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Biomedical subjects

L Anderson

Publications and source records attributed to L Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Mycophenolate mofetil reduces the risk of acute rejection less in African-American than in Caucasian kidney recipients.

BACKGROUND: Multicenter clinical trials have shown that mycophenolate mofetil (MMF) reduces the risk of acute rejection, but it is unknown whether African-Americans constitute a subgroup of recipients less likely to benefit from MMF. METHODS: This study compared the acute rejection rates within 6 months of kidney transplantation in MMF-treated transplant patients with those on azathioprine (AZA) at a single center. The study population consisted of 353 consecutive recipients of cadaver or living donor kidney transplants. African-Americans constituted 43% of the patients on AZA and 49% of the patients on MMF. Variables used in a Cox regression analysis included MMF immunosuppression, recipient race, type of transplant, delayed graft function, postoperative immune induction, average cyclosporine trough level, and HLA mismatch. RESULTS: Significantly fewer patients on MMF experienced a biopsy-proven rejection episode than those treated with AZA (24% vs. 42%, respectively; relative risk [RR]=0.57, P=0.001). This decrease in risk was greater in Caucasian transplant recipients (MMF vs. AZA: 16% vs. 46%, RR=0.35, P < 0.001) than in African-American patients (32% vs. 36%, RR=0.88, P=0.6). Within each race stratum, the mean cyclosporine trough levels averaged over 2-week intervals were nearly identical for AZA- compared with MMF-treated patients. In the regression model, the effect of MMF on the incidence of rejection was again less in African-American than in Caucasian patients. CONCLUSIONS: Kidney recipients treated with MMF have a significantly lower risk of acute rejection within 6 months of transplantation than those given AZA. This reduction in risk is significantly less in African-American recipients than Caucasians.

Adult↗
PubMed1998

Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene.

Mutations in the presenilin genes (PS-1 and PS-2) cause early onset autosomal dominant Alzheimer's disease (AD). Eight early-onset, autopsy-documented familial AD kindreds were screened for mutations in PS-1, and seven different mutations were identified. Three of these were new mutations (G209V, A426P, and E120D), two were previously reported mutations in new families, and three mutations were confirmed in previously published families. Two of these new mutations are found within predicted transmembrane domains (TMDs 4, 7, and 8). The A426P mutation is the most C-terminal PS-1 mutation identified to date.

Adult↗
PubMed1998

Tau is a candidate gene for chromosome 17 frontotemporal dementia.

Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17), a recently defined disease entity, is clinically characterized by personality changes sometimes associated with psychosis, hyperorality, and diminished speech output, disturbed executive function and nonfluent aphasia, bradykinesia, and rigidity. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, and amygdala. Neurofibrillary tangles (NFTs) are seen in some but not all families. Inheritance is autosomal dominant and the gene has been regionally localized to 17q21-22 in a 2- to 4-centimorgan (cM) region flanked by markers D17S800 and D17S791. The gene for tau, the primary component of NFTs, is located in the same region of chromosome 17. Tau was evaluated as a candidate gene. Physical mapping studies place tau within 2 megabases or less of D17S791, but it is probably outside the D17S800-D17S791 FTDP-17 interval. DNA sequence analysis of tau coding regions in affected subjects from two FTDP-17 families revealed nine DNA sequence variants, eight of which were also identified in controls and are thus polymorphisms. A ninth variant (Val279Met) was found in one FTDP-17 family but not in the second FTDP-17 family. Three lines of evidence indicate that the Val279Met change is an FTDP-17 causative mutation. First, the mutation site is highly conserved, and a normal valine is found at this position in all three tau interrepeat sequences and in other microtubule associated protein tau homologues. Second, the mutation co-segregates with the disease in family A. Third, the mutation is not found in normal controls.

Chromosome Mapping↗
PubMed1998

Enkephalin-processing oligopeptidases in cobra venom: inhibition by thiorphan and bestatin reveals co-operative actions.

The peptidase inhibitors thiorphan and bestatin were tested for their ability to inhibit the actions of the oligopeptidases contained in the venom of the Taiwan cobra (Naja naja atra). With methionine enkephalin (TyrGlyGlyPheMet) as substrate, thiorphan was an effective inhibitor of cleavage of the GlyPhe peptide bond while bestatin inhibited cleavage of the TyrGly peptide bond. Thiorphan and bestatin also inhibited subsequent cleavage of the fragments GlyGlyPheMet and TyrGlyGly respectively. These inhibitors reveal an interplay between the venom oligopeptidases in which the enzymes provide additional substrates for each other following their initial competitive attack on the neuropeptide. A possible explanation is that the system is intended to ensure a steady release of Tyr, GlyGly and PheMet over time. Significantly, Tyr is the favoured substrate of the L-amino acid oxidase present in the venom, which rapidly transforms this aromatic amino acid into phenolic derivatives. The efficacies of these inhibitors also suggest that there are similarities between the venom oligopeptidases and the peptidases associated with the processing of enkephalin in its normal contexts.

Aminopeptidases↗
PubMed1998

Conversion of tyrosine to phenolic derivatives by Taiwan cobra venom.

We have examined the ability of Taiwan cobra (Naja naja atra) venom to transform in vitro the amino acid tyrosine to phenolic oxidation products via 4-hydroxyphenylpyruvate. This amino acid can be released from neuropeptide substrates by oligopeptidases present in the venom. Using a variety of analytical techniques to probe a complicated series of reactions, we confirm that the L-amino acid oxidase present in the venom initially releases the keto form of 4-hydroxyphenylpyruvic acid and hydrogen peroxide after reacting with the tyrosine. Thereafter, there is evidence that a tautomerase in the venom promotes a partial conversion of the keto-form 4-hydroxyphenylpyruvic acid into an enol form. The enol is oxidised primarily to 4-hydroxybenzaldehyde and 4-hydroxyphenol (hydroquinone). The keto form is oxidised through to 4-hydroxyphenylacetic acid by the hydrogen peroxide co-released by the L-amino acid oxidase. The venom promotes both these spontaneous oxidation routes and also generates traces of other phenolics, some of which are as yet unidentified. We propose that reactions between the precursors of the major oxidation products may be responsible for generating unusual short-lived phenolics, possibly giving rise to special bioactivities that are relevant to venom action.

Amino Acid Sequence↗
PubMed1998

Development and evaluation of a new alcohol-based surgical hand scrub formulation with persistent antimicrobial characteristics and brushless application.

BACKGROUND: Since the introduction in the 1970s of surgical hand scrub formulations that contain 4% chlorhexidine gluconate (CHG), new surgical scrub formulations that have improved efficacy, persistence, or significantly improved use characteristics have not been forthcoming. In addition, the manufacturer's labeling for popular hand scrub products generally requires scrub times in excess of 6 minutes, whereas current practical needs call for products with substantially shorter scrub times. A new alcohol-based surgical scrub formulation, which has ingredients that provide emollient, surfactant, and antimicrobial persistence characteristics to complement the rapid and broad-spectrum antiseptic qualities of alcohol, has been developed in an effort to address these current practical needs. METHODS: The relative efficacy of a new alcohol-based surgical scrub formulation that contains ingredients that provide surfactant and antimicrobial persistence characteristics was compared with that of commercial 4% CHG and 7.5% povidone iodine (PVPI) formulations with use of human subjects. Hand antimicrobial count sampling was performed by using standardized "glove juice" methodology. RESULTS: The efficacy and persistence results of the new formulation showed statistically significant improvement over both CHG and PVPI at a substantially lessened scrub time (3 minutes). In addition, use of the new formulation without a scrub brush produced results statistically similar to 3-minute applications with either a brush or a sponge. CONCLUSIONS: The new alcohol-based formulation demonstrates promise as a new surgical hand scrub formulation with antimicrobial and use characteristics that are significantly improved over current CHG and PVPI formulations. These studies demonstrate the suitability of this formulation for use as a surgical hand scrub and for brushless application.

Administration, Topical↗
PubMed1998

A comparison of midazolam co-induction with propofol predosing for induction of anaesthesia.

In a double-blind, placebo-controlled study of 90 ASA 1 and 2 patients scheduled for elective surgery we compared the effect of pre-administering midazolam 2 mg or propofol 30 mg on the dose of propofol subsequently required to induce anaesthesia. Using loss of response to verbal command and tolerance to placement of a facemask as end-points, the dose of propofol required to induce anaesthesia was significantly smaller in the patients given propofol (1.87 mg.kg-1) or midazolam (1.71 mg.kg-1) when compared to the control group (2.38 mg.kg-1). Although the decrease in blood pressure following induction was no difference between the two study groups and the decrease was felt not to be of clinical significance in this group of patients. As propofol is presented ' ... for use in a single patient only' and the technique of predosing with propofol allowed induction of all patients with less than 200 mg (a single ampoule), we question on a cost basis whether midazolam co-induction is necessary to reduce propofol induction doses.

Adjuvants, Anesthesia↗
PubMed1998

The effects of coital lubricants on sperm motility in vitro.

Infertility affects approximately 15% of couples, and in about one-third the primary cause is a male factor. Patients undergoing infertility investigations frequently experience sexual dysfunction, which often is due to inadequate vaginal lubrication. This can lead to increased use of coital lubricants. The effects of such lubricants on sperm motility have not been widely studied, although sperm motility is one of the best prognostic indicators of fertilization. Using a prospective longitudinal control-based study, we analysed the effect of adding four lubricants: KY jelly, baby oil, olive oil and saliva on sperm motion in 16 samples from patients undergoing infertility investigations. Sperm samples were prepared by density gradient centrifugation prior to mixing with lubricants. Motility parameters were determined using computer-assisted semen analysis after 5, 15 and 30 min. All lubricants except baby oil significantly decreased percentage progressive motility, progressive velocity, curvilinear velocity and lateral head displacement at 12.5% concentration. At a lower concentration of 6.25%, both olive oil and saliva still significantly reduced progressive motility parameters, while KY jelly diminished head movement parameters. Hence, even at these very low concentrations, coital lubricants impair sperm motility and thus may adversely affect fertility.

Cellulose↗
PubMed1998

Concomitant irradiation and dose-escalating carboplatin for locally advanced carcinoma of the uterine cervix: an updated report.

The combination of radiotherapy and carboplatin is associated with high response rates among women who have cervical cancer. To improve control rates for patients who have locally advanced carcinoma of the uterine cervix, oncologists have explored combinations of radiotherapy and chemotherapy. Carboplatin is an analogue of cisplatin, with similar efficacy against cervix cancer and a toxicity profile that is theoretically appealing for this group of patients because it is not nephrotoxic. Fifteen women with International Federation of Gynecology and Obstetrics (FIGO) stages IB2 through IIIB or recurrent carcinoma of the cervix were treated with megavoltage irradiation and weekly intravenous carboplatin (7 women, 60 mg/m2; 8 women, 90 mg/m2). Response was documented among all patients treated at 60 mg/m2 (three complete responses, four partial responses) and in 6 women treated with 90 mg/m2 (four complete responses, two partial responses). The two nonresponders in the series presented with recurrent glassy cell carcinoma of the cervix. All patients completed the planned course of therapy without the need for treatment interruption. At 60 mg/m2, one dose of carboplatin was withheld because of grade 2 thrombocytopenia. At 90 mg/m2, one case of grade 2 leukopenia was documented. The leukocyte counts remained within normal limits for all 3 patients who were irradiated through extended portals that encompassed the paraaortic nodes (2 women, 60 mg/m2; 1 woman, 90 mg/m2). To date, 2 of 7 patients treated at the lower dose level have died of disease (one local progression and distant failure at 11 months, one distant failure alone at 6 months). The remaining patients treated at 60 mg/m2 are alive at a median of 24 months (range, 21-37 months). Among those treated at the higher dose level, 1 patient is alive with local and distant failure at 14 months, and 1 woman succumbed to local and distant disease at 4 months. The remainder are alive at a median follow-up of 6 months (range, 2-10 months). The regimen was unsuccessful in salvaging women with recurrent glassy cell carcinoma. We conclude that the combination of radiotherapy and carboplatin can be safely delivered at both of the chemotherapy schedules studied. The regimen should not be offered to women who have recurrent glassy cell tumors. To prove the efficacy of this approach, phase III testing should be considered that compares the combination of agents to irradiation alone.

Adult↗
PubMed1998

Agonist-induced endocytosis and recycling of the gonadotropin-releasing hormone receptor: effect of beta-arrestin on internalization kinetics.

This study examined the dynamics of endocytotic and recycling events associated with the GnRH receptor, a unique G protein-coupled receptor (GPCR) without the intracellular carboxyl-terminal tail, after agonist stimulation, and investigated the role of beta-arrestin in this process. Subcellular location of fluorescently labeled epitope-tagged GnRH receptors stably expressed in HEK 293 cells was monitored by confocal microscopy, and the receptor/ligand internalization process was quantified using radioligand binding and ELISA. Agonist stimulation resulted in reversible receptor redistribution from the plasma membrane into the cytoplasmic compartment, and colocalization of internalized GnRH receptors with transferrin receptors was observed. Internalization experiments for the GnRH receptor and another GPCR possessing a carboxy-terminal tail, the TRH receptor, showed that the rate of internalization for the GnRH receptor was much slower than for the TRH receptor when expressed in both HEK 293 and COS-7 cells. TRH receptor internalization could be substantially increased by coexpression with beta-arrestin in COS-7 cells, while GnRH receptor internalization was not affected by coexpression with beta-arrestin in either cell type. Coexpression of the GnRH receptor with the dominant negative beta-arrestin (319-418) mutant did not affect its ability to internalize, and activated GnRH receptors did not induce time-dependent redistribution of beta-arrestin/green fluorescent protein to the plasma membrane. However, the beta-arrestin mutant impaired the internalization of the TRH receptor, and activated TRH receptors induced the beta-arrestin/green fluorescent protein translocation. This study demonstrates that, despite having no intracellular carboxy-terminal tail, the GnRH receptor undergoes agonist-stimulated internalization displaying distinctive characteristics described for other GPCRs that internalize via a clathrin-dependent mechanism and recycle through an acidified endosomal compartment. However, our data indicate that the GnRH receptor may utilize a beta-arrestin-independent endocytotic pathway.

Animals↗
PubMed1998

Mechanisms of progressive glomerular injury in membranous nephropathy.

Glomerular function and structure were serially evaluated in 15 patients with membranous nephropathy who exhibited relapsing nephrosis and chronic depression of GFR. GFR declined from 56+/-8 (mean+/-SEM) at onset to 31+/-4 ml/min per 1.73 m2 after a 2- to 5-yr period of observation (P < 0.05). An analysis of filtration dynamics suggested persistent elevation of net ultrafiltration pressure. To examine a possible role for declining intrinsic glomerular filtration capacity as the basis for the observed hypofiltration, glomeruli in the baseline and a repeat biopsy (performed after a median of 28 mo) were subjected to morphometric analysis and mathematical modeling. Analysis of the baseline biopsy revealed a reduction in filtration slit frequency and thickening of the glomerular basement membrane, lowering computed hydraulic permeability by 66% compared with normal kidney donors. In contrast, filtration surface area was increased by 37% as a result of glomerular hypertrophy. The repeat biopsy revealed persistent depression of hydraulic permeability, primarily owing to foot process broadening. An additional finding was a decrease in filtration surface area from baseline in patent glomeruli, possibly due to encroachment on the capillary lumen of an increasingly widened basement membrane. Also, a striking increase in the prevalence of global glomerulosclerosis from 7+/-2% to 23+/-4% was found between the two biopsies, suggesting a significant loss of functioning nephrons. It is concluded that hypofiltration in membranous nephropathy is the consequence of a biphasic loss of glomerular ultrafiltration capacity, initially owing to impaired hydraulic permeability that is later exacerbated by a superimposed loss of functioning glomeruli and of filtration surface area.

Adult↗
PubMed1998

Evaluating cervical neoplasia. LEEP as an alternative to cold knife conization.

OBJECTIVE: To determine how the loop electrosurgical excision procedure (LEEP) compares to cold knife conization in providing an adequate diagnostic specimen. STUDY DESIGN: Between 1991 and 1995, 95 patients underwent either diagnostic LEEP or cold knife conization at Allegheny University Hospitals. The indications for the procedure were a cytologic/histologic discrepancy, unsatisfactory colposcopic evaluation, positive endocervical curettage or exclusion of invasion. RESULTS: Severe thermal artifact rendered the LEEP specimens uninterpretable in 4.4% of cases. A median number of two passes were required for LEEP excision of the transformation zone. The number of passes correlated with the amount of thermal artifact detected (P = .034). Regarding recurrence patterns, normal follow-up cervical cytology was similar for both groups: 96.7% in the LEEP group vs. 100% in the cold knife conization group. CONCLUSION: We conclude that LEEP is an acceptable diagnostic alternative to traditional cold knife conization. Thermal artifact remains a disadvantage that can be minimized by limiting the number of passes required to obtain a complete specimen.

Adolescent↗
PubMed1997

A novel approach to the treatment of chronic allograft nephropathy.

BACKGROUND: Progressive deterioration of renal function in kidney transplant recipients is the leading cause of graft failure. Both nonimmunologic and immunologic mechanisms contribute to this deterioration. METHODS: Twenty-eight cyclosporine (CsA)-treated renal transplant recipients (21 cadaveric, 5 living, 2 simultaneous kidney-pancreas) with progressive deterioration of renal function were prospectively enrolled in a clinical trial and had their immunosuppressive regimen changed 24.3+/-7.7 months after transplant. All patients had their CsA dose reduced by 50%, azathioprine was discontinued, and mycophenolate mofetil was added to the medical regimen. The mean creatinine of the patients at the initiation of the change in immunosuppression was 3.5+/-1.2 mg/dl (range 1.9 to 6.2 mg/dl). RESULTS: Before the change in immunosuppression, the mean loss in renal function as indicated by the least-squares slope of the reciprocal of creatinine versus time was -0.006+/-0.002 (mg/dl)-1 per month. The change in immunosuppression significantly decreased the rate of loss in renal function for most patients when compared with their pretreatment values with a mean slope of 0.007+/-0.003 (mg/dl)-1 per month (P=0.003). Renal function improved in 21 of 28 patients. Only one patient had continued deterioration of renal function. In a multivariate analysis adjusting for CsA dose, mean arterial blood pressure, and baseline creatinine, the change in immunosuppression was significantly associated with improved renal function (P=0.02). There were no acute rejections after the immunosuppression change. CONCLUSIONS: We conclude that adding mycophenolate mofetil and reducing CsA in patients with chronic deterioration of graft function is well tolerated and results in a short-term improvement in renal function.

Adult↗
PubMed1997

Quality assurance of stem cell enumeration by flow cytometry. Canadian QASE Study Group.

The enumeration of CD34+ cells by flow cytometry is commonly employed to assess progenitor/stem cell numbers in peripheral blood, cord blood, and apheresis products used for peripheral blood stem cell transplantation (PBSCT). Until recently, the enumeration of CD34+ cells has evolved in the absence of any procedural guidelines or quality assurance programs. We established a voluntary quality assurance for stem cell enumeration (QASE) program for Canadian laboratories involved in PBSCT. The goals of this study were 1) to survey current flow cytometric procedures for CD34 enumeration; 2) to evaluate inter-institutional reproducibility of currently employed assays; and 3) to evaluate the impact of adoption of a common method on inter-laboratory variability. Fourteen to nineteen laboratories participated in this program by enumerating CD34+ cells in shared cord blood samples. The survey showed a wide variation in flow cytometric methodology which in part contributed to the wide range in results obtained between different centres. Major differences in methodology included the number of events counted, use of isotype control and gating strategy. Participation in this program and adoption of a common methodology increased level of agreement for any given result although this trend did not reach statistical significance (P = 0.13). The results of this survey emphasize the need for a quality assurance program for stem cell enumeration by flow cytometry.

Antigens, CD34↗
PubMed1997

Identification and characterization of a pro-tumor necrosis factor-alpha-processing enzyme from the ADAM family of zinc metalloproteases.

Tumor necrosis factor-alpha (TNF) is initially expressed as a 26-kDa membrane-bound precusor protein (pro-TNF) that is shed proteolytically from the cell surface, releasing soluble 17-kDa TNF. We have identified human ADAM 10 (HuAD10) from THP-1 membrane extracts as a metalloprotease that specifically clips a peptide substrate spanning the authentic cleavage site between Ala76 and Val77 in pro-TNF. To confirm that HuAD10 has TNF processing activity, we cloned, expressed, and purified an active, truncated form of HuAD10. Characterization of recombinant HuAD10 (rHuAD10) suggests that this enzyme has many of the properties (i.e. substrate specificity, metalloprotease activity, cellular location) expected for a physiologically relevant TNF-processing enzyme.

ADAM Proteins↗
PubMed1997

Partial reversal of heparin anticoagulation by intravenous protamine in abciximab-treated patients undergoing percutaneous intervention.

Serious hemorrhage and vascular complications after abciximab therapy are associated with elevated activated clotting time values. Our preliminary experience suggests that low-dose intravenous protamine administration is both safe and effective in reducing elevated in-laboratory activated clotting time values and the potential for serious hemorrhage in abciximab-treated patients.

Abciximab↗