut-associated lymphoid tissue.

AIMS: An early adenocarcinoma of the ascending colon was confined to a mass of gut-associated lymphoid tissue (GALT). The first description of an adenocarcinoma of colon differentiating as dome epithelium is presented. METHODS AND RESULTS: A plaque-like carcinoma was identified opposite the ileocaecal valve in an asymptomatic 56-year-old man with a family history of colorectal cancer. Malignant epithelium was confined to a mass of GALT filling but limited to the submucosa. Characterization of the neoplasm was undertaken by means of mucin histochemistry, immunohistochemistry, electron microscopy and assessment of DNA microsatellite instability status. The malignant epithelium comprised well differentiated columnar cells with a microvillous brush border and expressing MUC1, but no goblet cells or expression of MUC2. The demonstration of focal clusters of intraepithelial B-lymphocytes supported the presence of functioning M-cells within the malignant neoplasm. The cancer was DNA microsatellite stable despite the finding of tumour infiltrating lymphocytes. CONCLUSIONS: There is evidence for the origin of colorectal neoplasia from dome epithelium in both experimental models and microreconstruction studies of early adenomas in nonpolypotic human colorectal mucosa. It is suggested that the lymphocyte-rich subset of colorectal cancer that expresses MUC1 but not MUC2 may be differentiating as dome epithelium of gut-associated lymphoid tissue.

Adenocarcinoma↗
PubMed2000

Hyperplastic polyps and DNA microsatellite unstable cancers of the colorectum.

Although the scientific and clinical rationale for classifying colorectal cancer according to mechanisms underlying genetic instability is well supported, little is known of the early morphogenesis of sporadic cancer showing high levels of DNA microsatellite instability (MSI-H). Evidence is accumulating that the traditional adenoma-carcinoma sequence may not apply to sporadic MSI-H colorectal cancer. The serrated pathway comprising hyperplastic polyps, mixed polyps and serrated adenomas may serve as the missing link. This review relates the recently described CpG island methylator phenotype (CIMP) to the serrated pathway. Two rate-limiting genetic steps may underlie the neoplastic pathway associated with CIMP. A transmembrane receptor expressed by pericryptal myofibroblasts (HPP1) may be implicated in the transition from normal to hyperplasia whereas inactivation of hMLH1 is responsible for the conversion of hyperplasia to dysplasia through loss of DNA mismatch repair. These mechanisms fit with clinical observations relating to sporadic MSI-H colorectal cancer, specifically proximal location, multiplicity, higher frequency among females and rapid evolution of early cancer.

Colonic Neoplasms↗
PubMed2000

Adjusting stroke patients' poor position: an observational study.

Although nurses' role in rehabilitation has been generally ill-defined and consistently undervalued, of all professional groups, nurses working with stroke patients have potentially the greatest contribution to make. Stroke patients are believed to benefit from good posture yet they can spend long periods in inappropriate positions. This study examined the positioning, handling and mobilizing of stroke patients in hospital. Non-participant observation was used to gather data on stroke patients' position and nurses' activities. This paper addresses two basic questions--what causes the adjustment of patients from poor to good position and who is involved in achieving this adjustment. Poor position was observed to end 158 times in 380 'patient hours' of observation. The most frequent causes of positional improvement were activities whose primary intention was unrelated to position correction. The deliberate adjustment of patients' position by nurses was a rare event which occupied a small part of nurses' time. The potential for a more considered and consistent nursing approach appears to be great.

Activities of Daily Living↗
PubMed2000

Nurses' perceptions of the nature and frequency of aggression in general ward settings and high dependency areas.

Studies on aggression in healthcare settings have reported increased frequency of this behaviour in both psychiatric and accident and emergency areas; however, to date, very few studies have addressed this issue in general ward settings in Australia. This descriptive study was conducted to determine nurses' perceptions of the nature and frequency of aggressive behaviours in general wards and high dependency areas and thereby address the gap in the literature. Two hundred and nine nurses in one Australian hospital completed a 23-item questionnaire on aggression in the workplace. The findings revealed that the majority (89.5%) of nurses defined aggressive behaviour as including verbal aggression, physical aggression and intimidation. Ninety-five per cent of respondents had encountered at least several episodes of verbal aggression within the last 12 months. Patients were found to be the main perpetrators of aggressive acts, followed by relatives. After experiencing either verbal or physical aggression nurses most frequently reported feeling angry or emotionally hurt. These findings confirm that acts of aggression are experienced frequently in the general medical and surgical ward areas of the study hospital. Consequently, there is a need to provide staff with education and support in order to deal with this issue and minimize the impact of increasing levels of aggression in the workplace.

Adaptation, Psychological↗
PubMed2000

Investigating recovery from stroke: a qualitative study.

A recent randomized controlled trial evaluated the effects of specialist nurses providing information, advice and support to caregivers and patients at home during the first year after a stroke. Reported here are the results of a complementary study which used qualitative methods to examine the experience of patients and caregivers during the year of recovery after a stroke. We used semi-structured interviews with a purposively selected sample of 30 patients and 15 caregivers at the end of a randomized controlled trial (13-16 months post-stroke). Patients and caregivers provided vivid descriptions of the recovery process. Recovery was perceived in terms of the degree of congruence patients identified between their lives before, and after, stroke. Patients therefore had individual and personal yardsticks for measuring their recovery. In conclusion, further research and interventions must consider the diverse, complex, dynamic and highly personal character of stroke recovery. Traditional outcome measures are too simplistic to capture patients' and caregivers' experiences. There do not appear to be single or simple solutions to the problems of facilitating psycho-social adjustment.

Aged↗
PubMed2000

Proteomic analysis of differential protein expression in primary hepatocytes induced by EGF, tumour necrosis factor alpha or the peroxisome proliferator nafenopin.

Peroxisome proliferators are nongenotoxic rodent-liver carcinogens that have been shown to cause both an induction of hepatocyte proliferation and a suppression of apoptosis. Both epidermal growth factor (EGF) and the peroxisome proliferator nafenopin induce DNA replication in primary rat hepatocyte cultures, but apparently through different signalling pathways. However, both EGF and nafenopin require tumour necrosis factor alpha (TNFalpha) signalling to induce DNA replication. By examining proteins isolated from rat primary hepatocyte cultures using two-dimensional gel electrophoresis and mass spectrometry, we found that proteins showing an altered expression pattern in response to nafenopin differed from those showing altered expression in response to EGF. However, many proteins showing altered expression upon stimulation with TNFalpha were common to both the EGF and nafenopin responses. These proteome profiling experiments contribute to a better understanding of the molecular mechanisms involved in the response to peroxisome proliferators. We found 32 proteins with altered expression upon stimulation with nafenopin, including muscarinic acetylcholine receptor 3, intermediate filament vimentin and the beta subunit of the ATP synthase. These nonperoxisomal protein targets offer insights into the mechanisms of peroxisome proliferator-induced carcinogenesis in rodents and provide opportunities to identify toxicological markers to facilitate early identification of nongenotoxic carcinogens.

Actins↗
PubMed2000

Physical characteristics of the ECAT EXACT3D positron tomograph.

The 'EXACT3D' positron tomograph, which is now in routine clinical research use, was developed with the aim of achieving unprecedented sensitivity, high spatial and temporal resolution and simplicity of design using proven detector technology. It consists of six rings of standard detector blocks (CTI/Siemens EXACT HR+) with 4.39 mm x 4.05 mm x 30 mm elements, giving an axial field of view (FOV) of 23.4 cm. This extended FOV and the absence of interplane septa and retractable transmission rod sources has allowed greatly simplified gantry and detector cassette design. Operation in exclusive 3D mode requires an alternative to the conventional coincidence method for transmission scanning, and a single photon approach using a hydraulically driven 137Cs point source has been implemented. The tomograph has no other moving parts. A single time frame of data without any compression is very large (> 300 Mbyte) and two approaches are employed to overcome this difficulty: (a) adjacent sinograms can be summed automatically into different combinations and (b) listmode (event-by-event) acquisition has been instituted, which is both storage efficient (particularly for acquisition of sparse data sets) and maximizes temporal resolution. The high-speed I/O and computing hardware can maintain a sustained acquisition rate of about 4 million coincidence events per second. A disadvantage of the large axial FOV in 3D is the increased sensitivity to activity outside the coincidence FOV. However, this can be minimized by additional side shielding. The mean spatial resolution is 4.8 +/- 0.2 mm FWHM (transaxial, 1 cm off-axis) and 5.6 +/- 0.5 mm (axial, on-axis). Its absolute efficiency is 5.8% for a line source in air (just spanning the axial FOV) and 10% for a central point source (with thresholds of 350-650 keV). For a uniform 20 cm diameter cylinder, the efficiency is 69 kcps kBq(-1) ml(-1) (after subtraction of a scatter fraction of 42%). Sensitivity relative to the EXACT HR+ (with four rings of blocks) is 2.5 (3D) and 12 (2D) times respectively. The rate of random events in blood flow studies in the brain and body, using 15O-labelled water, can be controlled by limiting the administered dose and inserting additional side shielding.

Cesium Radioisotopes↗
PubMed2000

On the evolution of misunderstandings about evolutionary psychology.

Some of the controversy surrounding evolutionary explanations of human behavior may be due to cognitive information-processing patterns that are themselves the result of evolutionary processes. Two such patterns are (1) the tendency to oversimplify information so as to reduce demand on cognitive resources and (2) our strong desire to generate predictability and stability from perceptions of the external world. For example, research on social stereotyping has found that people tend to focus automatically on simplified social-categorical information, to use such information when deciding how to behave, and to rely on such information even in the face of contradictory evidence. Similarly, an undying debate over nature vs. nurture is shaped by various data-reduction strategies that frequently oversimplify, and thus distort, the intent of the supporting arguments. This debate is also often marked by an assumption that either the nature or the nurture domain may be justifiably excluded at an explanatory level because one domain appears to operate in a sufficiently stable and predictable way for a particular argument. As a result, critiques in-veighed against evolutionary explanations of behavior often incorporate simplified--and erroneous--assumptions about either the mechanics of how evolution operates or the inevitable implications of evolution for understanding human behavior. The influences of these tendencies are applied to a discussion of the heritability of behavioral characteristics. It is suggested that the common view that Mendelian genetics can explain the heritability of complex behaviors, with a one-gene-one-trait process, is misguided. Complex behaviors are undoubtedly a product of a more complex interaction between genes and environment, ensuring that both nature and nurture must be accommodated in a yet-to-be-developed post-Mendelian model of genetic influence. As a result, current public perceptions of evolutionary explanations of behavior are handicapped by the lack of clear articulation of the relationship between inherited genes and manifest behavior.

Biological Evolution↗
PubMed2000

Expression of vascular endothelial growth factor in uveal melanoma and its correlation with metastasis.

AIMS: To evaluate the expression of vascular endothelial growth factor (VEGF) in uveal melanomas and correlate its presence with tumour characteristics and systemic metastasis. METHODS: 47 cases of ciliochoroidal melanoma enucleated between 1983 and 1993 were retrieved from the pathology archives at the University of Western Ontario. Paraffin sections stained with haematoxylin and eosin, periodic acid Schiff, and periodic acid Schiff without haematoxylin after bleaching of melanin were examined. The expression of VEGF protein was examined by an immunoalkaline phosphatase method following antigen retrieval, using an antibody to VEGF and vector red as the chromogen. The intensity of VEGF immunoreactivity was graded on a scale of 0-7 and correlated with tumour cell type, tumour size, presence or absence of necrosis, pigmentation, mitotic activity, microvascular density, and microvascular pattern. RESULTS: VEGF immunoreactivity was present in 44/47 tumours (94%): the intensity was graded as very weak (1-2) in 29/47 (62%) and as weak or greater in 15/47 (32%). VEGF was also found in the ciliary epithelium, smooth muscle of the ciliary body and iris, retinal ganglion cells, inner photoreceptor segments, and the retinal pigment epithelium. Follow up data were available in 43/47 patients (91.5%), with a median follow up time of 10 years. 16/43 (37%) patients developed metastases. VEGF expression in melanoma was linked to the presence of tumour necrosis and the degree of pigmentation but no statistically significant relation with microvascular pattern, tumour size, or microvascular density was found. There was no statistically significant correlation between VEGF expression and metastasis. CONCLUSIONS: Most ciliochoroidal melanomas express VEGF and expression is correlated with the presence of necrosis but not with the occurrence of systemic metastasis or tumour angiogenesis.

Adult↗
PubMed2000

Analysis of genetic and phenotypic heterogeneity in juvenile polyposis.

BACKGROUND: Juvenile polyposis syndrome (JPS) is characterised by gastrointestinal (GI) hamartomatous polyposis and an increased risk of GI malignancy. Juvenile polyps also occur in the Cowden (CS), Bannayan-Ruvalcaba-Riley (BRRS) and Gorlin (GS) syndromes. Diagnosing JPS can be problematic because it relies on exclusion of CS, BRRS, and GS. Germline mutations in the PTCH, PTEN and DPC4 (SMAD4) genes can cause GS, CS/BRRS, and JPS, respectively. AIMS: To examine the contribution of mutations in PTCH, PTEN, and DPC4 (SMAD4) to JPS. METHODS: Forty seven individuals from 15 families and nine apparently sporadic cases with JPS were screened for germline mutations in DPC4, PTEN, and PTCH. RESULTS: No patient had a mutation in PTEN or PTCH. Five different germline mutations were detected in DPC4; three of these were deletions, one a single base substitution creating a stop codon, and one a missense change. None of these patients had distinguishing clinical features. CONCLUSIONS: Mutations in PTEN and PTCH are unlikely to cause juvenile polyposis in the absence of clinical features indicative of CS, BRRS, or GS. A proportion of JPS patients harbour DPC4 mutations (21% in this study) but there remains uncharacterized genetic heterogeneity in JPS.

Adenomatous Polyposis Coli↗
PubMed2000

DNA microsatellite instability and mismatch repair protein loss in adenomas presenting in hereditary non-polyposis colorectal cancer.

BACKGROUND AND AIM: Hereditary non-polyposis colorectal cancer (HNPCC), as its name implies, is associated with few adenomas, and the early evolution of colorectal neoplasia is poorly understood. In this study our aim was to clarify the genetic profiles of benign polyps in subjects with HNPCC using a combined molecular and immunohistochemical approach. METHODS: Thirty adenomas and 17 hyperplastic polyps were obtained from 24 affected HNPCC subjects. DNA was extracted from paraffin embedded tissue by microdissection and analysed for the presence of microsatellite instability (MSI) and mutations in five genes known to be targets in mismatch repair deficiency (TGFbetaRII, IGF2R, BAX, hMSH3, and hMSH6). Serial sections were stained by immunohistochemistry for hMLH1 and hMSH2. RESULTS: Twenty four (80%) of 30 adenomas showed MSI. Of MSI positive adenomas, 66.7% showed MSI at more than 40% of markers (high level of MSI (MSI-H)). Two of 17 hyperplastic polyps revealed MSI at one marker (low level of MSI (MSI-L)). A significant association was found between MSI-H and high grade dysplasia in adenomas (p=0.004). Eight of nine adenomas with mutations of coding sequences revealed high grade dysplasia and all nine were MSI-H. Four of the nine ranged in size from 2 to 5 mm. The presence of the hMSH6 mutation was significantly correlated with high levels of MSI (80% of markers) (p<0.02). Twenty four adenomas gave evaluable results with immunohistochemistry. One of six (17%) microsatellite stable, six of seven (86%) MSI-L, and 11 of 11 (100%) MSI-H adenomas showed loss of either hMLH1 or hMSH2. CONCLUSIONS: Most adenomas in subjects with a definite diagnosis of HNPCC show MSI (80%). The finding of MSI-L is usually associated with loss of expression of hMLH1 or hMSH2, unlike the situation in MSI-L sporadic colorectal cancer. The transition from MSI-L to MSI-H correlated with the finding of high grade dysplasia and mutation of coding sequences and may be driven by mutation of secondary mutators such as hMSH3 and hMSH6. Advanced genetic changes may be present in adenomas of minute size.

Adenoma↗
PubMed2000

Neoplastic progression occurs through mutator pathways in hyperplastic polyposis of the colorectum.

AIM: Colorectal cancer has been described in association with hyperplastic polyposis but the mechanism underlying this observation is unknown. The aim of this study was to characterise foci of dysplasia developing in the polyps of subjects with hyperplastic polyposis on the basis of DNA microsatellite status and expression of the DNA mismatch repair proteins hMLH1, hMSH2, and hMSH6. MATERIALS AND METHODS: The material was derived from four patients with hyperplastic polyposis and between one and six synchronous colorectal cancers. Normal (four), hyperplastic (13), dysplastic (13), and malignant (11) samples were microdissected and a PCR based approach was used to identify mutations at 10 microsatellite loci, TGFbetaIIR, IGF2R, BAX, MSH3, and MSH6. Microsatellite instability-high (MSI-H) was diagnosed when 40% or more of the microsatellite loci showed mutational bandshifts. Serial sections were stained for hMLH1, hMSH2, and hMSH6. RESULTS: DNA microsatellite instability was found in 1/13 (8%) hyperplastic samples, in 7/13 (54%) dysplastic foci, and in 8/11 (73%) cancers. None of the MSI-low (MSI-L) samples (one hyperplastic, three dysplastic, two cancers) showed loss of hMLH1 expression. All four MSI-H dysplastic foci and six MSI-H cancers showed loss of hMLH1 expression. Loss of hMLH1 in MSI-H but not in MSI-L lesions showing dysplasia or cancer was significant (p<0.001, Fisher's exact test). Loss of hMSH6 occurred in one MSI-H cancer and one MSS focus of dysplasia which also showed loss of hMLH1 staining. CONCLUSION: Neoplastic changes in hyperplastic polyposis may occur within a hyperplastic polyp. Neoplasia may be driven by DNA instability that is present to a low (MSI-L) or high (MSI-H) degree. MSI-H but not MSI-L dysplastic foci are associated with loss of hMLH1 expression. At least two mutator pathways drive neoplasia in hyperplastic polyposis. The role of the hyperplastic polyp in the histogenesis of sporadic DNA microsatellite unstable colorectal cancer should be examined.

Aged↗
PubMed2000

Is dipalmitoylphosphatidylcholine a substrate for convertase?

Convertase has homology with carboxylesterases, but its substrate(s) is not known. Accordingly, we determined whether dipalmitoylphosphatidylcholine (DPPC), the major phospholipid in surfactant, was a substrate for convertase. We measured [(3)H]choline release during cycling of the heavy subtype containing [(3)H]choline-labeled DPPC with convertase, phospholipases A(2), B, C, and D, liver esterase, and elastase. Cycling with liver esterase or peanut or cabbage phospholipase D produced the characteristic profile of heavy and light peaks observed on cycling with convertase. In contrast, phospholipases A(2), B, and C and yeast phospholipase D produced a broad band of radioactivity across the gradient without distinct peaks. [(3)H]choline was released when natural surfactant containing [(3)H]choline-labeled DPPC was cycled with yeast phospholipase D but not with convertase or peanut and cabbage phospholipases D. Similarly, yeast phospholipase D hydrolyzed [(3)H]choline from [(3)H]choline-labeled DPPC after incubation in vitro, whereas convertase, liver esterase, or peanut and cabbage phospholipases D did not. Thus convertase, liver esterase, and plant phospholipases D did not hydrolyze choline from DPPC either on cycling or during incubation with enzyme in vitro. In conclusion, conversion of heavy to light subtype of surfactant by convertase may require a phospholipase D type hydrolysis of phospholipids, but the substrate in this reaction is not DPPC.

1,2-Dipalmitoylphosphatidylcholine↗