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Biomedical subjects

H Alexander

Publications and source records attributed to H Alexander.

At least 145 records · Page 8Linked to original sources

An Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA5) partly encoded by the transformation-associated Bam WYH region of EBV DNA: preferential expression in lymphoblastoid cell lines.

Four peptides were synthesized on the basis of amino acid sequences deduced from a highly spliced transcript encoded by the Bam W, Y, and H fragments of the Epstein-Barr virus (EBV) genome [Bodescot, M., Chambraud, J. B., Farrell, P. J. & Perricaudet, M. (1984) EMBO J. 3, 1913-1917]. Rabbit antisera against three of the four peptides identified a nuclear polypeptide that varied between 22 and 70 kDa in molecular size. Four of 20 EBV-positive human sera contained antibodies against this polypeptide. Since this is the fifth EBV-determined nuclear antigen (EBNA) discovered in growth-transformed cells, it is designated EBNA5. The antigen was detected in virus nonproducer lines (less than 0.01% EBV early antigen expression) and is thus not dependent on the viral cycle. It was differentially expressed depending on the origin of the lines. All 10 lymphoblastoid cell lines tested expressed EBNA5, but it could not be detected in 10 of 11 EBV-carrying Burkitt lymphoma lines. Infection of tonsillar lymphocytes with the B95-8 strain of EBV induced six EBNA5-specific polypeptides that varied between 41 and 70 kDa in molecular size with regular increments of 6 kDa. This may be due to the fact that the EBNA5 coding sequence includes the Bam W internal repeat. Parallel infection of the EBV-negative Burkitt lymphoma line Ramos with the same viral substrain did not induce detectable levels of EBNA5, nor was this antigen present in permanently EBV-converted Ramos sublines. These findings imply that the expression of the viral genome varies among B cells having different phenotypes.

Antibodies, Viral↗

Ligament and tendon repair with an absorbable polymer-coated carbon fiber stent.

Ribbon-like composite structures of filamentous carbon fiber and absorbable polymers have been used in the repair and replacement of both tendons and ligaments. The composite acts as a scaffold upon which new collagenous tissue can grow and has proved successful in a variety of animal models. The results of the first three years of human clinical trials have revealed ingrowth potential similar to that seen in the animal studies. Most patients have shown significant improvement, with many demonstrating good to excellent stability and function.

Animals↗

Antibodies to peptides detect new hepatitis B antigen: serological correlation with hepatocellular carcinoma.

The expression of a previously unidentified gene product, encoded by the hepatitis B virus (HBV) genome, has been achieved with a recombinant SV40 expression vector. Antibodies against synthetic peptides representing defined regions of this protein were used to screen cells infected with recombinant virus as well as tissues naturally infected with HBV. A 24,000-dalton protein (p24) was detected in cells infected with recombinant virus and a 28,000-dalton protein (p28) was detected in tissues infected with HBV. The peptides or recombinant-derived protein were used as antigens to screen sera from individuals infected with HBV. Specific antibodies were detected predominantly in sera from patients with hepatocellular carcinoma. The presence of p28 in tissues infected with HBV and the appearance of specific antibodies in infectious sera establish the existence of an additional marker for HBV infection.

Animals↗

Antibodies against synthetic peptides react with the second Epstein-Barr virus-associated nuclear antigen.

Five peptides were synthesized on the basis of amino acid sequences predicted from the transformation-associated BamHI WYH region of the genome of the Epstein-Barr virus (EBV). Antisera to two peptides deduced from a 1.6-kb open reading frame in the BamHI H fragment identified an 87 000-dalton nuclear polypeptide that was present in EBV-carrying cell lines that expressed the second EBV-determined nuclear antigen (EBNA-2). This polypeptide was not detected in cell lines that carried EBV variants with a deleted BamHI WYH region or in EBV-negative cell lines. Three peptides deduced from the 1.6-kb open reading frame reacted with human EBNA-positive sera, but not with EBNA-negative sera. Following affinity purification with the peptides, two of the corresponding human antibodies also reacted with the 87 000-dalton polypeptide.

Amino Acid Sequence↗

Evaluation of H2O2 prophylaxis of bacteriuria in patients with long-term indwelling Foley catheters: a randomized controlled study.

Since the long-term catheterized patient is at significant risk of urinary tract infection, and the catheter drainage bags of these patients are at significant risk of becoming reservoirs for nosocomial pathogens, we carried out a randomized, controlled study to determine the efficacy of intermittent drainage bag instillation of hydrogen peroxide (H2O2) in patients requiring indwelling Foley catheters for 5 days or more. Herein we report the effects of this technique on the rates of catheter and bag bacteriuria, the duration to positive culture, the temporal relationships observed, and the spectrum of organisms recovered. Bag source bacteriuria was found with the same frequency in both control and H2O2 groups. H2O2 did reduce contamination of the drainage bag but did not reduce catheter-associated bacteriuria or frequency of symptomatic urinary tract infection. Furthermore, H2O2 did not reduce the frequency of bag contamination with most of the common nosocomial urinary pathogens.

Antisepsis↗

Neutral steroid metabolites in patients with uraemia and after renal transplantation: a quantitative and qualitative study in body fluids.

Steroid metabolites enriched from urine, haemofiltrate, and CAPD-dialysate (Continuous Ambulatory Peritoneal Dialysis) were identified by gas chromatography-mass spectrometry and quantified by capillary gas chromatography. The study included twenty healthy controls, twenty-six non-dialysed uraemics, thirty-nine patients on regular dialysis treatment, and twenty-two allograft recipients. Compared to the 24 h urinary excretion rates of controls the excretion rates of androsterone and etiocholanolone were in the lower normal range up to significantly decreased in the body fluids of all patients, and those of the corticoid metabolites were also significantly decreased. 11-Oxygenated androstanolones in urine from non-dialysed uraemics correlated significantly decreased. 11-oxygenated androstano-levels and were significantly increased, but normal in haemofiltrate and CAPD-dialysate, while in urine of allograft recipients the values were significantly lower.

Adrenal Cortex Hormones↗

Thiopental after brain ischemia in monkeys. Cardiovascular and electroencephalographic effects.

The cardiovascular and electroencephalographic (EEG) effects of thiopental were investigated, with and without preceding global brain ischemia (GBI). Four groups of pigtailed monkeys were used: Group I received thiopental 90 mg/kg over 1 h after 16 min GBI. Group II received thiopental 90 mg/kg over 1 h without preceding brain ischemia. Group III received 90 mg/kg over 1, 3, 6, or 8 h with varying infusion rates and no brain ischemia. Group IV, after 16 min GBI, received thiopental 90 mg/kg over 12 h with a gradually reduced infusion rate, keeping thiopental serum levels around 120-140 mumol X l-1 throughout the infusion. Large doses of thiopental (Group II) produced serious cardiovascular side-effects. With co-existing brain ischemia (Group I), these side-effects were much worse; five of six animals not receiving lidocaine prophylaxis suffered circulatory arrest. A prolongation of the Q-T interval on the electrocardiogram may be of pathogenetic importance. In contrast, lower thiopental blood levels, sufficient to depress the EEG to burst suppression or isoelectricity, were well tolerated with and without preceding brain ischemia (Groups IV and III).

Animals↗

Carbon fiber debris within the synovial joint. A time-dependent mechanical and histologic study.

The consequences of release of carbon debris within the synovial joint are of interest to surgeons contemplating the intra-articular repair of cruciate-deficient knees with a carbon fiber-based material. Coverage of carbon fiber implants with absorbable polymer as well as autogeneic graft material has resulted in surgical procedures that minimize potential fiber release. However, finite risk of release of fiber debris certainly exists. With this in mind, a controlled animal experiment to model debris release in the synovial joint was performed. As a positive control, magnesium tetrasilicate (talc) in suspension was injected into the knees of rabbits. Talc produced a transient synovitis severe enough to alter the mechanical properties of the joint cartilage. Carbon fiber debris, when similarly injected, also produced a synovitis. However, the synovitis induced by carbon particulate was not of sufficient severity or duration to alter the mechanical properties of the cartilage. Neither talc nor carbon fiber debris appeared to physically abrade cartilage.

Animals↗

Ligament replacement with an absorbable copolymer carbon fiber scaffold--early clinical experience.

Eighty-two patients, average age 29 years, were surgically treated (during the period from April 1981 to July 1983) for both acute (8%) and chronic (92%) knee ligament instabilities. An absorbable copolymer-carbon fiber ligament prosthesis was used as a tissue scaffold. Seventy-five percent had anterior cruciate ligament reconstructions, 6% had anterior cruciate and posterior cruciate ligament reconstructions, 6% had just posterior cruciate ligament reconstructions, and 9% had other combinations of anterior cruciate ligament, medical collateral ligament, and lateral collateral ligament reconstructions. Preoperative and postoperative evaluation, consisting of questionnaires, physical examinations, and isoskinetic testing, revealed significant improvements in categories of stability, pain, function, and strength persisting to the end of the study at 24 months. Arthroscopic examination and histologic studies of retrieved specimens demonstrated well-vascularized reconstructions with collagenous tissue ingrowth into the carbon-copolymer implants.

Adolescent↗

The electrical stimulation of bone using a filamentous carbon cathode.

Filamentous carbon fiber is an extremely compatible biomaterial. It does not corrode and elicits almost no foreign body response. In addition, this material is an efficient electrical conductor in vivo. These desirable characteristics suggest that carbon fiber may be of use as an electrode material for the stimulation of bone and/or soft tissue growth. This possibility has been investigated in a well established laboratory animal model. When used as a cathode material in conjunction with an implantable constant direct current device, carbon fiber was shown to be an effective electrode material for the stimulation of bone and fibrous tissue within the medullary canal of the tibia of the rabbit. Further, adjustment of current levels appear to allow some selectivity in terms of the amount and type of tissue produced. Currents in the 1 microA range produced a maximum amount of bone, whereas a 20 microA current produced a maximum amount of fibrous tissue. Intermediate current levels produced a proportional mix of bone and soft tissue.

Animals↗

Antibodies against a synthetic peptide identify the Epstein-Barr virus-determined nuclear antigen.

Five peptides corresponding to amino acid sequences predicted from all three reading frames of the nucleotide sequence of the third internal repeat array (IR3) of the Epstein-Barr virus (EBV) genome were synthesized chemically. All five peptides elicited antipeptide antibodies in rabbits. The antiserum raised against a 14-residue copolymer of glycine and alanine gave brilliant EBV-specific nuclear staining in the anticomplement immunofluorescence (ACIF) assay, in line with the original definition of the EBV-determined nuclear antigen (EBNA) [Reedman, B. M. & Klein, G. (1973) Int. J. Cancer 11, 499-520]. Eight EBNA and EBV DNA-carrying lines showed nuclear staining with the antipeptide antibody, whereas five EBV DNA negative lines failed to stain. The staining pattern was more discretely punctate than the finely dispersed diffuse EBNA staining obtained with human antisera. Human EBV antibody-positive but not EBV-negative sera reacted with the synthetic peptide in an ELISA test. The peptide-specific antibodies were purified from the sera of healthy EBV-seropositive persons by affinity chromatography with the peptide. They gave an EBV-specific, brilliant punctate nuclear ACIF staining similar to that of the rabbit antipeptide antibodies. It was concluded that the glycine-alanine structure encoded by the IR3 region contains a native determinant of EBNA, detected by the ACIF test. Immunoblotting with the rabbit and human peptide-specific antibodies identified poly-peptides that varied between 70 and 92 kilodaltons in size in different EBV-positive cell lines, corresponding closely to a previously identified variation pattern in the size of EBNA. In addition, rabbit antipeptide antibodies identified two cellular polypeptides, 44 and 49 kilodaltons in size.

Amino Acid Sequence↗

Thiopental treatment after global brain ischemia in pigtailed monkeys.

The authors investigated the value of high-dose thiopental (TH) therapy after 16-min complete global brain ischemia (GBI) in three groups of pigtailed monkeys, using a neck cuff model of GBI with 96 h intensive care postischemia (PI). Control group (n18): Normotension was restored within 2 min PI; paralysis/controlled ventilation was maintained for 48 h PI with 50% N2O/O2. Thiopental loading group (n13): Control treatment plus TH-loading with 90 mg/kg iv given from 5 to 65 min PI (mean peak TH plasma level 130 micrograms/ml). Thiopental anesthesia group (n14): Control treatment plus TH anesthesia with 90 mg/kg iv given over 12 h PI (sustained TH plasma levels of 25-35 micrograms/ml and EEG burst suppression). Norepinephrine requirement for blood pressure control PI was greater in the TH groups than in the control group (P less than 0.05). Lidocaine was needed for control of arrhythmias in the TH loading group. There was no significant difference in mortality or neurologic outcome between the groups. At 96 h PI seven of 11 animals were awake in the control group, compared with seven of 12 and six of 12 in the two TH groups. Neurologic deficit scores (NDS) for the survivors at 96 h PI were 23 +/- 6% (mean +/- SD) (n10) in the control group, compared with 25 +/- 9% (n11) and 26 +/- 12% (n10) in the two TH groups (NDS 100% = brain death, 0% = normal). Seizures PI (in 1-2 of each group) were associated with worse neurologic deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prolonged immobilization and controlled ventilation do not improve outcome after global brain ischemia in monkeys.

This study is a therapeutic evaluation of prolonged immobilization and controlled intermittent positive-pressure ventilation (IPPV) after global brain ischemia (GBI) in pigtailed monkeys. Sixteen min of GBI was produced with a high-pressure neck cuff, while the lungs were being continuously ventilated. Normotension was restored within 2 min postischemia (PI). The control group of 13 monkeys was weaned from IPPV 4 to 6 h PI. The treatment group of 18 animals was paralyzed and ventilated with a 50:50 nitrous oxide-oxygen mixture for 48 h PI. Intensive care was maintained for 96 h PI. In the control group, 8 of 10 animals were awake at 96 h PI compared to 7 of 11 in the treatment group. Neurologic deficit scores for the survivors in the 2 groups were also not significantly different. Histologic examination supported this conclusion. Paralysis/IPPV for 48 h post-GBI with 50% N2O facilitates control of blood gases and blood pressure, but does not improve the neurologic outcome over that achieved with only 4 to 6 h controlled ventilation.

Animals↗

Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs.

Calcium entry blockers can ameliorate postischemic cerebral hypoperfusion, protect the myocardium against ischemia, and may protect against early postischemic neurologic deficit. This study documents that a calcium entry blocker, given after cardiac arrest, can ameliorate late postischemic neurologic deficit (ND). Thirty-four dogs received 10 min of ventricular fibrillation, restoration of spontaneous circulation by external cardiopulmonary resuscitation, and standard postarrest intensive care. Eleven of these dogs were given lidoflazine, 1 mg/kg body weight, within 10 min postarrest and again at 8 h and 16 h. Pupillary light reflexes, EEG activity, arterial-cerebrovenous oxygen gradients (O2 demand/supply ratios) and intracranial pressure were the same in both groups. After weaning from controlled ventilation at 24 h, ND scores improved consistently through the 96-h observation period in the lidoflazine-treated dogs. In the control group, ND scores were significantly higher than in the lidoflazine-treated dogs. In the lidoflazine-treated group, 5/11 dogs achieved normal overall performance and none remained comatose, whereas all control dogs had some deficit and 4/11 remained comatose. Delayed neurologic deterioration occurred in 6/11 control and 0/11 lidoflazine-treated dogs. Total mean cerebral histopathologic damage (HD) scores at 96 h were not significantly different between the two groups; however, individual HD scores and maximum cerebro-spinal fluid (brain-specific) creatine-phosphokinase activity--which increases after brain insults--correlated well with 96-h ND scores. In the lidoflazine group, life-threatening dysrhythmias were less frequent and the norepinephrine requirement for blood pressure maintenance was the same as in the control group. Cardiac output remained at prearrest levels in the lidoflazine-treated dogs, but decreased in the control group, particularly during the first 4 h postarrest.

Animals↗

Quantitative assessment of back strength using isokinetic testing.

The overall objective of this research is to relate disorders of the lumbar spine to the mechanics of the system. An isokinetic-isometric testing procedure was designed, and groups of normal subjects and patients with back pain were tested. The procedure allows sensitive detection of muscle weakness specific to some part of the range of motion or some functional contraction speed. A biomechanical analysis was performed on several parameters of back strength assessment to develop performance indexes that can be used in establishing screening modalities. Maximum torque and trunk angles are different in normal and patient populations.

Adolescent↗

Prevention of postlaminectomy scar formation.

An animal experimental study was performed to investigate prevention of scar formation under lumbar laminectomy by using new biodegradable interposing materials-- polylactic acid (PLA) foam and membrane. The experimental animals consisted of 32 dogs, 16 control and 16 experimental. The experimental surgery consisted of L5 or L6 complete laminectomy and covering of the laminectomy defect with the experimental materials. The same procedure but without the covering of the laminectomy defect was performed on the control group animals. Animals were sacrificed at varying intervals (2-52 weeks) and the lumbar spines were evaluated with histologic preparations. The PLA membrane is found to be a promising material for prevention of scar tissue extension and adhesion after laminectomy but has a problem of marginal fitting. PLA foam is found to behave as a scaffold for scar tissue extension and adhesion onto the nerve. Other foamy materials such as gelatin foam or avitane are probably behaving similarly, causing scar tissue extension and adhesion. The new materials were found to be completely biocompatible and slowly biodegradable. A combined use of posteriorly convexed stiff PLA membrane and marginal gap filler with PLA foam may provide solutions for both prevention of scar tissue extension and adhesion and prevention of postlaminectomy spinal stenosis.

Animals↗