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J R Young

Publications and source records attributed to J R Young.

At least 37 records · Page 2Linked to original sources
PubMed1997

The pathological and biological nature of screen-detected breast carcinomas: a morphological and immunohistochemical study.

Traditional and immunohistochemical markers of prognosis were examined in 455 mammary carcinomas derived from breast cancer screening and compared with those of 277 carcinomas presenting symptomatically over the same period. Tumours detected by population screening under the U.K. National Health Service Programme do not differ from those detected by other screening projects, but compared with symptomatic cancers, screen-detected cancers are more likely to be in situ and if invasive, to be smaller, of lower grade, and to have invaded vessels, perineural spaces, and lymph nodes less frequently. Tubular and cribriform types are more often represented in screened patients. Immunohistochemical markers which have been proposed as being related to likely tumour behaviour (epidermal growth factor receptor, c-erbB-2 protein, oestrogen and progesterone receptors, cathepsin D, p53, and retinoblastoma protein) do not distinguish screen-detected from 'clinical' cancers. It is concluded that cancers diagnosed at screening do not differ biologically from those presenting clinically, but are the same lesions detected at an earlier stage of their natural history.

Biomarkers, Tumor↗
PubMed1997

Polymorphism of chicken CD8-alpha, but not CD8-beta.

We report here the structural basis of CD8 polymorphism in the chicken. Three chicken strains (RPRL Line 7, H.B15.H7, and H.B15. H12) have 14 nucleotide differences in the CD8A cDNA sequence causing eight amino acid replacements in the extracellular part of the molecule. Only two amino acid replacements and four silent mutations were observed in the CD8B cDNA sequence in one (H7) of the strains. Substitutions in CD8alpha were solely responsible for the binding of CD8-specific monoclonal antibodies, as detected by cDNA expression in COS cells. The majority of the amino acid substitutions are located in the immunoglobulin V-like domain and three of the changes (residues 30, 34, and 58) are situated in the putative major histocompatibility complex class I binding CDR1 and CDR2 regions of the chicken CD8alpha. CD8A polymorphism has not been reported in other species and this suggests that CD8A and CD8B have evolved under different selective pressures in the chicken.

Amino Acid Sequence↗
PubMed1997

Carotid endarterectomy in adults 50 years of age and younger: a retrospective comparative study.

PURPOSE: Atherosclerotic carotid artery stenosis (CAS) is the most common cause of stroke in young adults. We retrospectively studied clinical characteristics of premature CAS and the safety and durability of carotid endarterectomy (CEA) in 56 patients 50 years of age or younger (mean, 46.4 years; 34 (60%) males; group I) who underwent primary CEA at the Cleveland Clinic between 1983 and 1993. METHODS: The patients were identified from the Vascular Surgery Registry and were compared with 202 randomly selected patients 60 years of age and older (mean, 69.3 years; group II) who were frequency-matched by gender and the year of primary CEA. Carotid shunting was used routinely, and the arteriotomy was patched in the majority of cases. Patients were followed-up for mean of 47.2 months (group I) and 46.0 months (group II). RESULTS: No significant differences were found in the indications for CEA (symptomatic CAS, 49% in group I vs 48% in group II) or the prevalence of diabetes, coronary diseases, and lower extremity arterial disease. Younger adults were more likely to have a history of smoking (93% vs 76%; p = 0.005), hypertension (71% vs 52%; p = 0.006), premature menopause (57% vs 18%; p < 0.001) and had lower levels of high-density lipoprotein cholesterol (p = 0.03). There were no in-hospital deaths. Perioperative strokes in the distribution of the operated artery occurred within 24 hours in one younger patient (1.8%) and in one older patient (0.5%). This was attributed to early carotid thrombosis in the young patient. Major late postoperative neurologic complications were documented in one young patient (1.8%) and six older patients (3%). Patients in group I were at significantly higher risk for recurrent carotid stenosis (risk ratio, 3.1; 95% confidence interval [CI], 1.3 to 7.3; p = 0.010); younger individuals remained at significantly higher risk for recurrent stenosis even after adjusting for smoking and hypertension (risk ratio, 3.7; 95% CI, 1.5 to 9.4; p = 0.006). By life-table analysis, younger adults tended to have a higher rate of late reoperations (p = 0.065). CONCLUSIONS: CEA can be safely performed in young adults with premature CAS, although younger individuals appear to have higher rates of recurrent carotid stenosis compared with older counterparts.

Adult↗
PubMed1997

High incidence of restenosis/reocclusion of stents in the percutaneous treatment of long-segment superficial femoral artery disease after suboptimal angioplasty.

PURPOSE: To evaluate the efficacy of intravascular stents used to treat long-segment stenoses and occlusions of the superficial femoral artery (SFA) after suboptimal angioplasty. METHODS: Fifty-eight limbs in 55 patients who underwent stenting of the SFA were identified from a vascular registry. Indications for stent placement after suboptimal PTA included flow-limiting dissection, residual pressure gradient (>15 mm Hg) or stenosis (>30%), or failure to establish initial patency. Lesion length ranged from 6 to 35 cm (mean, 16.5 cm). Endpoints for primary patency were: restenosis of >50%, reocclusion, or diminution of the postprocedure ankle-brachial index greater than 0.15. RESULTS: The mean ankle-brachial index improved from 0.48 +/- 0.19 to 0.71 +/- 0.23 (p = 0.001). Primary patency rates by Kaplan-Meier estimates at 1 month, 6 months, and 1 year were 88%, 47%, and 22%, respectively. Secondary patency rates were 94% at 1 month, 59% at 6 months, and 46% at 1 year. The median time to reaching an endpoint of restenosis or reocclusion was 6 months primarily and 9 months secondarily. Clinical improvement at the time of latest follow-up occurred in 56% of patients (mean, 13.8 months). Periprocedural complications occurred in 24.5% of patients with the first intervention. The only factor that favorably influenced outcome was improvement in clinical category after the procedure (p = 0.001). CONCLUSIONS: There was a high incidence of restenosis and reocclusion with long-segment SFA disease that required stents to achieve initial success. Despite close surveillance and reintervention, anatomic patency at 1 year was poor. However, clinical benefit was maintained in the majority of patients. The outcome was similar in the claudication population compared with those who had limb-threatening ischemia. Percutaneous revascularization of long-segment SFA disease requiring stents should be reserved for patients with critical limb ischemia for which no reasonable surgical alternative exists.

Adult↗
PubMed1996

Concordance of preoperative clinical risk with angiographic severity of coronary artery disease in patients undergoing vascular surgery.

BACKGROUND: Preoperative clinical indexes to stratify cardiac risk have not been validated angiographically. Our aims were to determine the concordance of clinical risk with severity of coronary stenosis and to develop and validate a preoperative clinical index to exclude the presence of significant coronary stenosis. METHODS AND RESULTS: We carried out a prospective study of 878 consecutive patients (including the derivation and validation sets). "Severe" stenosis was defined as three-vessel (> or = 50% stenosis in each), two-vessel (> or = 50% stenosis in one when the other is > or = 70% stenosis of the left anterior descending), or left main disease (> or = 50%); "critical" stenosis was three-vessel (> or = 70% stenosis in each) and/or left main stenosis > or = 70%. A preoperative clinical index (diabetes mellitus, prior myocardial infarction, angina, age > 70 years, congestive heart failure) was used to stratify patients. A gradient of risk for severe stenosis was seen with increasing numbers of clinical markers. The following prediction rules were developed: The absence of severe coronary stenoses can be predicted with a positive predictive value of 96% for patients who have no (1) history of diabetes, (2) prior angina, (3) previous myocardial infarction, or (4) history of congestive heart failure. The absence of critical coronary stenoses can be predicted with a positive predictive value of 94% for those who have no (1) prior angina, (2) previous myocardial infarction, or (3) history of congestive heart failure. CONCLUSIONS: By reliably identifying a large proportion of patients with a low likelihood of significant stenoses, these prediction rules can help to substantially reduce healthcare costs associated with preoperative cardiac risk assessment for noncardiac surgery.

Aged↗
PubMed1996

Angiographic correlates of cardiac death and myocardial infarction complicating major nonthoracic vascular surgery.

In a case-control study of 63 patients undergoing major nonthoracic vascular surgery with prior cardiac catheterization, we found total coronary occlusion serving viable myocardium and "nonobstructive" lesions to be the most common proximate cause of perioperative myocardial infarction or death. The extent of coronary disease by several measures was significantly correlated with adverse outcome, and prior bypass surgery appeared to be protective.

Aged↗
PubMed1996

Chicken B-cell marker chB6 (Bu-1) is a highly glycosylated protein of unique structure.

The chB6 molecule is expressed on chicken B cells throughout most of their development, as well as on some non-lymphoid cells. It has long been used as an allotypic marker in important studies of B-cell development, though its function is unknown. We isolated a chB6 cDNA by expression cloning and sequenced two further alleles following polymerase chain reaction amplification. The results show that chB6 is a typical type I transmembrane protein, highly glycosylated in the extracellular region and carrying a large intracellular region. It has no recognizable similarity to known mammalian molecules and thus represents a unique B-cell marker. Its presence in chickens may be related to differences in the properties of B-cell development between chickens and mammalian species. The sequences of the different alleles of this gene revealed a higher level of polymorphism than expected. A restriction fragment length polymorphism linked to the CHB6 gene has been used to determine its location on the linkage map of the chicken genome, which will allow the definitive evaluation of reported associations with disease resistance.

Amino Acid Sequence↗
PubMed1996

Ultrasound-guided compression closure of postcatheterization pseudoaneurysms during concurrent anticoagulation: a review of seventy-seven patients.

PURPOSE: Data from our institution and elsewhere have demonstrated that ultrasound-guided compression closure (UGCC) is an effective method of treating postcatheterization pseudoaneurysms. Whereas patients receiving anticoagulation do not have as high a success rate as those not receiving anticoagulants, there have been no large series evaluating the factors associated with success or failure in patients receiving anticoagulation. The purpose of this study is to determine whether uninterrupted anticoagulation interferes with successful UGCC of pseudoaneurysms and to identify factors associated with success or failure. METHODS: From May 1991 to September 1994, 238 cases of attempted UGCC of pseudoaneurysms were performed in our vascular laboratory. Only patients who received uninterrupted heparin, warfarin, or both at the time of pseudoaneurysm compression were eligible for inclusion into the study. Seventy-seven patients were identified who met the study criteria. RESULTS: Successful pseudoaneurysm compression was obtained in 56 (73%) patients, whereas 21 (27%) patients had a failed UGCC. In the successfully treated group, seven (12.5%) required between two to three compression attempts to induce sustained thrombosis. There was no statistical difference in age, sex, sheath size, days after procedure, location of pseudoaneurysm, or number of chambers in the pseudoaneurysm between those patients who had a successful repair and those who did not. If the pseudoaneurysm was less than 4 cm in diameter, 51 of 65 patients (78%) had a successful repair compared with 5 of 12 patients (42%) with a pseudoaneurysm of 4 cm or greater (p = 0.013). There was no statistical difference between success and failure in patients receiving warfarin alone (3.73 mean international normalized ratio, 72% success rate), heparin alone (mean activated partial thromboplastin time of 63 seconds, 92% success rate), or heparin and warfarin (mean activated partial thromboplastin time of 70 seconds, mean international normalized ratio of 4, success rate of 67%). No arterial or venous thrombosis occurred during pseudoaneurysm compression. CONCLUSION: Successful UGCC of pseudoaneurysms occurred in a large percentage of patients receiving full-dose, uninterrupted anticoagulation. The only factor influencing success was the size of the pseudoaneurysm.

Adult↗
PubMed1996

Examination of multidrug resistance in cell lines and primary breast tumours by flow cytometry.

The aim of this study was to measure multidrug resistance (MDR) by flow cytometry and quantify the expression of P-glycoprotein (using antibody) glutathione transferase (using alpha-GSTpi antibody) in alpha-JSB-1 and alpha-GSTpi of a series of cell lines and primary breast cancers, and to assess the relationship between these MDR proteins and a selection of oncogene and prognostic markers in breast cancer. Flow cytometry was performed using permeabilised cells stained with fluorescent antibodies using well-established methods. Antibody staining was confirmed for JSB1, but not GSTpi by use of known positive and negative controls. No correlation was seen when comparing the number of molecules of alpha-JSB-1 with alpha-GSTpi (P = 0.1, r2 = 0.4, n = 14) using a selection of cell lines. Examination of 45 breast tumours for expression of JSB-1 and GSTpi revealed a significant association between these two antibodies (P < 0.00001, r2 = 0.5, n = 45). On examining the breast tumours, alpha-JSB-1 showed a positive association with c-erbB-2 (P = 0.003), c-myc (P = 0.0004) and c-jun (P = 0.02) but not ER or EGF-R expression. alpha-GSTpi showed a positive association with c-erbB-2 (P = 0.03) and c-myc (P = 0.0004) but not ER, EGF-R or c-jun. Flow cytometric MDR levels were not related to tumour grade or axillary node status. In solid tumours, a relationship between the two antibodies used has been clearly demonstrated, however, specificity of alpha-GSTpi is questioned. Both antibodies show an association with c-erbB-2, which is associated with poor prognosis and with c-myc which is involved in cell cycling and differentiation. Monitoring MDR markers (Pgp) using this methodology may be useful for evaluation of prognosis in breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Heparin administration via nomogram versus a standard approach in venous and arterial thromboembolic disease.

To determine whether heparin administered by continuous intravenous infusion using a nomogram is superior to a random dosing scheme, we performed a prospective, randomized comparative trial in 161 patients. Patients were prospectively randomized to one of three groups. Group I received an intravenous bolus of 5000 IU of heparin followed by heparin administration according to a modification of a previously published nomogram. Group II patients received a 5000 IU intravenous bolus of heparin followed by continuous intravenous heparin infusion with dosage adjustment at the discretion of the treating physician. Group III patients received a continuous intravenous heparin infusion with dosage adjustments at the discretion of the treating physician without the prior administration of a bolus dose. Activated partial thromboplastin time (APTT) was obtained at baseline, 6 h after each heparin dose adjustment and every morning. The mean percent of each patient's APTTs in the subtherapeutic range (< 50 sec) over the course of treatment was 9% for group I and 24% for groups II and III, p = 0.0001. The three groups had a similar percentage of each patient's APTTs within the therapeutic range (50-80 sec). There was a larger percentage of APTTs > 80 sec in group I (46%) compared to group II (31%) or group III (32%), p = 0.01. There were no clinically recurrent deep venous thrombi or arterial thromboemboli in any of the groups. Two patients had documented pulmonary emboli during heparin therapy (one in group I; one in group II). There was no difference in the complication rates of heparin therapy or the need for blood transfusions among the three groups. Patients randomized to the heparin nomogram (group I) achieved an APTT > 50 sec more frequently than patients in the other two groups. Overall, fewer patients in the nomogram group were subtherapeutic, and, when APTT levels fell in the subtherapeutic range, the nomogram restored APTTs to the therapeutic range faster than the standard methods. The heparin nomogram was clearly more effective as a method of heparin dosing than standard methods of anticoagulation dosing.

Aged↗
PubMed1995

Selection of specific phage-display antibodies using libraries derived from chicken immunoglobulin genes.

In chickens, single functional immunoglobulin variable and joining gene segments at each of the heavy and light chain loci undergo V(D)J rearrangement. Diversity is subsequently introduced by conversions templated by upstream pseudo V region genes in such a way that practically all V regions in mature B cells have identical ends. This greatly simplifies the representative amplification of V region genes. Furthermore, the entire naive repertoire of the adult chicken is produced in the bursa of Fabricius of the young bird. These special properties of the generation of immunoglobulin diversity in chickens have been exploited in the development of procedures to produce large libraries of diverse antibody combining sites derived from chicken Ig genes and expressed on filamentous bacteriophage. The utility of this library was assessed by selection of specifically binding phage using three solid phase-bound protein antigens, hen egg white lysozyme, bovine thyroglobulin and bovine serum albumin. The sequences of the V region genes thus isolated demonstrated that selection was specific and that the library contained useful diversity of binding sites. This library provides access to a repertoire whose diversity is based on a mechanism different from that underlying previously available libraries. The demonstrated feasibility of generating chicken phage antibodies may lead to the production of monoclonal reagents from immunised chickens, and the derivation of reagents for studying immunoglobulin mediated selection in avian B cell development.

Amino Acid Sequence↗
PubMed1995

Identification of a novel class of mammalian Fc gamma receptor.

A cDNA encoding an Ig receptor that conferred the ability to bind erythrocytes sensitized with IgG2, but not IgG1, was cloned by screening a cattle alveolar macrophage library, made in the vector pCDM8, expressed in COS-7 cells. A search of the PIR database indicated a greater level of similarity with human Fc alpha R than with any other FcR. The percentage of identical amino acids was 41% and nucleotides 56%. This high similarity is between the extracellular and transmembrane domains; the cytoplasmic tails are unrelated. Similarities with human Fc gamma RI, Fc gamma RII, Fc gamma RIII, Fc epsilon RI, or bovine Fc gamma RII were less than 28%. COS-7 cells transfected with the cloned plasmid bound erythrocytes specifically sensitized with IgG2 but not with IgG1. In tests with heat-aggregated bovine Igs, IgG2 purified from serum bound to transfected COS-7 cells but IgG1 from serum and IgA from tracheobronchial secretions did not. Human serum IgA also failed to bind to transfected COS-7 cells although it did bind to bovine neutrophils and monocytes. Only aggregated bovine IgG2 inhibited the binding of IgG2-sensitized erythrocytes to COS-7 cells transfected with the plasmid. These observations indicate that the FcR bound IgG2 specifically and was not a receptor for IgA. Thus, this receptor, which we have named bovine Fc gamma 2R, represents a novel class of mammalian Fc gamma R, the evolution of which is likely to have been influenced by the truncated hinge of the bovine IgG2 molecule. Analysis of genetic divergence of the genes encoding bovine and human Fc gamma R and Fc alpha R indicated that the novel bovine gene and the human Fc alpha R gene probably evolved from a common ancestor, which is not shared by other Fc gamma R.

Amino Acid Sequence↗
PubMed1995

The utility of duplex ultrasound scanning of the renal arteries for diagnosing significant renal artery stenosis.

OBJECTIVE: To determine the utility of duplex ultrasound scanning of the renal arteries in identifying patients with renal artery stenosis of 60% or more and in excluding patients with either normal renal arteries or renal artery stenosis of less than 60%. DESIGN: A prospective, blinded study. SETTING: Large tertiary referral center. PATIENTS: 102 consecutive patients (44 men and 58 women with a mean age [+@- SD] of 63.3 +/- 13.4 years) who had both duplex ultrasound scanning of the renal arteries and renal arteriography. All patients who were studied had hypertension that was difficult to control, unexplained azotemia, or associated peripheral vascular disease (alone or in combination), giving them a high pretest likelihood of renovascular disease. MAIN OUTCOME MEASUREMENTS: Peak systolic and end diastolic velocities, renal-aortic ratios, resistive index, and kidney sizes. RESULTS: Sixty-two of 63 arteries with stenosis of less than 60% using arteriography were correctly identified by duplex ultrasound scanning. Thirty-one of 32 arteries with 60% to 79% stenosis using arteriography were correctly identified as having 60% to 99% stenosis on duplex ultrasound, whereas 67 of 69 arteries with 80% to 99% stenosis on arteriography were correctly identified as having 60% to 99% stenosis on ultrasound. Twenty-two of 23 arteries with total occlusion on arteriography were correctly identified by duplex ultrasound. The overall sensitivity of duplex ultrasound compared with arteriography was 0.98, the specificity was 0.98, the positive predictive value was 0.99, and the negative predictive value was 0.97. CONCLUSION: Duplex ultrasound scanning of the renal arteries is an ideal screening test because it is noninvasive and can predict the presence or absence of renal artery stenosis with a high degree of accuracy.

Aged↗
PubMed1995

Identification and analysis of the expression of CD8 alpha beta and CD8 alpha alpha isoforms in chickens reveals a major TCR-gamma delta CD8 alpha beta subset of intestinal intraepithelial lymphocytes.

Expression screening has been used to clone cDNAs encoding the alpha- and beta-chains of chicken CD8. Amino acid sequence similarities with the mammalian sequences were about 30%. Many amino acid residues of structural or functional importance were more highly conserved, as were the overall structures of both chains. Like human CD8 alpha, the chicken alpha-chain lacked sites for N-linked glycosylation, but the beta-chain contained three such sites. In COS cells transfected with CD8 beta cDNA, surface expression of the beta-chain was dependent on co-transfection of the alpha-chain cDNA, indicating that, as in mammals, chicken CD8 can be expressed as a CD8 alpha alpha homodimer or as a CD8 alpha beta heterodimer. Immunofluorescence analysis with mAbs that were shown to identify the CD8 alpha- and CD8 beta-chains revealed that the vast majority of the CD8+ cells in the thymus, spleen, and blood of adult chickens express both CD8 alpha- and CD8 beta-chains. However, a relatively large proportion of the CD8+ TCR-gamma delta cells in the spleens of embryos and young chicks express only the alpha-chain of CD8. Among intestinal epithelial lymphocytes the major CD8+ T cell populations present in mice are conserved, but there is a population of TCR-gamma delta CD8 alpha beta cells that is not found in rodents. This observation is important in interpretation of experiments examining the pathways of development of intestinal intraepithelial lymphocytes in chickens.

Amino Acid Sequence↗