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Biomedical subjects

S Spencer

Publications and source records attributed to S Spencer.

At least 55 records · Page 3Linked to original sources
PubMed1997

PSTPIP: a tyrosine phosphorylated cleavage furrow-associated protein that is a substrate for a PEST tyrosine phosphatase.

We have investigated proteins which interact with the PEST-type protein tyrosine phosphatase, PTP hematopoietic stem cell fraction (HSCF), using the yeast two-hybrid system. This resulted in the identification of proline, serine, threonine phosphatase interacting protein (PSTPIP), a novel member of the actin- associated protein family that is homologous to Schizosaccharomyces pombe CDC15p, a phosphorylated protein involved with the assembly of the actin ring in the cytokinetic cleavage furrow. The binding of PTP HSCF to PSTPIP was induced by a novel interaction between the putative coiled-coil region of PSTPIP and the COOH-terminal, proline-rich region of the phosphatase. PSTPIP is tyrosine phosphorylated both endogenously and in v-Src transfected COS cells, and cotransfection of dominant-negative PTP HSCF results in hyperphosphorylation of PSTPIP. This dominant-negative effect is dependent upon the inclusion of the COOH-terminal, proline-rich PSTPIP-binding region of the phosphatase. Confocal microscopy analysis of endogenous PSTPIP revealed colocalization with the cortical actin cytoskeleton, lamellipodia, and actin-rich cytokinetic cleavage furrow. Overexpression of PSTPIP in 3T3 cells resulted in the formation of extended filopodia, consistent with a role for this protein in actin reorganization. Finally, overexpression of mammalian PSTPIP in exponentially growing S. pombe results in a dominant-negative inhibition of cytokinesis. PSTPIP is therefore a novel actin-associated protein, potentially involved with cytokinesis, whose tyrosine phosphorylation is regulated by PTP HSCF.

3T3 Cells↗
PubMed1997

Sucralfate for radiation mucositis: results of a double-blind randomized trial.

PURPOSE: To determine if addition of the ulcer-coating polysaccharide sucralfate could improve symptomatic relief of radiation mucositis over a popular combination of antacid, diphenhydramine, and viscous lidocaine alone. METHODS AND MATERIALS: A double-blind study was conducted in which nurses and pharmacists coded patient groups and distributed medication in a manner blinded to both the patients and physicians. Eligible patients receiving radiation to the head and neck and/or chest sites that included the esophagus were randomized to a standard combination of antacid, diphenhydramine, and viscous lidocaine vs. the same solution plus sucralfate. Eligible patients were those receiving >40 Gy at 1.8 Gy/fraction, one fraction/day, five fractions/week. Participating patients were stratified between chest, small field head and neck, and large field head and neck. The patients subjective evaluation of throat soreness and relief with medication was elicited as well as physician observations and smears for Candidiasis screening. Medication was prescribed when the patient became symptomatic and concomitant use of other locally effective nonstudy agents was not allowed. The ability to eat various consistency of foods was graded 0-5, with 5 indicating no compromise of ability to ingest a food compared to baseline. Statistical analysis included mean + SD for food and soreness scores, paired t-test, and two-way analyses of variance to evaluate effects of site and treatment group on the changes in scores. RESULTS: Over 2 years, 111 patients were entered. Because some withdrew and others did not require medication, results are presented for evaluable patients in each category. Mild adverse effects from the medication solution (usually mouth discomfort) were reported by <10% of patients in each treatment group among 106 patients evaluable for toxicity. There was a comparable incidence of mild-moderate mucositis for the two treatment groups. Severe mucositis was noted in two patients of the standard medication group and none among patients receiving sucralfate. The groups were comparable for indicators including degree of soreness, dietary changes, and objective measures or mucosal irritation or infection. For the head and neck patients there was a significant worsening in soreness and in the ability to eat in both treatment groups, whereas patients treated to the chest had less nutritional change. Multivariate analysis including control for confounding factors did not detect treatment effects for any of the response measures. No patient had occult fungal infection detected by oral pathology evaluation of routine mucosal scrapings. CONCLUSIONS: A trend (that was not statistically significant) of less severe radiation mucositis was noted for patients receiving sucralfate in addition to the combination of viscous lidocaine, diphenhydramine, and antacid for nonulcerative radiation mucositis.

Anti-Ulcer Agents↗
PubMed1997

An umbilical metastasis after laparoscopy for squamous cell carcinoma of the cervix.

Laparoscopic surgical techniques are being used with increasing frequency in patients with gynecologic malignancies. Abdominal wall metastases to trochar sites have been described after treatment for ovarian cancer and other adenocarcinomas but are very rare in patients with squamous cell carcinomas. We present a case of metastasis to a laparoscopic trochar site in a patient with squamous cell carcinoma of the uterine cervix. While this may be an unusual event, there is some concern that laparoscopy could disseminate otherwise isolated pelvic disease.

Adult↗
PubMed1997

The effect of valsartan on the angiotensin II pressor response in healthy normotensive male subjects.

OBJECTIVE: Valsartan is an oral antagonist of angiotensin II that competes with angiotensin II for the AT1-receptor and is being developed as an antihypertensive agent. This study assessed the ability of 80 mg valsartan to inhibit the pressor effect of exogenous angiotensin II in healthy normotensive men, first after a single dose and then after multiple doses once daily for 7 days. METHODS: This was a single-center, double-blind, placebo-controlled, randomized crossover study. Six healthy men underwent angiotensin II challenges to determine a suitable dose required to increase their systolic blood pressure by approximately 30 mm Hg. Each subject then received an 80 mg dose of valsartan or matching placebo. The inhibition of the angiotensin II pressor effect was determined by the systolic blood pressure response to repeated angiotensin II challenges at multiple time points. RESULTS: Systolic blood pressure responses to angiotensin II challenges after single and multiple doses of valsartan were significantly lower than placebo, indicating that valsartan blocked the blood pressure response to angiotensin II. The maximum blocking effect was observed within 2 to 3 hours. Mean data suggested that differences in effect between valsartan and placebo were similar after both single and multiple doses and persisted up to 24 hours after administration. The angiotensin II blocking effect was maintained up to this time, despite low plasma valsartan levels and minimal accumulation after multiple doses. CONCLUSION: Valsartan, 80 mg, is a potent angiotensin II antagonist with a rapid onset of action and persistent angiotensin II inhibition up to 24 hours. There is no attenuation of this effect after multiple doses.

Adult↗
PubMed1996

Anterior-inferior capsular length insufficiency in the painful shoulder.

Our clinic's initial attempts to document shoulder capsular laxity made us increasingly aware of the presence of subtle restricted passive shoulder movement in patients with a variety of shoulder diagnoses. The purpose of this study is to describe the evaluation, physical therapy treatment, pathomechanics, and implications of a continuum of anterior-inferior capsular length insufficiency and shoulder pain. One hundred fifty-six patients with the diagnoses of shoulder pain, impingement, rotator cuff tendinitis, and frozen shoulder were found to have capsular length insufficiency and were treated by mobilization techniques deemed as manual decompression. Eighty-three percent displayed good to excellent outcomes for decreasing pain, increasing range of motion, and meeting functional goals. Recent literature has supported the concept that capsular ligaments not only provide restraint, but are specifically oriented to guide and center the humeral head on the glenoid during shoulder movements. These patients presented with abnormal glenohumeral mechanics due to anterior capsular ligament length insufficiency. Glenohumeral ligament length insufficiency can be the primary cause of shoulder pain, ranging from frozen shoulder to impingement-like symptoms. Proper capsular ligament length can be restored with manual techniques. All patients with shoulder pain should have capsular ligament length assessment to ensure proper glenohumeral mechanics.

Adolescent↗
PubMed1995

Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus.

Most patients with non-insulin-dependent diabetes mellitus are resistant to both endogenous and exogenous insulin. Insulin resistance precedes the onset of this disease, suggesting that it may be an initial abnormality. Insulin-receptor kinase activity is impaired in muscle, fibroblasts and other tissues of many patients with non-insulin-dependent diabetes mellitus, but abnormalities in the insulin-receptor gene do not appear to be the cause of this decreased kinase activity. Skin fibroblasts from certain insulin-resistant patients contain an inhibitor of insulin-receptor tyrosine kinase. Here we show that this inhibitor is a membrane glycoprotein, termed PC-1 (refs 10, 11). We find that PC-1 activity is increased in fibroblasts from seven of nine patients with typical non-insulin-dependent diabetes mellitus. In addition, overexpression of PC-1 in transfected cultured cells reduces insulin-stimulated tyrosine kinase activity. These studies raise the possibility that PC-1 has a role in the insulin resistance of non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1995

Regulation of human decidual cell macrophage inflammatory protein-1 alpha (MIP-1 alpha) production by inflammatory cytokines.

PROBLEM: Inflammation of human gestational tissues is a key pathophysiologic event in the genesis of infection-associated preterm labor. Human gestational tissues produce several inflammatory cytokines after stimulation with bacterial products. These include interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), and IL-6. Another class of cytokines includes chemokines of the "C-C" subclassification such as macrophage inflammatory protein-1 alpha (MIP-1 alpha). The purpose of this study was to determine whether cultured human decidual cells produce MIP-1 alpha in response to other inflammatory cytokines. METHODS: Various concentrations of IL-1 beta, TNF alpha, IL-6, and IL-4 were incubated with confluent monolayer cultures of decidual cells isolated from normal term placentae for 16 h at 37 degrees C, and MIP-1 alpha concentrations in culture supernatants were measured by ELISA. RESULTS: We found that incubation of decidual cells with IL-1 beta, TNF alpha, and IL-4 resulted in significant concentration-dependent increases in MIP-1 alpha production. IL-6 had no effect on MIP-1 alpha production. CONCLUSIONS: Our data are the first to show that human decidual cells in culture produce MIP-1 alpha in response to other inflammatory cytokines. We suggest that decidual cell production of MIP-1 alpha is an important early event in the pathophysiology of infection-associated preterm labor.

Cells, Cultured↗
PubMed1995

Invasive electroencephalography in mesial temporal lobe epilepsy.

Invasive EEG recording of spontaneous seizures and correlations of findings with histopathology have defined a characteristic set of electrographic findings in medial temporal lobe epilepsy. The presence of periodic spikes before seizure onset has a significant correlation with reduced CA1 cell counts. This phenomenon is followed, in spontaneous seizures, by 13-25 Hz discharge in medial temporal lobe structures. Temporal neocortical seizure onsets have significantly faster frequencies than hippocampal onsets; hippocampal ictal onset frequencies also vary more often than neocortical onsets. Although hippocampus or entorhinal cortex are involved to a variable degree, the periodic spikes are more consistently seen in hippocampus. Sixty percent of mesial temporal ictal onsets initially propagate to the ipsilateral temporal neocortex. In another 30%, the initial area of propagation is the contralateral hippocampus, to which propagation occurs before involvement of the ipsilateral or contralateral temporal neocortex. Time to propagation of the seizure to the contralateral hippocampus is lengthened in direct proportion to CA4 cell loss, suggesting a role for CA4 in this process. Long interhemispheric propagation times are associated with good surgical outcomes and with the presence of mesial temporal sclerosis. This article also discusses correlation with hippocampal slice physiology, and significance of these findings in understanding the pathophysiology of medial temporal lobe epilepsy.

Electroencephalography↗
PubMed1995

Cisplatin plus radiation therapy.

Advanced-stage squamous cell cancer of the head and neck remains a difficult therapeutic dilemma despite aggressive use of surgery and radiation therapy. The majority of patients still relapse with locoregional disease. Distant metastases are a frequent cause of failure in patients where local disease is controlled. Neoadjuvant chemotherapy reduces the incidence of distant metastasis, but despite the promise generated by a high objective response rate, does not alter the frequency of local recurrence or improve patient survival. The concomitant use of chemotherapy and radiation therapy has the theoretical advantage of radiosensitization with improved local control, preservation of the systemic effect of neoadjuvant treatment, and reduction in the total treatment time. Clinical trials conducted using cisplatin alone or in combination with 5-fluorouracil strongly suggest that this local control advantage is achieved. But randomized studies, convincingly demonstrating that the increased toxicity observed with most concomitant programs is justified by increased patient survival compared with radiation therapy alone, have yet to be completed. Future trials will need to evaluate the impact of cisplatin dose and route of administration. The incorporation into concomitant treatment programs of new agents recently demonstrated as active in head and neck cancer also deserves aggressive clinical investigation.

Antineoplastic Agents↗
PubMed1994

99mTc-DMSA imaging with tomography in renal transplant recipients with abnormal lower urinary tracts.

This study examined whether renal parenchymal imaging using 99mTc DMSA scintigraphy with tomography is a sensitive measure of renal scarring in renal transplant recipients with an abnormal lower urinary tract and whether such scars correlate with impairment of renal function. Three groups of patients were compared: group 1, patients with an abnormal lower urinary tract and deteriorating renal function (n = 9); group 2, abnormal lower urinary tract and stable renal function (n = 5); and group 3, normal lower urinary tract and deteriorating renal function (n = 8). Eight of the nine patients in group 1 had multiple scars visible on 99mTc DMSA scans and this correlated with histology when a renal biopsy was performed; the only patient without scars had a transplant glomerulopathy. The presence of scars was associated with either raised intravesical pressures or recurrent urinary tract infections (UTIs). Only one patient in each of groups 2 and 3 had visible scars and both these patients had a history of recurrent UTIs. Patients in group 3 with deteriorating renal function due to chronic rejection documented by biopsy did not have cortical scars visible with 99mTc DMSA tomography. 99mTc DMSA scanning with tomography is a useful investigation in the management of renal transplant patients with declining renal function; multiple scars may indicate abnormal lower urinary tract function and are not seen in chronic rejection.

Cicatrix↗
PubMed1993

Purification, receptor binding analysis, and biological characterization of human melanoma growth stimulating activity (MGSA). Evidence for a novel MGSA receptor.

Human melanoma growth stimulating activity (MGSA) is a mitogenic factor first identified in the conditioned media of human melanoma cells. Structurally, MGSA belongs to a superfamily of proteins that includes interleukin-8 (IL-8) and platelet factor 4. These proteins are involved in inflammatory processes, and an understanding of their mechanism of action should provide insight into their pathophysiology. In this study, we report the high level expression of recombinant human MGSA in Escherichia coli. The structure was confirmed by mass spectrometry and NH2-terminal amino acid sequencing. Receptor binding studies were carried out in a human melanoma cell line, Hs294T, and in U937 cells. Direct binding experiments with 125I-MGSA in Hs294T cells have allowed us to identify a novel MGSA receptor in these cells, with a KD of 3.9-4.25 nM and approximately 52,960-67,758 binding sites/cell. These MGSA-binding sites were specific and could not be displaced by unlabeled IL-8. The MGSA receptor in these cells is biologically active, and the addition of ligand induces cellular proliferation in a dose-dependent manner. In U937 cells, unlabeled IL-8 and MGSA were able to completely displace radiolabeled IL-8. Scatchard analysis of the displacement binding data was consistent with binding to a single class of binding sites, and the calculated KD values were 2.4 +/- 0.6 nM for IL-8 and 3.2 +/- 0.80 nM for MGSA. Treatment of U937 cells with IL-8 or MGSA produced a rapid increase in Ca2+ flux; however, subsequent incubation with either ligand failed to produce any further Ca2+ flux. The IL-8 receptor in U937 cells was covalently labeled with 125I-IL-8 to reveal a protein with a molecular mass of 69 kDa.

Amino Acid Sequence↗
PubMed1993

Nucleolar organiser regions in odontogenic cysts and ameloblastomas.

Silver nucleolar organiser region (AgNOR) counts were performed on apical periodontal cysts, dentigerous cysts, odontogenic keratocysts, ameloblastomas and basal cell carcinomas. Significant differences, but with excessive overlap, were shown between dentigerous cysts and apical periodontal cysts and between odontogenic keratocysts and apical cysts. The mean AgNOR counts for all odontogenic cysts ranged between 2.02 and 2.65, and for ameloblastomas were 2.24, indicating that the method has neither a diagnostic nor a prognostic value in these lesions. Control oral squamous cell carcinoma tissues had significantly higher AgNOR counts than any other lesion tested.

Ameloblastoma↗
PubMed1992

Paediatric renal transplantation in Ireland: 1980-1990.

Between 1980 and 1990, 862 renal transplants were performed at our unit. Forty-six of these were given to 38 children. The mean age of the children was 8.6 years. Reflux nephropathy accounted for 39% of the primary renal diseases, followed by congenital disorders (30%), and glomerulonephritis (16%). Seventy percent of the grafts were from cadaveric donors. The one year patient survival was 90%, and the one year graft survival 61%. Seven children received a second graft with a one year graft survival of 71%.

Adolescent↗
PubMed1992

Cytomegalovirus infection as a complication of OKT3 therapy in kidney transplant recipients.

We compared the incidence of clinical CMV illness in 25 renal transplant recipients treated with OKT3 for steroid resistant cellular rejection with 88 renal transplant patients treated only with conventional immunosuppression (cyclosporin A and steroids). Nine (36%) patients in the OKT3 group developed CMV illness compared to (2.3%) amongst those treated conventionally (p < 0.0005). Patients who received OKT3 were divided into four groups according to the CMV antibody status of the donor and recipient. Six of the 9 episodes of CMV infection occurred in patients not previously exposed to CMV, who received a kidney from a CMV positive donor. Three (12%) of the patients treated with OKT3 died of CMV disease. A further 2 patients died of other causes giving an overall mortality in the OKT3 treated group of 20%. We concluded that when OKT3 therapy is used in association with donor/recipient CMV mismatch it is associated with a high CMV morbidity and mortality.

Adolescent↗