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K Murphy

Publications and source records attributed to K Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1999

Cortical and subcortical control of tongue movement in humans: a functional neuroimaging study using fMRI.

We have used voluntary tongue contraction to test whether we can image activation of the hypoglossal nuclei within the human brain stem by using functional magnetic resonance imaging (fMRI). Functional images of the whole brain were acquired in eight subjects by using T2-weighted echo planar imaging (blood oxygen level development) every 6.2 s. Sequences of images were acquired during 12 periods of 31-s "isometric" rhythmic tongue contraction alternated with 12 periods of 31-s tongue relaxation. Noise arising from cardiac- and respiratory-related movement was removed either by filtration (high pass; cutoff 120 s) or by inclusion in the statistical analysis as confounding effects of no interest. For the group, tongue contraction was associated with significant signal increases (P < 0.05 corrected for multiple comparisons) in the sensorimotor cortex, supplementary motor area, operculum, insula, thalamus, and cerebellum. For the group and for six of eight individuals, significant signal increases were also seen within the medulla (P < 0.001, predefined region of interest with no correction for multiple comparisons); this signal is most likely to reflect neuronal activation associated with the hypoglossal motor nuclei. The data demonstrate that fMRI can be used to detect, simultaneously, the cerebral and brain stem control of tongue movement.

Adult↗
PubMed1999

Modulation of the corticospinal control of ventilation by changes in reflex respiratory drive.

We have determined whether changes in PCO(2) above and below eucapnia modulate the precision of the voluntary control of breathing. Twelve trained subjects performed a compensatory tracking task in which they had to maintain the position of a cursor (perturbed by a variable triangular forcing function) on a fixed target by breathing in and out of a spirometer (ventilatory tracking; at 10 l/min). Before each task, subjects hyperventilated for 5 min, and the end-tidal PCO(2) (PET(CO(2))) was controlled; tracking was then performed separately at hypocapnia, eucapnia, and hypercapnia (PET(CO(2)) approximately 25, 37, and 43 Torr, respectively). Ventilatory tracking error was unchanged during hypocapnia (P > 0.05) but was significantly worse during hypercapnia (P < 0.003), compared with eucapnia; arm tracking error, performed as a control, was not significantly affected by PET(CO(2)) (P > 0. 05). In conclusion, ventilatory tracking performance is unaffected by the eucapnic PCO(2). From this, we suggest that resting breathing in awake humans may be independent of chemical drives and of the prevailing PCO(2).

Adult↗
PubMed1999

LIM domain-containing protein trip6 can act as a coactivator for the v-Rel transcription factor.

The retroviral oncoprotein v-Rel is a transcriptional activator in the Rel/NF-kappaB family of eukaryotic transcription factors. v-Rel malignantly transforms a variety of cell types in vitro and in vivo, and its transforming activity is dependent on the ability of v-Rel to bind to DNA and activate transcription. In this report, we used the yeast two-hybrid assay to identify proteins that interact with C-terminal sequences of v-Rel that are needed for transcriptional activation and transformation. One protein, Trip6, that we identified in this screen was previously identified as a thyroid hormone receptor-interacting protein. Trip6 is a member of a subfamily of LIM domain-containing proteins that are thought to transport intracellular signals from the cell surface to the nucleus. By several criteria, we show that sequences from Trip6, which include the LIM domains, behave as a coactivator for transcriptional activation by v-Rel. That is, a GAL4-Trip6 fusion protein can activate transcription in yeast and chicken cells, Trip6 can enable C-terminal sequences of v-Rel to activate transcription in yeast, and Trip6 can enhance activation by v-Rel from a kappaB site reporter plasmid in yeast. Although full-length Trip6 localizes to adhesion plaques, deletion of N-terminal sequences allows human Trip6 to enter the nucleus of chicken cells. Lastly, Northern blotting shows that Trip6 mRNA is expressed in many human tissues. Coexpression of Trip6 does not affect the transforming activity of v-Rel. Taken together, our results indicate that Trip6 may be a protein that is important for the ability of v-Rel to activate transcription and transform cells, and may represent a potential target for blocking Rel-mediated oncogenesis and transcriptional activation.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1999

Psychosocial functioning in chronic epilepsy: relation to hippocampal volume and histopathological findings.

MRI volumetric measurements of the ipsi- and contralateral hippocampal volume (HV) were performed in a group of 37 patients with lesional and non-lesional temporal (TLE), and extratemporal lobe (ETLE) lobe epilepsy. Twenty-six patients underwent surgery and the resected tissues subjected to histopathological examination. Psychosocial scores were calculated on the basis of employment, partnership/family status and presence of a positive psychiatric history. Poorest values were obtained for the group with right lesional and non-lesional TLE (RTLE, p < 0.001). In this group, significant positive correlations between psychosocial functioning and the left hippocampal volume or age of onset were observed. We found that the left hippocampal volume in RTLE was smaller with increasing epilepsy duration. We conclude that patients with RTLE represent a particular group with regard to the structural and psychosocial consequences of chronic epilepsy. With regard to histopathological analysis, no particular type of lesion was identified as the major determinant of the results described above.

Adult↗
PubMed1998

Four-year follow-up of Palmaz-Schatz stent revascularization as treatment for atherosclerotic renal artery stenosis.

BACKGROUND: Stent revascularization is perceived as superior to balloon angioplasty and surgical revascularization, but the paucity of stent publications precludes even historical comparison with surgical data. METHODS AND RESULTS: Palmaz-Schatz stent revascularization of renal artery stenosis was successfully performed on 163 consecutive patients for poorly controlled hypertension or preservation of renal function. Of these, 145 were eligible for > or =6-month clinical follow-up of the effect of the procedure on renal function, blood pressure control, number of antihypertensive medications, and survival. At 4 years, systolic and diastolic blood pressures significantly decreased (from 166+/-26 to 148+/-22 mm Hg and from 86+/-14 to 80+/-11 mm Hg, respectively; P<0.05), and blood pressure control was more facile in approximately half of the patients. Creatinine decreased or remained stable in approximately two thirds of the patients. The cumulative probability of survival was 74+/-4% at 3 years, with few deaths related to end-stage renal disease. Survival was good in patients with normal (92+/-4%) baseline renal function, fair (74+/-7%) in those with mildly impaired renal function, and poor (52+/-7%) in patients with elevated baseline creatinine levels (> or =2.0 mg/dL). The combination of impaired renal function and bilateral disease adversely affected survival. CONCLUSIONS: Renal artery stent revascularization in the presence of normal or mildly impaired renal function had a beneficial effect on blood pressure control and a nondeleterious effect on renal function. Survival was adversely affected by renal dysfunction despite adequate revascularization. Early diagnosis and adequate revascularization before the onset of renal dysfunction could beneficially affect blood pressure control, preserve or prevent deterioration of renal function, and improve patient survival.

Actuarial Analysis↗
PubMed1998

6-C-kine (SLC), a lymphocyte adhesion-triggering chemokine expressed by high endothelium, is an agonist for the MIP-3beta receptor CCR7.

The beta chemokine known as 6-C-kine, secondary lymphoid-tissue chemokine (SLC), TCA4, or Exodus-2 (herein referred to as 6CK/SLC) can trigger rapid integrin-dependent arrest of lymphocytes rolling under physiological shear and is highly expressed by high endothelial venules, specialized vessels involved in lymphocyte homing from the blood into lymph nodes and Peyer's patches. We show that 6CK/SLC is an agonist for the lymphocyte chemoattractant receptor, CCR7 (EBI-1, BLR-2), previously described as a receptor for the related beta chemokine MIP-3beta (ELC or Exodus-3). Moreover, 6CK/SLC and MIP-3beta attract the same major populations of circulating lymphocytes, including naive and memory T cells > B cells (but not natural killer cells); desensitization to MIP-3beta inhibits lymphocyte chemotaxis to 6CK/SLC but not to the alpha chemokine SDF-1 (stromal cell-derived factor); and 6CK/SLC competes for MIP-3beta binding to resting mouse lymphocytes. The findings suggest that the majority of circulating lymphocytes respond to 6CK/SLC and MIP-3beta in large part through their common receptor CCR7 and that these molecules may be important mediators of physiological lymphocyte recirculation in vivo.

Animals↗
PubMed1998

Does the motor cortical control of the diaphragm 'bypass' the brain stem respiratory centres in man?

In humans, cortico-motor excitation of the diaphragm may act directly on the phrenic motor nucleus via the cortico-spinal tract 'bypassing' brain stem respiratory centres (RC); alternatively, or in addition, this control may be indirect via the RC and bulbo-spinal paths. To investigate this, we stimulated the motor cortex using transcranial magnetic stimulation (TMS) in six subjects at end-expiration (diaphragm relaxed) and during voluntary inspiration. The sizes of the evoked compound action potentials in the diaphragm and also, as a control, in the thumb were no different whether TMS was delivered during normocapnia or during hypocapnia (PET(CO2) = 25 mmHg) when, presumably, the respiratory 'oscillator' was silent. In a further six subjects, TMS was performed during relaxed spontaneous breathing at three different points in the respiratory cycle. No perturbations in respiratory pattern (either tidal volume or respiratory timing) were seen. Thus we have been unable to demonstrate that the cortico-motor excitation of the diaphragm acts via the brain stem RC.

Adult↗
PubMed1998

A meta-analysis and transmission disequilibrium study of association between the dopamine D3 receptor gene and schizophrenia.

We performed a meta-analysis of over 30 case-control studies of association between schizophrenia and a bi-allelic, Bali polymorphism in exon 1 of the dopamine D3 receptor gene. We observed a significant excess of both forms of homozygote in patients (P = 0.0009, odds ratio (OR) = 1.21, 95% Confidence Interval (CI) = 1.07-1.35) in the combined sample of 5351 individuals. No significant heterogeneity was detected between samples and the effects did not appear to be the product of publishing bias. In addition we undertook an independent, family-based association study of this polymorphism in 57 parent/proband trios, taken from unrelated European multiplex families segregating schizophrenia. A transmission disequilibrium test (TDT) showed a significant excess of homozygotes in schizophrenic patients (P = 0.004, odds ratio (OR) = 2.7, 95% CI = 1.35-5.86). Although no significant allelic association was observed, a significant association was detected with the 1-1 genotype alone (P = 0.02, OR = 2.32, 95% CI = 1.13-4.99). In addition when the results of the family-based association study were included in the meta-analysis, the homozygosity effect increased in significance (P = 0.0002, OR = 1.23, 95% CI = 1.09-1.38). The results of the meta-analysis and family-based association study provide independent support for a relationship between schizophrenia and homozygosity at the Bali polymorphism of the D3 receptor gene, or between a locus in linkage disequilibrium with it.

Alleles↗
PubMed1998

A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder.

There are several lines of evidence which suggest that chromosome 4p may contain a major susceptibility locus for the functional psychoses. We previously reported a family (family 50) with cases of schizophrenia and schizoaffective disorder which gave maximum lod scores of 1.96 and 1.84 respectively with the markers D4S403 and a microsatellite near to DRD5 (DRD5-M). More recently Blackwood and co-workers described a family segregating bipolar and unipolar affective disorders which gives a maximum lod score of 4.1 with the marker D4S394, which lies 10 cM from D4S403. They obtained a combined maximum lod of 3.3 in their total sample of 12 bipolar families and found significant evidence of heterogeneity (chi 2 = 18.8, df = 2, P = 0.00008). Here we report the results of a linkage study of chromosome 4p markers in a sample of 24 multiply affected families with schizophrenia and related disorders. We obtained an overall maximum lod of 1.12 with D4S403 under both dominant and recessive modes of transmission, with no statistical support for heterogeneity within our sample. Examination of family by family data shows that only family 50 appears to show linkage at this locus. However, a discrepancy exists since our study examined families fulfilling criteria for a linkage study of schizophrenia while Blackwood et al examined families included in a genetic linkage study of bipolar disorder. This may be explained by the clinical features displayed by members of family 50, which show that all the affected members have some affective symptoms. It is therefore possible that a broad phenotype including unipolar depression, bipolar disorder, schizoaffective disorder and schizophrenia when accompanied by significant affective symptoms can result from mutations within a gene in this region. The dopamine D5 receptor gene lies within the region identified by the linkage studies and is therefore a major candidate for the putative disease gene. In family 50 we have looked for mutations of DRD5 by sequence analysis of the coding region and single stranded conformational polymorphism (SSCP) analysis of the promoter. SSCP analysis of the coding and promoter regions have also been carried out in unrelated cases of DSM-IIIR schizophrenia. Finally association studies of the (TC)n repeat in the promoter and schizophrenia, and DRD5-M and bipolar disorder were performed. These studies provided no further evidence supporting the possibility that mutations in DRD5 give rise to the linkage findings or are acting as susceptibility loci in schizophrenia or bipolar disorder.

Base Sequence↗
PubMed1998

New combination of the old drugs for elderly patients with small-cell lung cancer: a phase II study of the PAVE regimen.

PURPOSE: A regimen of cisplatin, doxorubicin, vincristine, and etoposide (PAVE) was designed for patients with small-cell lung cancer (SCLC) who were older than 65 years, with the following objectives compared with standard chemotherapy regimens: maintain efficacy, diminish toxicity, enhance compliance, and improve chemotherapy administration convenience at an acceptable cost. PATIENTS AND METHODS: The PAVE regimen consisted of cisplatin 30 mg/m2 intravenously (i.v.) day 1; doxorubicin 40 mg/m2 i.v. day 1; vincristine 1.0 mg/m2 i.v. day 1; and etoposide 100 mg/m2 i.v. day 1 and orally days 3 and 5. Cycles were repeated every 3 weeks for four cycles. Patients with limited-stage disease and selected patients with extensive-stage disease received thoracic irradiation delivered concurrently with etoposide-cisplatin (EP) at the time of the second chemotherapy cycle. RESULTS: Sixty-six eligible patients were treated, which included 25 patients with limited-stage disease and 41 patients with extensive-stage disease. Median survival was 70 weeks and 5-year survival was 25% for limited-stage disease. Median survival was 46 weeks for extensive-stage disease. Only one treatment-related death occurred and severe toxicity was infrequent. The median delivered dose-intensity was according to protocol and the mean delivered total dose was 80% of intended. CONCLUSION: The treatment outcome achieved with PAVE in a phase II study of elderly patients compared favorably with published results of standard regimens in patient populations with better prognostic factors. Because the PAVE regimen can be delivered with good compliance, has acceptable toxicity, and is associated with logistic advantages compared with standard regimens, this protocol is suitable for further investigative trials in elderly patients with SCLC.

Age Factors↗
PubMed1998

Spinal hamartomas: a distinct clinical entity.

OBJECT: Congenital spinal hamartomas are defined as tumors of well-differentiated mature elements situated in an abnormal location. In this report, the authors document the clinical and pathological features of spinal hamartomas in 10 patients. METHODS: Ten patients presented with midline dorsal malformations at birth, initially diagnosed as teratomas or myelomeningoceles. The locations of the masses were variable: two were located in the thoracic region, four at the thoracolumbar junction, two in the lumbar region, one at the lumbosacral junction, and one in the sacral region. The results of the neurological examination were normal in nine patients. All but one mass had intact skin and seven had palpable bone components. Neuroimaging studies revealed widening of the spinal canal, heterotopic bone located dorsally in some patients, and varying degrees of involvement of the intraspinal contents. During surgery, six patients were found to have involvement of the spinal cord or cauda equina. The pathological characteristics of the masses included three or more of the following: bone, cartilage, synovial membrane, urinary tract tissue, cyst wall, yellow or brown fat, and nerves. The well-differentiated cellular elements, which formed mature structures, along with the absence of primitive cellular components and neoplastic characteristics are more consistent with a diagnosis of hamartoma than teratoma. CONCLUSIONS: In this series, the authors describe a lesion that is overt on physical examination, yet can have occult spinal canal involvement. Complete neurosurgical evaluation is essential to provide appropriate treatment and prognosis.

Adipose Tissue↗
PubMed1998

Stent revascularization for atherosclerotic renal artery stenosis. 1-year clinical follow-up.

Patients who had undergone stent revascularization of renal artery stenosis for poorly controlled hypertension, preservation of renal function, or both were monitored to assess the procedure's effect upon subsequent renal function and blood pressure control. At 1-year follow-up, systolic and diastolic blood pressures had significantly decreased (166 +/- 26 to 156 +/- 25 mmHg and 86 +/- 14 to 80 +/- 13 mmHg, respectively; P < 0.05), and creatinine levels decreased or remained stable in approximately two thirds of the patients. Renal artery stent revascularization appears to have a beneficial effect upon blood pressure control and a nondeleterious effect upon renal function in the majority of patients.

Aged↗
PubMed1998

Molecular biology of septic shock.

Septic shock is a complex pathophysiologic state which often leads to multiple organ dysfunction, multiple organ failure, and death. This review summarizes current views on the molecular biology of three aspects of septic shock: recognition of bacterial invasion and induction of the cytokine response; genetic variability among humans and their predispositions toward pathologic inflammatory responses; and the signal transduction mechanisms which account for the transfer of molecular signals from cytokine receptors on the plasma membrane to cytokine-responsive genes in the nucleus. In particular, the review summarizes the pathway involved in tumor necrosis factor signaling through nuclear factor-kappaB, and elucidates the molecular signals involved in inflammatory responses and apoptosis.

Apoptosis↗
PubMed1997

Pharmacoeconomic comparison of treatments for the eradication of Helicobacter pylori.

BACKGROUND: Patients with Helicobacter pylori-induced duodenal ulcer should have their infection eradicated. The optimal choice of antibiotic therapy, however, is less clear. OBJECTIVE: To evaluate costs and outcomes of treatment with 8 antibiotic regimens with documented activity against H pylori vs maintenance therapy with histamine2-receptor antagonists (H2RA). METHODS: A meta-analysis for 119 studies enrolling 6416 patients to determine aggregate eradication rates. The complexity of each regimen was used to determine the anticipated compliance rate and actual effectiveness. A decision analytic model with Monte Carlo simulation determined annual costs and health outcomes. RESULTS: Average annual total costs of testing for H pylori infection and antibiotic treatment ranged from $223 to $410 and prevented ulcer recurrence in 70% to 86% of patients. The H2RA maintenance therapy cost $425 and prevented recurrence in 72% of patients. The lowest costs and recurrence rates were achieved by 3 regimens: standard triple therapy (a combination of bismuth subsalicylate, metronidazole, and tetracycline hydrochloride) for 14 days ($223, with 18% recurrence); a combination of clarithromycin, metronidazole, and a proton pump inhibitor for 7 days ($235, with 15% recurrence); and standard triple therapy with a proton pump inhibitor for 7 days ($236, with 14% recurrence). CONCLUSION: Treatment with any regimen resulted in lower costs compared with H2RA maintenance therapy. Three antibiotic regimens had consistently lower costs and better outcomes: standard triple therapy for 14 days, metronidazole, clarithromycin, and a proton pump inhibitor for 7 days, and standard triple therapy plus a proton pump inhibitor for 7 days.

Anti-Bacterial Agents↗
PubMed1997

Recombinant human 92-kDa type IV collagenase/gelatinase from baculovirus-infected insect cells: expression, purification, and characterization.

Human 92-kDa type IV collagenase/gelatinase (MMP9) has been expressed in insect cells and secreted into the cell medium via a baculovirus expression system. The expression level of the proenzyme from Trichoplusia ni cells was estimated to be > = 300 mg/L of cell medium. The recombinant protein was purified in a single step using heparin-affinity chromatography with an overall yield of ca. 70%. The purified zymogen could be activated in vitro using 4-aminophenylmercuric acetate to yield an active protease. Kinetic analysis of the activated recombinant enzyme demonstrates that this material is comparable to activated MMP9 from natural human sources. The recombinant enzyme provides a useful source of protein for a variety of biochemical and biophysical studies aimed at elucidating the structure and function of human MMP9.

Amino Acid Sequence↗
PubMed1997

Development of the nursing home Resident Assessment Instrument in the USA.

BACKGROUND: the nursing home Resident Assessment Instrument (RAI) includes a set of core assessment items, known as the Minimum Data Set (MDS), for assessment and care screening and more detailed Resident Assessment Protocols in 18 areas that represent common problem areas or risk factors for nursing home residents. Its primary use is clinical, to assess residents on admission to the nursing home, at least annually thereafter and on any significant change in status and to develop individualized, restorative plans of care. AIM: to describe the content and development of the RAI, including US testing for MDS item reliability and validity of the RAI, and the results of a 4-year evaluation of the effects of its clinical use. CONCLUSIONS: the evaluation found that implementation of the RAI was associated with significant improvements in a variety of measures of process quality, resident functional outcomes and reduced hospitalization. Other uses of the RAI data in the USA-including payment using resident classification systems and, with RAI-based outcome-oriented quality indicators, quality assurance activities-and the status of RAI use in other countries are also summarized.

Aged↗