Hospitals can tally the benefits of contract management services.
Explore the source record for details and available documents.
Contract Services↗
Biomedical subjects
L Anderson
Publications and source records attributed to L Anderson.
Efficacy of local graft irradiation in preventing cadaveric renal transplant rejection: a prospective randomized trial.
Successful renal transplantation depends on the modification of the normal immunologic response. The earliest attempts at such modification involved the use of ionizing irradiation. The significant morbidity and mortality of total body irradiation led to its abandonment in favor of the safer technique of local graft irradiation. While still commonly used, the efficacy of this technique has never been evaluated in a prospective, randomized fashion. The present study is a prospective, randomized, double blinded evaluation of the efficacy of the addition of local graft irradiation to our immunosuppressive protocol. One hundred consecutive cadaveric renal transplants were randomized to receive either conventional immunosuppression alone or conventional immunosuppression plus local graft irradiation delivered in doses of 150 rads on the 1st, 3rd and 5th post-operative days. Patients were followed for a period of 2 years. No significant difference was demonstrated between the groups among any measured parameter. In conclusion, the addition of local graft irradiation in doses of 150 rads on d 1, 3, and 5 does not appear to offer any advantage over standard immunosuppressive therapy and its use cannot be recommended.
Adult↗
The genetic defect in multiple endocrine neoplasia type 2A maps next to the centromere of chromosome 10.
Multiple endocrine neoplasia type 2A (MEN2A) is a rare cancer syndrome that is inherited in an apparently autosomal dominant fashion. Previous linkage studies had assigned the MEN2A locus to chromosome 10 in the pericentromeric region. We recently have described several new easily scorable RFLPs for the chromosome 10-specific alpha satellite DNA (the D10Z1) locus that is known, on the basis of previous in situ hybridization experiments, to lie at the centromere. We report here tight linkage between MEN2A and D10Z1, as demonstrated by a maximum lod score of 12.02 at the recombination frequency of zero (1-lod-unit support interval 0-4 cM), indicating that the genetic defect in MEN2A lies in the immediate vicinity of the centromere. By means of a set of ordered polymorphic DNA markers from the pericentromeric region, multipoint as well as pairwise linkage analyses place the MEN2A locus at the middle of a small region (approximately 11 cM) bracketing the centromere with FNRB (at 10p11.2) and RBP3 (at 10q11.2) on either side, providing further support for the centromeric location of the MEN2A locus. Marked sex difference in recombination frequencies exists in this pericentromeric region: significantly (P less than .01) more female than male crossovers were observed across all of the adjacent intervals D10S24-FNRB, FNRB-D10Z1, and D10Z1-RBP3. However, a sex difference was not seen in the 7-cM interval from RBP3 to D10S5, suggesting that large variation in the sex difference in recombination can occur over small chromosomal regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Centromere↗
The beta subunit locus of the human fibronectin receptor: DNA restriction fragment length polymorphism and linkage mapping studies.
The beta subunit of the human fibronectin receptor (FNRB) is a transmembrane protein belonging to the VLA (very late antigens of activation) family. Using pGEM-32, a 2.5-kb partial cDNA clone corresponding to the 3' portion of the human FNRB locus, multiple restriction fragment length polymorphisms (RFLPs) were revealed on DNAs from unrelated Caucasians. RFLPs detected by five enzymes, BanII, HinfI, KpnI, BglII, and SacI, are of the simple two-allele form, and pairwise linkage analyses of these RFLPs with numerous known DNA markers from the chromosome-10 pericentromeric region not only confirmed the chromosome-10 assignment of the functional FNRB gene but also supported its localization at p11.2 suggested by in situ hybridization. An infrequent MspI RFLP was detected by pB/R2, a 4.6-kb genomic clone from the FNRB locus. Another type of DNA polymorphism was also revealed by the cDNA clone and it was visualized on the Southern blot analyses as the presence or absence of an extra band (or a set of extra bands). It seems to stem from a stretch of DNA sequence present in some individuals at one single locus but absent in others, and is of non-chromosome-10 origin based on linkage analyses with known chromosome 10 markers. This "presence/absence" type of polymorphism could be revealed by all of the 25 restriction enzymes tested and is similar in nature to that previously reported with one of the human dihydrofolate reductase pseudogenes, DHFRP1. Dissection of the pGEM-32 clone demonstrated that the region revealing the non-chromosome-10 sequences is within a fragment about 1.7 kb in length extending from about 600 nucleotides preceding the stop codon down to the end of the cloned FNRB 3' untranslated region. Due to its high polymorphism information content (PIC) value (0.71 for haplotypes of BanII, HinfI, and KpnI RFLPs) and proximity to the centromere. FNRB will prove to be a highly useful marker for genetic linkage studies of multiple endocrine neoplasia type 2A (MEN2A) as well as for chromosome-10 linkage studies in general.
Chromosome Mapping↗
Thrombolysis and Angioplasty in Myocardial Infarction (TAMI-1) trial: influence of infarct location on arterial patency, left ventricular function and mortality.
The influence of infarct location on arterial patency, left ventricular function and mortality after 150 mg of intravenous recombinant tissue-type plasminogen activator (rt-PA) and selective coronary angioplasty was studied in 386 patients with acute myocardial infarction. In 329 patients with acute and 1 week angiograms, the 90 min infarct-related artery patency rate after rt-PA in the left anterior descending, the left circumflex and the right coronary artery was 77, 68 and 68%, respectively. Angioplasty, performed in half the patients, resulted in a final acute patency rate of 93%, which was not related to arterial distribution. Repeat catheterization and revascularization were required in 12% of patients before day 7 and were independent of arterial distribution. The reocclusion rate for the right coronary artery (21%) was higher than that for the left anterior descending (12%) or left circumflex (5%) artery (p = 0.01). Acute and 1 week contrast ventriculograms suitable for analysis were available in 266 patients. Whereas serial left ventricular ejection fraction did not improve during the course of this study, serial regional wall motion (centerline chord method) improved in each arterial distribution. The in-hospital mortality rate of 6% was not related to arterial distribution, although death was twice as likely with proximal compared with distal lesions. Ten of 11 patients who died in the group with the left anterior descending artery as the infarct-related artery had a lesion proximal to the first septal perforator branch.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Pharmacodynamics of thrombolysis with recombinant tissue-type plasminogen activator. Correlation with characteristics of and clinical outcomes in patients with acute myocardial infarction. The TAMI Study Group.
Coagulation analysis was performed on blood samples from 386 patients with acute myocardial infarction drawn before, during, and after a continuous intravenous infusion of 150 mg recombinant tissue-type plasminogen activator (rt-PA) (Activase). Plasma rt-PA rose to peak levels of 2.1 +/- 3.1 micrograms/ml (mean +/- SD). Fibrinogen levels measured by coagulation rate and by sulfite precipitation decreased from baseline levels of 3.0 +/- 0.9 and 3.2 +/- 1.0 g/l, respectively, to nadir levels of 1.4 +/- 0.75 and 1.8 +/- 0.92 g/l, respectively, and were associated with peak levels in serum of fibrinogen-degradation products (FDP) of 230 +/- 470 micrograms/ml. Forty percent of patients experienced a nadir functional-fibrinogen level of less than 1.0 g/l, whereas 20% fell below 0.5 g/l. Nadir fibrinogen levels did not correlate with patency of the infarct-related coronary artery at 90 minutes or with risk of coronary vessel reocclusion within 7-10 days. However, the risk of coronary artery reocclusion was inversely related to the baseline functional fibrinogen level (p = 0.0008), with the magnitude of its drop to nadir level (p = 0.0003) as well as to peak levels of FDP (p = 0.038). Quantitative blood loss correlated with all markers for systemic fibrinogenolysis including nadir fibrinogen level (r = -0.20, p = 0.0011), percent decrease of fibrinogen (r = 0.22, p = 0.001), and peak FDP levels (r = 0.14, p = 0.020). Both patients who experienced intracranial hemorrhage presented with high baseline fibrinogen levels and experienced extensive degradation of coagulable fibrinogen. Overall, patients at greatest risk of systemic fibrinogenolysis tended to be relatively older women with lower body weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Coagulation↗
Clinical enhancement of post-periodontal surgical therapy by a 0.12% chlorhexidine gluconate mouthrinse.
Previous studies have demonstrated the potential beneficial effects of post-surgical rinsing with 0.2% chlorhexidine. In the present investigation a new chlorhexidine formulation (Peridex) (CHx) and concentration (0.12%) was evaluated clinically to determine if similar effects could be detected from the use of the new product and treatment regimen. A double blind, randomized, placebo-controlled study was carried out in 40 patients during a 6 week period. Patients who had moderate periodontitis (AAP Class III) received osseous periodontal surgery in one quadrant. Each surgical site received periodontal dressing and patients were given a placebo or CHx mouthrinse to be used twice each day. Compared to placebo, CHx significantly reduced plaque at all examinations (54.4% reduction over placebo at 6 weeks, P less than 0.05). Visible plaque (PlI greater than 2) in the CHx group was reduced by 99% over the placebo group at 6 weeks and at 4 weeks post-surgical, gingival inflammation scores were significantly lower in the CHx group (17% reduction over the placebo at 4 weeks, P less than 0.05). Gingival bleeding scores (GI greater than 2) were significantly lower in the CHx group at 4 and 6 weeks (41% and 40% reduction over the placebo group, P less than 0.05). Probing pocket depth and attachment level changes were not significantly different between both groups. Epithelialization rates and pain assessment demonstrated consistently better results in the CHx group, although differences were not statistically significant. Use of 0.12% chlorhexidine immediately following periodontal surgery, for 6 weeks, has been shown to be a clinically effective adjunct providing enhancement of the post-surgical management of periodontal surgical patients.
Chlorhexidine↗
Effect of 0.12% chlorhexidine on bacterial recolonization following periodontal surgery.
Bacterial plaque accumulation following periodontal surgery has been directly associated with delayed and altered surgical wound healing. Successful antimicrobial treatment following periodontal surgery depends upon the elimination and suppression of wound associated microorganisms. Highly effective antimicrobials should also prevent recolonization of periodontopathogens. In this investigation, the antimicrobial effect of a 0.12% chlorhexidine gluconate mouthrinse (Peridex) on bacterial recolonization after periodontal surgery was determined. A double-blind, randomized, placebo-controlled study was carried out on 40 patients for 6 weeks. Patients with moderate periodontitis (AAP Class III) underwent osseous periodontal flap surgery in one quadrant. Subgingival and marginal plaque samples from the surgery area were taken prior to surgery and 2 and 6 weeks postoperatively. General descriptive bacteriological cultural analysis and assays for specific microbial populations were carried out. During the 6 weeks of mouthrinse use, patients using chlorhexidine had significant reductions over placebo (P less than 0.05) in the number of total Gram-positive facultative cocci, streptococci (85.8%); Gram-positive facultative rods, primarily Actinomyces (91.7%); Capnocytophaga (97.6%) and Gram-negative anaerobic rods (94.5%). Few black pigmented Bacteroides or Actinobacillus actinomycetemcomitans were found prior to surgery or any time postoperatively. In the chlorhexidine group, 6 weeks post surgery, streptococci were the predominant bacterial group in the sampled plaque. Quantitatively, the distribution of bacteria, after 2 and 6 weeks of mouthrinse use, was consistent with a young, less mature plaque. A previous study demonstrated that this plaque was associated with clinical health.
Adult↗
Replicative cultures of adult human and rhesus monkey liver epithelial cells.
Exploratory experiments indicate that media containing lipids, phosphoethanolamine, epidermal growth factor, insulin, cholera toxin, bovine pituitary extract, chemically denatured serum, and triiodothyronine will support replicative cultures of normal liver epithelial cells obtained from adult Rhesus monkey and human donors. In addition, we have extended the culture population doubling potential of the human liver epithelial cells by their transfection with a plasmid containing the SV40 virus T-antigen gene. The T-antigen gene-containing cells continued to express albumin through 40 population doublings. Finally, results of preliminary experiments suggest that it may be possible to induce human liver epithelial cells to undergo differentiation to hepatocyte-like cells either by injecting them into the spleen of an athymic nude mouse or by incorporating them into a collagen "tissue equivalent" matrix.
Animals↗
Gene mapping of a simulated complex disease.
Explore the source record for details and available documents.
Alleles↗
Cytoadherence by Plasmodium falciparum-infected erythrocytes is correlated with the expression of a family of variable proteins on infected erythrocytes.
Plasmodium falciparum-infected erythrocytes (IRBCs) adhere specifically to venular endothelium and thereby evade spleen-dependent immune mechanisms. We have investigated the molecular basis of cytoadherence. We report here that the capacity for cytoadherence of IRBCs is correlated with the expression of a family of variable proteins on the surface of IRBCs. Essential to these studies was the use of in vitro techniques for modulating the cytoadherence phenotype of cloned parasites. In initial studies, we found culture-adapted parasites to be poorly cytoadherent or noncytoadherent. To select for cytoadherent parasites, we incubated knobbed IRBCs with C32 melanoma cells and cultured the adherent cells. Repeated rounds of selection produced parasites with increased cytoadherence. To select for noncytoadherent parasites, we cultured the cells that did not adhere to C32 melanoma cells. Cytoadherent IRBCs from two different cloned isolates had large (Mr greater than 2.4 x 10(5) radioiodinatable proteins that differed in size between the isolates but had in common the biochemical properties of trypsin sensitivity and insolubility with Triton X-100. The proteins were not detected with uninfected erythrocytes, indicating that they were parasite determined, nor were they detected with IRBCs containing parasites cultured for many months without selection. With continued selection for the cytoadherent phenotype, additional IRBC surface proteins with larger molecular sizes (Mr 2.9 x 10(5) and 3.2 x 10(5] appeared. A sequence of reversible changes in the cytoadherence phenotype of cloned parasites was accompanied by variation in the molecular size of the IRBC surface protein. Increased cytoadherence was correlated with expression of larger proteins and decreased cytoadherence was correlated with expression of smaller proteins; there was no change in the molecular size of two other parasite proteins associated with the IRBC membrane. The results indicate that the expression of this family of proteins is closely linked to the cytoadherence phenotype of the parasites, suggesting that the members of the protein family have a role in mediating cytoadherence between IRBCs and endothelial cells.
Animals↗
Human retrovirus family: cancer, central nervous system disease, and AIDS.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
A convenient synthesis of 4-amino-4-deoxy-L-arabinose and its reduction product, 1,4-dideoxy-1,4-imino-L-arabinitol.
Methyl beta-D-xylopyranoside in a mixture of N,N-dimethylformamide and 2-methoxypropene containing a little hydrogen chloride gave preponderantly the 2,3-O-isopropylidene derivative, which was readily converted into its 4-trifluoromethanesulfonate. The facile displacement of the triflate group gave a 4-azido-4-deoxy-alpha-L-arabinopyranoside derivative, and this, on mild acid treatment, was hydrolyzed to the 2,3-diol, or under more vigorous conditions to 4-azido-4-deoxy-L-arabinose. Methyl 2,3-di-O-acetyl-4-azido-4-deoxy-alpha-L-arabinopyranoside, from the diol, appears (1H-n.m.r. data) to exist as an equilibrating mixture of the 4C1 and 1C4 conformers in chloroform solution. The reduction of the azido sugar by hydrogen over Pd/C in .6M HCl yielded 4-amino-4-deoxy-L-arabinopyranose as its hydrochloride; in 0.1M HCl, further reactions occurred to give 1,4-dideoxy-1,4-imino-L-arabinitol as the final product. The aminodeoxypentose from lipid A precursor IIA, isolated from a Salmonella mutant by Raetz et al. in 1985, was shown to be identical with the synthetic aminoarabinose by t.l.c., 1H-n.m.r. spectroscopy, and g.l.c. of the acetylated reduction products.
Amino Sugars↗
Synthesis of a close analog of the repeating unit of the antifreeze glycoproteins of polar fish.
The protected glycopeptide N-(benzyloxycarbonyl)-L-alanyl-[O-(2,3,4,6-tetra-O-benzoyl-beta-D- galactopyranosyl)-(1----3)-O-(2,4,6-tri-O-benzyl-alpha-D-galactopyranosy l)- (1----3)]-L-threonyl-L-alanine 2,2,2-trichloroethyl ester was made by coupling the respective disaccharide and tripeptide blocks. The disaccharide block was generated by coupling tetra-O-benzoyl-alpha-D-galactopyranosyl bromide to allyl 2,4,6-tri-O-benzyl-alpha-D-galactopyranoside and converting the product into O-(2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl)-(1----3)-2,4,6-tri-O -benzyl - alpha-D-galactopyranosyl chloride via the 1-propenyl glycoside and the free (1-OH) sugar. Alternatively, the 1-propenyl intermediate was obtained directly by using 1-propenyl 2,4,6-tri-O-benzyl-alpha-D-galactopyranoside as the acceptor in the initial coupling reaction. An efficient 3-step synthesis of 10 was accomplished by the dibutyltin oxide-assisted, selective crotylation of allyl alpha-D-galactopyranoside at O-3, followed by benzylation and treatment of the product with potassium tert-butoxide. The N-benzyloxycarbonyl (Z) and N-tert-butoxycarbonyl (Boc) 2,2,2-trichloroethyl esters of Thr-Ala and Ala-Thr-Ala were formed by sequential coupling. The silver triflate-promoted glycosylation of the Z-protected dipeptide and tripeptide by 2,3,4,6-tetra-O-benzyl-alpha-D-galactopyranosyl chloride, and of the tripeptide by 6, proceeded with excellent alpha-stereoselectivity. From the disaccharide tripeptide 21, the carboxyl-deprotected and fully deprotected derivatives were prepared.
Animals↗
The cholecystokinin antagonist L-364,718 inhibits the action of cholecystokinin but not bombesin on rat pancreatic secretion in vivo.
The action of an antagonist of peripheral CCK receptors, L-364,718 on CCK8 and bombesin-induced pancreatic exocrine secretion was studied in anaesthetized rats. Both CCK8 and bombesin increased the rate of flow and rate of enzyme secretion from the pancreas. Intravenous L-364,718 inhibited the actions of CCK8, but not those of bombesin. It is concluded that bombesin acts on the exocrine pancreas directly rather than through the release of CCK.
Animals↗
Congenital abnormalities in two sibs exposed to valproic acid in utero.
Neural tube, craniofacial, and other congenital abnormalities have been described in infants born to mothers with epilepsy who were treated with valproic acid (VPA) during pregnancy. The pathogenetic relationship between the congenital abnormalities and exposure to VPA is not clear. We describe 3 sibs born to a mother with epilepsy. Only the 2 sibs who were exposed to VPA in utero had certain of the characteristic craniofacial changes described in previous reports of children with similar exposure. In addition, the 2 affected children had other craniofacial and skeletal abnormalities which have not been reported previously as teratogenic sequelae of VPA exposure. Many of the minor anomalies present in the 2 affected patients resemble those observed in rhesus monkeys exposed to VPA in utero. This suggests that the abnormalities observed in the 2 children may have been a consequence of intrauterine exposure to VPA.
Abnormalities, Drug-Induced↗
Hepatocellular carcinoma in a child with familial Russell-Silver syndrome.
We describe a 4-year-old boy with Russell-Silver syndrome (RSS) found to have hepatocellular carcinoma. The brother of this child also had manifestations of RSS. This is the third malignancy and the first hepatocellular carcinoma described in a patient with RSS. The coexistence of hepatocellular carcinoma and RSS may be completely fortuitous; however, the known association of liver cancer with growth abnormality and hemihypertrophy, findings also present in RSS, suggest that these disorders may be related.
Abnormalities, Multiple↗
Infants of azotemic mothers: a report of three live births.
Women with severe renal failure rarely conceive, and when they do become pregnant these women often deliver prematurely. The clinical course of mothers with renal failure has been described, but little attention has been given to the offspring. In this report, we provide data on three infants born prematurely to mothers either on dialysis or with severe renal failure. The infants were the appropriate size for gestational age and demonstrated no obvious physical abnormalities. Laboratory data, including renal function, was also within normal limits. Renal size in the two infants studied by ultrasound was near or above the 95th percentile when corrected for gestational age. The premature birth appeared to be a function of maternal complications rather than a primary in utero growth disturbance.
Adolescent↗