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Biomedical subjects

A Morgan

Publications and source records attributed to A Morgan.

At least 55 records · Page 3Linked to original sources
PubMed2000

Disconnecting hippocampal projections to the anterior thalamus produces deficits on tests of spatial memory in rats.

A disconnection procedure was used to test whether projections from the hippocampus to the anterior thalamic nuclei (AT), via the fimbria-fornix (FX), form functional components of a spatial memory system. The behavioural effects of combined unilateral lesions in the AT and FX were compared when they were either in contralateral hemispheres (AT-FX Contra) or the same hemisphere (AT-FX Ipsi). Other groups received bilateral FX lesions and Sham surgeries. Expt 1 demonstrated that none of these lesions affected performance of an object recognition task, while performance of an object location task, which tests the subjects' preference for an object that has changed location, was impaired in the AT-FX Contra and FX groups. In a T-maze alternation task, however, the FX group was severely impaired while both the AT-FX Ipsi and AT-FX Contra lesion groups showed only a mild impairment. In order to test whether spared crossed projections might support spatial performance in the AT-FX Contra group we then examined the effects of a combined AT-FX Contra lesion coupled with transection of the hippocampal commissure. This combination of lesions produced a severe disruption in spatial memory performance in the water maze, radial arm maze and T-maze, which was significantly greater than that produced by ipsilateral and contralateral AT-FX lesions alone. These results support the notion that disconnection of the AT from their hippocampal inputs produces impairments on a range of spatial memory tasks, but indicate that there are an array of different routes that can subserve this function.

Animals↗
PubMed2000

Individual and group psychotherapy with infertile couples.

After reviewing some of the relevant literature, the writers proceed to describe a new development in psychotherapy for couples presenting with relatively unexplained infertility. Several couples who had failed to achieve conception (despite the use of assisted reproductive techniques and personal psychotherapy) were brought together into a supportive-expressive group led by the writers, an experienced analytic cotherapy couple. An interesting outcome is described, and mention made of current plans for a future research project.

Adult↗
PubMed2000

A screen for dominant negative mutants of SEC18 reveals a role for the AAA protein consensus sequence in ATP hydrolysis.

An evolutionarily ancient mechanism is used for intracellular membrane fusion events ranging from endoplasmic reticulum-Golgi traffic in yeast to synaptic vesicle exocytosis in the human brain. At the heart of this mechanism is the core complex of N-ethylmaleimide-sensitive fusion protein (NSF), soluble NSF attachment proteins (SNAPs), and SNAP receptors (SNAREs). Although these proteins are accepted as key players in vesicular traffic, their molecular mechanisms of action remain unclear. To illuminate important structure-function relationships in NSF, a screen for dominant negative mutants of yeast NSF (Sec18p) was undertaken. This involved random mutagenesis of a GAL1-regulated SEC18 yeast expression plasmid. Several dominant negative alleles were identified on the basis of galactose-inducible growth arrest, of which one, sec18-109, was characterized in detail. The sec18-109 phenotype (abnormal membrane trafficking through the biosynthetic pathway, accumulation of a membranous tubular network, growth suppression, increased cell density) is due to a single A-G substitution in SEC18 resulting in a missense mutation in Sec18p (Thr(394)-->Pro). Thr(394) is conserved in most AAA proteins and indeed forms part of the minimal AAA consensus sequence that serves as a signature of this large protein family. Analysis of recombinant Sec18-109p indicates that the mutation does not prevent hexamerization or interaction with yeast alpha-SNAP (Sec17p), but instead results in undetectable ATPase activity that cannot be stimulated by Sec17p. This suggests a role for the AAA protein consensus sequence in regulating ATP hydrolysis. Furthermore, this approach of screening for dominant negative mutants in yeast can be applied to other conserved proteins so as to highlight important functional domains in their mammalian counterparts.

Adenosine Triphosphatases↗
PubMed2000

Quantifying patient preferences for out-of-hours primary care.

OBJECTIVE: To quantify public preferences for different attributes of out-of-hours primary medical care. METHODS: This study applies a technique called conjoint analysis. A focus group was convened to identify the most important attributes for inclusion in the study, followed by a postal questionnaire asking people to choose between hypothetical services containing different mixes of these attributes. Multi-variate regression analysis estimated the relative importance of different attributes to respondents. The respondents were 436 adults who were among respondents to an earlier postal survey of 25,090 randomly selected Sheffield residents. RESULTS: The doctor's manner (whether the doctor takes time to listen), the type of consultation (whether the patient receives a home visit, telephone advice, sees an accident and emergency doctor or attends a primary care treatment centre) and waiting time for consultation best predicted the public's preferences for out-of-hours care. Another three attributes--ease of access; seeing a familiar doctor; and the doctor's shift arrangements--were not statistically significant. CONCLUSIONS: By asking people to make simple choices between hypothetical services, it is possible to quantify their strength of preference for different aspects of a service. This has important implications for the planning of services. Specifically, for out-of-hours services, more consideration should be given to the doctor's manner and waiting times rather than familiarity of doctor.

Data Interpretation, Statistical↗
PubMed2000

Palliative care nursing in rural Western Australia.

This article presents the findings of a study of rural palliative care nurses in Western Australia. The number of rural centres in Western Australia offering palliative care services is increasing; however, at present there is little empirical data available about the roles of the nurses involved. This study was undertaken to begin to correct this deficit. The study examined basic social processes associated with the role of rural palliative care nurses, and identifies issues that affect the nurses' professional practice. A modified grounded theory approach was used to form a conceptual framework that describes rural palliative care nursing. Theoretical sampling techniques were used to identify the six palliative care nurses working in rural Western Australia who participated in the study. Data were generated using in-depth interview and participant observation techniques. Constant comparative analysis of the data was employed to allow concepts to emerge from the data. The central theme that developed is the all-consuming nature of the rural palliative care nurse's role. Three subthemes relating to multiple roles, expectations of nurses, and coping strategies are also discussed. This research explored issues that rural palliative care nurses feel are relevant to their professional practice, and it describes the basic social processes inherent in the rural palliative care nurse's role. Recommendations for nursing research, education, administration and clinical practice are presented.

Adaptation, Psychological↗
PubMed2000

Costs and benefits of community postnatal support workers: a randomised controlled trial.

OBJECTIVES: This study aimed to measure the effect and the total cost per woman of providing postnatal support at home, based on a Dutch model. The research hypothesis was furnished by some existing evidence that postnatal support could reduce the risk of postnatal depression and encourage breastfeeding. DESIGN: The randomised controlled trial aimed to measure differences in health status in a group of women who were offered postnatal support from a community midwifery support worker (SW) compared with a control group of women who were not offered this support. Women were followed-up by postal questionnaire at 6 weeks and 6 months postnatally. SETTING AND SUBJECTS: All women who delivered a baby at the recruiting hospital were eligible to take part in the trial if they lived within the study area, were aged 17 years or over, and could understand English. INTERVENTION: The intervention consisted of the SW offering practical and emotional support and to help women rest and recover after childbirth. The SW offered ten visits in the first 28 days postnatally, for up to 3 hours per day. The SW's activities included housework, talking with the mother, and care for the baby or other siblings. The service was provided in addition to routine visits by the community midwife. MAIN OUTCOME MEASURES: The primary outcome was the general health perception domain of the Short Form-36 at 6 weeks. Secondary outcomes were mean Edinburgh Postnatal Depression Scale (EPDS), Duke Functional Social Support (DUFSS) scores and breastfeeding rates. RESULTS: The 623 randomised women were well-matched by group with a good response to follow-up. At 6 weeks there was no evidence of a significant difference between the two groups for the primary outcome. There was a non-significant trend for the control group to have better mean DUFSS and EPDS scores at 6 weeks. Breastfeeding rates were not significantly different at follow-up. At 6 months, both groups had similar health status. Satisfaction with the service was higher than for all other services received. The incremental cost of introducing the service comprised setting up and running the service. There were no differences between the groups in other resource use (general practitioner contacts, hospital services, prescriptions or medicines bought for mothers and babies) to 6-month follow-up. The total mean NHS cost to 6-month follow-up for the intervention group was pound180 per woman greater than for the control group (confidence interval, pound79.60, pound272.40). CONCLUSIONS: Although women valued the service, there was no evidence of any health benefit at the 6-week or 6-month follow-up, no difference in use of NHS services, and the additional cost of the service provision would be around pound 180 per woman.

Adolescent↗
PubMed1999

nSec-1 (munc-18) interacts with both primed and unprimed syntaxin 1A and associates in a dimeric complex on adrenal chromaffin granules.

The target-SNARE syntaxin 1A is an essential component of the core machinery required for regulated exocytosis (where SNARE is the soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor). Syntaxin 1A interacts with a variety of other proteins, two of which, N-ethylmaleimide-sensitive fusion protein (NSF) and alpha-soluble NSF attachment protein (alpha-SNAP) have been suggested to impart a conformational rearrangement on this protein during a reaction referred to as priming. We have studied the effect of the primed state on the binding properties of syntaxin 1A and we have confirmed that primed syntaxin 1A no longer associated with alpha-SNAP or its cognate vesicle-SNARE, vesicle-associated membrane protein (VAMP). Under such conditions, however, it retained the ability to bind to nSec-1. It has been demonstrated that nSec-1, a regulatory protein also involved in neuronal exocytosis, binds syntaxin 1A with high affinity in vitro, although evidence for this physical interaction occurring in vivo has proven elusive. We analysed the subcellular distribution of these two proteins in fractions from bovine adrenal medulla and detected syntaxin 1A and nSec-1 in both plasma membrane and chromaffin-granule fractions. Using a cross-linking approach with chromaffin-granule membranes we detected a putative dimeric complex composed of approx. 54% total granule membrane nSec-1 and approx. 30% total syntaxin 1A. The results of this study therefore suggest the possibility of nSec-1 interactions with primed syntaxin 1A and demonstrate a potentially significant interaction of syntaxin 1A and nSec-1 on the membranes of chromaffin granules.

Adrenal Medulla↗
PubMed1999

The isoprostane, 8-epi-PGF2 alpha, is accumulated in coronary arteries isolated from patients with coronary heart disease.

OBJECTIVE: In the present study we wanted to know whether 8-epi-PGF2 alpha, which belongs to the class of isoprostanes formed by free radical-mediated peroxidation of arachidonic acid and arachidonyl-containing phospholipids, is enriched in isolated coronary arteries of patients suffering from coronary heart disease (CHD, n = 23) who received allograft heart transplants as compared to vessels derived from patients with dilative cardiomyopathy (CMP, n = 19) or from healthy heart donors (controls, n = 6). METHODS: Sections from the isolated coronary arteries were analysed by semiquantitative immunohistochemistry by determining the area and intensity of positive reaction for 8-epi-PGF2 alpha in the vascular intima and media. In addition, the 8-epi-PGF2 alpha content was determined using a specific immunoassay after extraction and purification. RESULTS: The immunohistochemical results indicated that 8-epi-PGF2 alpha is significantly enriched in arteries from patients suffering from CHD as compared to CMP (P < 0.0001). In controls, significantly less immunostaining was observed. Furthermore, a significant positive correlation between semiquantitative immunohistochemistry and radioimmunological determination was observed too. CONCLUSIONS: From our findings we conclude that 8-epi-PGF2 alpha is especially accumulated in coronary arteries from CHD patients and therefore is likely to be involved in atherogenesis.

Analysis of Variance↗
PubMed1999

Biochemical analysis of the Saccharomyces cerevisiae SEC18 gene product: implications for the molecular mechanism of membrane fusion.

The SEC18 gene product is 48% identical to mammalian NSF (N-ethylmaleimide-sensitive fusion protein), and both proteins encode cytoplasmic ATPases which are essential for membrane traffic in yeast and mammalian cells, respectively. A wealth of biochemical analysis has led to the description of a model for the action of NSF; through its interaction with SNAPs (soluble NSF attachment proteins), NSF can associate with SNAP receptors (SNAREs) on intracellular membranes, forming 20S complexes. SNAPs then stimulate the intrinsic ATPase activity of NSF, leading to the disassembly of the 20S complex, which is essential for subsequent membrane fusion. Although this model is based almost entirely on in vitro studies of the original clones of NSF and alpha-SNAP, it is nevertheless widely assumed that this mechanism of membrane fusion is conserved in all eukaryotic cells. If so, the crucial biochemical properties of NSF and SNAPs should be shared by their yeast homologues, Sec18p and Sec17p. Using purified recombinant proteins, we report here that Sec18p can specifically interact not only with Sec17p but also with its mammalian homologue, alpha-SNAP. This interaction leads to a stimulation of Sec18p D1 domain ATPase activity, with kinetics similar to those of alpha-SNAP stimulation of NSF, although differences in temperature and N-ethylmaleimide sensitivity were observed between NSF and Sec18p. Furthermore, Sec18p can interact with synaptic SNARE proteins and can synergize with alpha-SNAP to stimulate regulated exocytosis in mammalian cells. We conclude that the mechanistic properties of NSF and SNAPs are shared by Sec18p and Sec17p, thus demonstrating that the biochemistry of membrane fusion is conserved from yeast to mammals.

Adenosine Triphosphatases↗
PubMed1999

No association between D2 dopamine receptor (DRD2) "A" system alleles, or DRD2 haplotypes, and posttraumatic stress disorder.

BACKGROUND: Association studies between marker alleles at the D2 dopamine receptor gene (DRD2) and various psychiatric illnesses have produced conflicting results. Reports of allelic associations were originally made with alcoholism, but were then extended to other psychiatric disorders, including posttraumatic stress disorder (PTSD). METHODS: We studied allele frequency of the DRD2 TaqI "A," "B," and "D" system markers in 52 European-American subjects with diagnoses of PTSD (based on structured interviews). RESULTS: Frequency of the A1 allele in this sample was .15, not significantly different from the .19 allele frequency seen in 87 control subjects. We were thus unable to replicate the previous reports of allelic association between the DRD2 TaqI "A1" allele and PTSD. There were also no significant differences in allele frequency for the "B" or "D" systems. We then computed three marker (TaqI "A," "B," and "D" system) haplotypes for the sample; DRD2 haplotype frequencies also did not differ between control subjects and subjects with PTSD. CONCLUSIONS: We conclude that DRD2 alleles are not associated with PTSD in this sample, and that genetic variation at the DRD2 locus is not likely to be an important contributor to risk for this disorder.

Adult↗
PubMed1999

Initial experience in a community hospital with sentinel lymph node mapping and biopsy for evaluation of axillary lymph node status in palpable invasive breast cancer.

BACKGROUND AND OBJECTIVES: To determine the sentinel node detection rate and the accuracy with which the sentinel node histology reflects that of the axilla in a series of patients with palpable invasive breast cancer. METHODS: Forty-four patients with clinically node-negative palpable invasive T1 or T2 breast tumors underwent sentinel node biopsy using isosulfan blue dye, followed immediately by either local excision of the primary lesion with standard axillary lymph node dissection or modified radical mastectomy. All surgeries were performed at Northwest Hospital, Seattle, Washington, between January 1996 and October 1997. RESULTS: The sentinel node was successfully identified in 73% of the patients (32/44). The frequency of sentinel node detection was greater for tumors in the outer quadrants than the inner quadrants (z-test, P < 0.001). Of the 32 patients in whom a sentinel node was identified, 10 (31%) had histologically positive sentinel nodes: 5 (16%) by frozen section, 2 additional patients (6%) after permanent hematoxalin-eosin (H&E) stained sections, and the remaining 3 (9%) after immunohistochemical stains for cytokeratins when the FS and permanent H&E-stained sections were benign. Twenty patients had benign axilla. The sentinel node was falsely negative in 2 patients, yielding an accuracy of 93.8%, sensitivity of 83.3%, and negative predictive value of 91%. CONCLUSIONS: Lymphatic mapping is technically feasible for patients with small (T1 or T2) palpable invasive breast tumors. The sentinel node can be reliably identified in the majority of these patients, and its histology reflects that of the axilla with a high degree of accuracy. Immunohistochemical stains and permanent H&E-stained sections of the sentinel node increased the test's ability to correctly identify axillary metastases. Improving this sensitivity remains a primary goal, however, if benign sentinel node histology is to be used as a criterion to preclude axillary dissection.

Adult↗
PubMed1999

Comparable changes in synaptic dopamine induced by methylphenidate and by cocaine in the baboon brain.

Though the blockade of dopamine transporters (DAT) is associated with cocaine's and methylphenidate's reinforcing effects, it is the stimulation of dopamine (DA) receptors, achieved by increases in synaptic DA, that enables these effects to occur. Positron emission tomography (PET) and [11C]raclopride were used to assess the levels of occupancy of DA D2 receptors by dopamine achieved by doses of cocaine or methylphenidate previously documented to block over 70% of DAT. Studies were performed in five baboons using a paired scan protocol designed to measure DA D2 receptor availability (Bmax/Kd) at baseline conditions and after intravenous administration of either cocaine or methylphenidate. Cocaine (1-2 mg/kg) or methylphenidate (0.5 mg/kg) administered 5 min prior to [11C]raclopride decreased Bmax/Kd by 29+/-3% and 32 + 4%, respectively. Smaller reductions in Bmax/Kd (13% for cocaine given 30 min before [11C]raclopride and 25+/-10% for methylphenidate given 40 min before [11C]raclopride) were seen with longer periods between drug and radioligand. These observations are consistent with the slower striatal clearance kinetics of [11C]methylphenidate than [1C]cocaine observed in previous PET experiments and with the approximately twofold higher potency of methylphenidate than cocaine in in vitro experiments. Though the elevation of synaptic DA induced by >70% occupancy of DAT by these drugs lead to a modest increase in occupancy of D2 receptors (25-30%), further studies are required to assess if this is an underestimation because of differences in D2 receptor binding kinetics between raclopride and DA.

Animals↗
PubMed1999

Clinical picture of women with early stage ovarian cancer.

OBJECTIVE: The objective of this study was to review the clinical picture of women with early stage ovarian cancer, to examine the difference between women with borderline ovarian tumors (BLOT) and those with ovarian cancer (OC), and to estimate the average time interval between the onset of symptoms and diagnosis. METHODS: A retrospective review of all women with surgical stage I and II OC or BLOT was performed and the following information abstracted: age, parity, family history of cancer, personal history of previous malignancies, symptoms, signs, date of start of symptoms, imaging studies, CA-125 values, date of diagnosis at surgery, tumor stage, histology, grade, date of last follow-up, and condition at last follow-up. Comparison between patients with BLOT and OC was performed using chi(2) and two-sample t tests. RESULTS: Our search identified 72 women with surgical stage I and II BLOT (n = 22) or OC (n = 50). Seventy-eight percent of the patients had presenting symptoms, the most common of which were abdominal or pelvic pain (34. 7%), bloatedness (31.9%), and vaginal bleeding (19.4%). Symptoms were similar among women with BLOT and those with OC, with a higher proportion of BLOT patients reporting no symptoms (31.8% versus 18. 0%, respectively). Abdominal and/or pelvic masses were palpable in 72.2% of the patients and ascites was present in 12.5%. Ovarian masses were most commonly complex in appearance and CA-125 was elevated in 52.2% of the patients in whom CA-125 values were known. The average time interval between onset of symptoms and diagnosis was 4.6 months (range 0.1-24.4 months). Women with BLOT had a significantly longer average time interval than women with OC (8.0 +/- 7.7 versus 3.4 +/- 3.7 months, respectively, P = 0.03). CONCLUSIONS: The majority of women with early stage ovarian cancer have nonspecific symptoms. The array of symptoms is similar between women with BLOT and those with OC. However, women with BLOT tend to have a longer time interval from onset of symptoms to diagnosis.

Adolescent↗
PubMed1999

Protein phosphorylation and the regulation of synaptic membrane traffic.

It is well established that protein phosphorylation has an important role in synaptic plasticity. This is achieved, in part, via the presynaptic modulation of neurotransmitter release by protein kinases and protein phosphatases. In recent years, the increase in information available about proteins that are involved in synaptic exocytosis and endocytosis has been exploited in order to study the effects of protein phosphorylation on synaptic-vesicle cycling at the molecular level. The best-characterized protein in this respect is synapsin, whose function in the release of synaptic vesicles from the reserve pool is regulated by phosphorylation. More recently, it has emerged that proteins that function at other stages of the synaptic-vesicle cycle, which include priming of vesicles for docking-fusion and endocytic recycling, are also controlled by phosphorylation. Furthermore, recent work suggests that this regulation of membrane traffic by phosphorylation also occurs postsynaptically, where it contributes to synaptic plasticity.

Animals↗
PubMed1999

Does pretraining spare the spatial deficit associated with anterior thalamic damage in rats?

Rats that had been pretrained on 2 tests of allocentric memory (water maze and T maze) received bilateral cytotoxic lesions in the anterior thalamic nuclei (ATN) or transection of the fimbria-fornix (FF). After surgery, both groups of rats were impaired on both tasks, although the preoperative training resulted in a rapid initial reacquisition of the water maze task. Those rats with lesions largely restricted to the ATN were impaired at a level comparable to that produced by FF lesions. This finding is consistent with a close functional relationship between the hippocampus and the ATN, necessary for the acquisition and on-line processing of allocentric spatial information but not for the maintenance/retrieval of procedural information. The rats with more extensive thalamic lesions were more impaired in both tasks and did show a loss of procedural information.

Animals↗
PubMed1998

Stimulation of NSF ATPase activity during t-SNARE priming.

N-Ethylmaleimide-sensitive factor (NSF) plays a key role in vesicular traffic by disassembling and priming SNARE proteins for their function in docking and fusion. We demonstrate that the ATPase activity of NSF is activated by alpha-soluble NSF attachment protein (alpha-SNAP) in a complex with syntaxin 1A. In addition, we show that a construct consisting of the H3 domain of syntaxin IA (GST-synt(195-263), which does not support NSF disassembly in the presence of MgATP gave a larger stimulation. NSF ATPase activation was specific and did not occur using mutant alpha-SNAPs unable to bind GST-synt or with mutated C-termini. We suggest that activation of NSF ATPase activity in the SNARE complex may be essential to allow SNARE priming.

Adenosine Triphosphate↗