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Biomedical subjects

S Curran

Publications and source records attributed to S Curran.

At least 37 records · Page 2Linked to original sources

Morphologic stages of the equine embryo proper on days 17 to 40 after ovulation.

OBJECTIVE: To describe the gross and histologic changes that develop in the equine embryo proper (ie, the portion of the embryo that becomes the fetus) from days 17 to 40 after ovulation and to compare the external features of equine embryos with those of porcine, ovine, and human embryos. SAMPLE POPULATION: 34 embryos collected from mixed-breed pony mares. PROCEDURE: External features for each embryo proper, including length, number of branchial arches, growth of appendages, face and head features, and body features, were examined, using a dissecting microscope, for embryos collected on days 17 to 40. Internal features were histologically examined by serially sectioning embryos collected on days 20 to 35. RESULTS: Number of embryos recovered for each day ranged from 1 to 5. The initial detection of features was not related closely to age; typically, the first attainment of a given body length or characteristic varied over a 3-day period among embryos. Similarly, the period during which individual characteristics for a given Carnegie stage were attained ranged from 3 to 6 days. Age at first appearance of a characteristic was greater for equine embryos than ages reported for ovine and porcine embryos but less than for human embryos. Indicators of age included number of pairs of branchial arches, all limb buds present, retinal pigmentation, and prominence of the pontine flexure. CONCLUSIONS: No embryologic structures or changes were found that could be considered unique to equine embryos on days 17 to 40 after ovulation.

Animals↗

Cyclin D1 protein expression and gene polymorphism in colorectal cancer. Aberdeen Colorectal Initiative.

Cyclin D1 is a key cell cycle regulatory protein, the expression and subcellular localization of which is often altered in human tumor cells. A common A/G single nucleotide polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is associated with the presence of 2 distinct mRNA transcripts for this G1/S regulatory protein, and CCND1 genotype has been related to prognosis in lung cancer and head and neck carcinoma. We have investigated both the expression of cyclin D1 protein and the CCND1 A870G polymorphism in 100 colorectal cancer patients. Immunohistochemistry demonstrated cyclin D1 protein expression in 55% of tumors, and while the absence of cyclin D1 protein was not associated with outcome (p=0.81), high levels of protein expression (>50% of tumor cells expressing cyclin D1) correlated with significantly shortened overall survival (p=0.01). Using polymerase chain reaction restriction fragment length polymorphism analysis, we determined the frequency of each genotype and found that CCND1 genotype was not related to overall survival (p>0.05). In addition, genotype was unrelated to the level of expression and localization of cyclin D1 protein, as well as other key G1/S checkpoint proteins (p21, p27, p53, retinoblastoma) and tumor proliferation markers (proliferating cell nuclear antigen). However, higher levels of p27, and to a lesser extent p21, were associated with reduced cytoplasmic cyclin D1 protein (p=0.029 and p=0.054, respectively). In conclusion, we have demonstrated that high levels of cyclin D1 protein expression are related to outcome in colorectal cancer; however, the CCND1 A870G polymorphism is unrelated to either cyclin D1 protein expression or patient survival.

Adenocarcinoma↗

Hypescheme: an operational criteria checklist and minimum data set for molecular genetic studies of attention deficit and hyperactivity disorders.

Investigators engaged in mapping the genetic basis of attention deficit hyperactivity disorder (ADHD) currently use a number of measures for the collection of clinical information. This gives rise to difficulties in comparing datasets and research communications between independent groups. This paper describes the development of Hypescheme, which is an operational criteria checklist for ADHD, oppositional defiant disorder (ODD), and conduct disorder (CD), and is proposed as a minimum dataset for those engaged in molecular genetic studies of ADHD. Hypescheme consists of a computerised data checklist system that includes all the operational criteria required for both DSM-IV and ICD-10 diagnostic criteria and a systematic record of information about comorbid psychiatric, developmental, and neurological disorders. Using this data, an algorithm applies both DSM-IV and ICD-10 criteria to generate operational diagnostics under both these systems. Hypescheme is not designed to replace current assessment protocols but to be a final common checklist that can be completed by experienced researchers using all available data.

Attention Deficit Disorder with Hyperactivity↗

No association between low- and high-activity catecholamine-methyl-transferase (COMT) and attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children.

Biochemical and genetic studies of attention deficit hyperactivity disorder (ADHD) suggest that regulation of catecholamine neurotransmission is a key factor in the aetiology of the disorder. In particular, it is postulated that an underactive dopamine system is associated with the disorder. In this study we have tested this hypothesis by screening a clinical sample of Turkish children with the combined subtype of ADHD with a functional variant of catecholamine-methyl-transferase (COMT) that codes for high- and low-activity variants of the enzyme. Using within-family tests of association and linkage in a sample of 72 children, we found no evidence for a genetic association or linkage. We conclude that altered regulation of catecholamines due to this polymorphism does not have a significant main effect on the risk for ADHD in this population. However, it remains feasible that more minor effects or interacting effects with other genes or environment exist.

Alleles↗

Use of donepezil for the treatment of mild-moderate Alzheimer's disease: an audit of the assessment and treatment of patients in routine clinical practice.

There have been a number of randomised, placebo-controlled trials of donepezil in the treatment of mild-moderate Alzheimer's disease and these report significant benefits for a proportion of patients. Little is known about the use of donepezil in routine clinical practice. The aims of this study were to examine the use of donepezil in routine clinical practice and to identify some of the practical and resource implications associated with treatment. A number of areas were examined against published guidelines including assessment, diagnosis, initiation of treatment, monitoring and discontinuation of treatment. This was a retrospective case note study involving patients with mild - moderate Alzheimer's disease over a one-year period. One hundred and seventeen patients were commenced on donepezil and 93 successfully completed three months of treatment. Of these, 47% demonstrated an improvement in cognition, activities of daily living or carer observation (or a combination). Compliance with accepted guidelines with respect to assessment, diagnosis and monitoring requires a standardised approach that has both clinical and resource implications.

Activities of Daily Living↗

A prospective study examining the association between the symptoms of anxiety and depression and severity of urinary incontinence.

OBJECTIVE: To investigate the association of the presence or absence of the symptoms of anxiety and depression compared with the 48 h pad test as an objective measure of incontinence. DESIGN: Prospective study. SETTING: Urodynamics clinic in a large teaching hospital. SUBJECTS: All patients with urinary incontinence attending for urodynamic assessment from 23.4.96 to 29.10.96. INTERVENTIONS: 48 h pad test, Hospital Anxiety and Depression scale (HAD scale). MAIN OUTCOME MEASURES: Urodynamic diagnosis of cause of incontinence. Urinary loss over 48 h as measured by weight change in pads. Presence of symptoms of anxiety or depression as defined by HAD scale score of 8 or more. RESULTS: Urodynamic investigation was performed for incontinence on 133 patients. Of these 127 (95.4%) completed the HAD scale questionnaire. Of the 43 patients (32.2%) who returned the pads 18 (41.8%) patients were found to have symptoms of anxiety and six patients (13.9%) had symptoms of depression. Patients with symptoms of anxiety had lower mean measured urinary loss over a 48 h period compared to women with no symptoms of anxiety (median loss 44.2 ml range 6.8-622.4 versus 97.1 ml range 8.2-4384.4 ml) (P=0.05). There was no significant association between symptoms of depression and pad test results. CONCLUSIONS: Patients presenting with incontinence who have symptoms of anxiety are on average less incontinent compared to than those without symptoms of anxiety. It suggests that anxious patients present with a lesser degree of incontinence than nonanxious patients.

Anxiety↗

Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis.

The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, whose physiological functions include tissue remodelling and embryogenesis. The importance of this group of proteins in the processes of tumour invasion and metastasis is now widely acknowledged, and has led to the search for MMP inhibitors for use as anticancer treatments in a clinical setting. This review aims to bring the reader up-to-date with current research relating to MMPs, with particular emphasis on emerging mechanisms of regulation of these enzymes, and their interaction with cell adhesion molecules. The therapeutic inhibition of MMPs will also be discussed.

Cadherins↗

Laser capture microscopy.

Human tissues are composed of complex admixtures of different cell types and their biologically meaningful analysis necessitates the procurement of pure samples of the cells of interest. Many approaches have been used in attempts to overcome this difficulty, including a variety of microdissection methods. This review concerns a recent advance in microdissection techniques, namely laser capture microdissection (LCM). The principle underlying this technique is outlined, and practical issues pertaining to LCM are considered. In addition, the literature relating to LCM is reviewed, with examples of research applications of this technique being outlined.

Cell Separation↗

Expression of cell cycle control proteins in primary colorectal tumors does not always predict expression in lymph node metastases.

Analysis of tumor markers focuses on expression in primary tumors with the assumption that this is representative of metastatic tumor, against which treatment is targeted. Few studies have compared the expression of such markers in primary and secondary tumors. In this study, several key genes involved in cell cycle regulation were investigated in colorectal tumors and corresponding lymph node metastases. The cell cycle regulators p53, cyclin D1, p21, p27, retinoblastoma protein (Rb), and proliferating cell nuclear antigen (PCNA) were examined in a series of 42 paired samples of primary colorectal and secondary lymph node tumors by immunohistochemistry. Expression of p53, p27, and Rb was similar in virtually all paired samples (p53, 38 of 42; p27, 39 of 42; Rb, 40 of 42), indicating that the pattern of these proteins in colorectal tumors may be used to predict that in lymph node tumors. It also suggests a lack of direct involvement in the metastatic process. A lower concordance for p21 and cyclin D1 staining was observed between primary and secondary tumors (p21, 19 of 42; cyclin D1, 22 of 42). p21 expression was more often observed in primary colorectal cancers, whereas cyclin D1 expression was more frequently seen in lymph node metastases, in keeping with the contrasting roles of these proteins as a cell cycle inhibitor (p21) and activator (cyclin D1). The PCNA-labeling index was found to vary considerably in a number of cases, thus limiting the ability to predict expression of this protein in lymph node metastases from the primary tumor. In addition, PCNA-labeling indices between paired samples were neither consistently higher nor lower, suggesting that the proliferative capacity of tumor cells is not directly related to their ability to metastasize.

Adult↗

Matrix metalloproteinases in tumour invasion and metastasis.

The matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes, which are involved in the degradation of many different components of the extracellular matrix. The MMPs have been classified into different groups including collagenases, gelatinases, stromelysins, and others, particularly membrane-type MMPs, based mainly on the in vitro substrate specificity of individual MMPs. There is increasing evidence to indicate that individual MMPs have important roles in tumour invasion and metastasis. However, the current concept of the role of MMPs in tumour invasion is that they not only have a direct role in tumour invasion by facilitating extracellular matrix degradation, but as a consequence they also have an important role in maintaining the tumour micro-environment and thus promoting tumour growth. Inhibiting the action of MMPs represents a new therapeutic approach for the treatment of individual types of cancer and several broad-spectrum, low-molecular-weight MMP inhibitors are currently being assessed for clinical use. This review examines the role of MMPs in tumour invasion and metastasis, with an emphasis on studies of clinical relevance.

Humans↗

Psychopathology 8 1/2 years post parasuicide.

There are few long-term follow-up studies of parasuicides incorporating face-to-face interviews. To date no study has evaluated the prevalence of psychiatric morbidity at long-term follow-up of parasuicides using diagnostic rating scales, nor has any study examined parental bonding issues in this population. We attempted a prospective follow-up of 85 parasuicide cases an average of 8 1/2 years later. Psychiatric morbidity, social functioning, and recollections of the parenting style of their parents were assessed using the Clinical Interview Schedule, the Social Maladjustment Scale, and the Parental Bonding Instrument, respectively. Thirty-nine persons in total were interviewed, 19 of whom were well and 20 of whom had psychiatric morbidity. Five and died during the follow-up period, 3 by suicide. Migration, refusals, and untraceability were common. Parasuicide was associated with parental overprotection during childhood. Long-term outcome is poor, especially among those who engaged in repeated parasuicides.

Adolescent↗

Selecting an antidepressant for use in a patient with epilepsy. Safety considerations.

Depression is a common and disabling condition and is especially disabling for patients who also have epilepsy. Antidepressants, particularly the tricyclic antidepressants are well known to be associated with seizure activity, but this is a very neglected area of research. Most of the data on the proconvulsive effects of antidepressants come from either work in animal models or from research into the effects of antidepressants in overdose. Both of these situations may tell us little about the behaviour of antidepressants in patients with epilepsy. The selective serotonin [5-hydroxytryptamine; 5-HT] reuptake inhibitors have a low seizure propensity, are well tolerated in overdose and have a favourable adverse effect profile, making them suitable as first line treatments for depression in patients with epilepsy. Other antidepressants, e.g. trazodone, moclobemide, mirtazepine, are also likely to have minimal proconvulsive effects, but adverse effects, interactions with other drugs, especially anticonvulsants, or the lack of clinical data may make their use less attractive. Although this review has focused on these clinically important issues it is clear that considerably more research needs to be undertaken on the seizure propensity and clinical efficacy of antidepressants in patients with epilepsy.

Antidepressive Agents↗

Distribution of putative primordial germ cells in equine embryos.

Eighteen equine embryos, 3 each on Days 20, 22, 24, 26, 28 and 30 post ovulation, were collected transcervically by uterine lavage, fixed in 4% paraformaldehyde and embedded in paraffin wax. Ten micron serial sections were stained to determine alkaline phosphatase (AP) activity in the cells. Positive cells were counted and their approximate location determined. The cells were approximately 8 microm in diameter and the entire cell, except the nucleus, stained strongly with many small round areas of intense staining in the cytoplasm. The cells varied from round to elongated in shape and pseudopodia were often present. Thus, they were similar in shape and staining pattern to primordial germ cells described in other species. A total of 2 AP-positive cells were found in the 3 Day 20 embryos and the mean number of AP-positive cells changed (P<0.05) over the succeeding days as follows; Day 20 = 1; Day 22 = 251; Day 24 = 1484; Day 26 = 2385; Day 28 = 3267; Day 30 = 2424. AP-positive cells present in the liver were not included in the calculations. In the Day 22 embryos, 10% of the putative primordial germ cells were found within the vascular system, including the heart chambers, and only 4% were found along the genital ridge. The percentage of cells found in the vascular system decreased from 10% on Day 22 to 1% on Day 30, although not significantly. The percentage of cells found along the genital ridge changed (P<0.05) over gestational age as follows; Day 22 = 4%; Day 24 = 10%; Day 26 = 28%; Day 28 = 28%; Day 30 = 16%. Once the putative primordial germ cells reached the developing gonads they were no longer AP-positive and nor was the gonadal stroma. The rest of the cells were distributed along the dorsal mesentery (range, 14-24%), near the dorsal aorta (16-29%), in the mesonephros (1-3%) and in other areas of the embryo (27-44%). Large numbers were in the cranial portion of the embryo. Although it is likely that the population of AP-positive cells counted included the primordial germ cells, other cells, such as haematopoietic precursor cells, could not be ruled out. The AP reactivity, the appearance of the cells and their migratory pattern through the dorsal mesentery to the gonadal ridge were consistent with descriptions of primordial germ cells in other species. Their distribution throughout the embryo, especially its cranial aspect and their location within, or in close proximity to, blood vessels suggested that the equine embryo is unusual among mammals in that some of its primordial germ cells migrate through the blood.

Alkaline Phosphatase↗