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Biomedical subjects

J Anderson

Publications and source records attributed to J Anderson.

At least 361 records · Page 20Linked to original sources

Adhesion co-receptor expression and intracellular signalling in HIV disease: implications for immunotherapy.

OBJECTIVES: To investigate, in lymphocytes from HIV-1-infected individuals, the phenotypic expression of various adhesion co- or counter-receptors [lymphocyte function-associated antigen (LFA)-3, LFA-1 and intercellular adhesion molecule (ICAM)-1] involved in providing the co-stimulatory signal through the phospholipase C-gamma pathway in relation to inositol polyphosphate metabolism. DESIGN AND METHODS: Cell adhesion molecule profiles of peripheral blood lymphocytes (PBL) from 39 HIV-1-infected individuals at various stages of infection and 20 healthy laboratory controls were studied using flow cytometry. These were studied in 14 patients with late-stage disease in conjunction with their inositol polyphosphate metabolic profiles measured by high performance liquid chromatography. Levels of HIV-1 present in cell lysates were concurrently measured by a p24 antigen capture assay. In addition, the effects of a specific anti-ICAM-1 antisense oligonucleotide on the intracellular phosphatase activities of lymphocytes from a separate group of eight HIV-1-infected individuals were examined. RESULTS: The expression of LFA-1, a beta 2 integrin, was upregulated among patient PBL in parallel with disease progression, whereas that of LFA-3 (CD58) was found to be significantly reduced among the CD4+ lymphocyte subset in all stages of infection. The 5-phosphatase activity, which we previously observed to be defective in HIV disease, was found to correlate linearly with the expression of both LFA-1 and its ligand, ICAM-1. Treatment of patient lymphocytes with an antisense oligonucleotide, which reduced the cell surface expression of ICAM-1 by blocking the translation of its mRNA, resulted in further reduction of intracellular phosphatase activities. CONCLUSIONS: Our results suggest a pivotal role for adhesion co- and counter-receptors in influencing lymphocyte signalling and hence cellular response to recall antigens in HIV-1-infected individuals.

Antigens, CD↗

Hydroxyapatite-coated hip prostheses. Early results from an international study.

A hydroxyapatite-coated hip prosthesis designed to stimulate proximal femoral stress transfer was studied in 222 patients undergoing primary total hip arthroplasty with a minimum followup of 2 years. The femoral component was a roughened titanium alloy with a 50-mu coating of hydroxyapatite applied to the proximal third. A proximal press-fit technique was applied with distal femoral over-reaming as standard procedure. The hydroxyapatite-coated acetabulum was of hemispherical design. Analysis of the clinical results showed a mean Merle D'Aubigné score of 16.7 points at 6 months and 17.4 points at 2 years. Mild residual thigh pain of unknown origin was reported in 3.6% of patients at 2 years. Radiographic evaluation showed complete acetabular and proximal femoral osseointegration without any loosening. No radiolucency or reactive line formation was observed around the hydroxyapatite-coated areas of the prostheses. Femoral bone densification occurred at the coated-uncoated transition zone (54%); 4% to 6% of cases showed cortical hypertrophy at the uncoated area of the stem. Reactive lines were seen around the distal stem in 52% of patients after 2 years. The clinical outcome was excellent, and the radiographic data pointed mainly to proximal femoral stress transfer.

Adult↗

The evolution of the implanted pacemaker's window to the world.

An implanted pacemaker can only communicate with the outside world through its window, i.e., the clinical programmer. Since its inception, the pacemaker has evolved from a non-programmable device to a complex device. Therefore, programming a modern implantable pacemaker could be very challenging for non-experienced or infrequent users. Various programmer-based automatic functions have been developed to reduce programming time and complexity and to obtain accurate measurements. With increasing interests in the telecommunications and information exchange, these programmer-based automatic functions are pushing forward a future vision that automatic pacemaker follow-up procedures via telecommunications are possible for patients located in any corner of the globe.

Biomedical Engineering↗

Aspects of fibromyalgia in the general population: sex, pain threshold, and fibromyalgia symptoms.

OBJECTIVE: To investigate relationships between sex, pain threshold and fibromyalgia (FM) symptoms in the general population. METHODS: Data were obtained from a randomized populations survey of 3,006 persons in Wichita, KS and a subsample of 391 who completed a detailed interview and had an examination. Tender point counts, dolorimetry scores, clinical and psychological variables were measured. RESULTS: Dolorimetry scores were 2.04 kg/cm (1.42-2.66) lower in women than men, and women were almost 10 times more likely to have 11 tender points [OR 9.6 (2.00-46.3)] than men. Women are also more likely to have FM symptoms than men: "Pain all over," [OR 3.94 (1.34-11.38)], sleep disturbance [OR 3.06 (1.45-6.46)], fatigue [OR 4.52 (2.03-10.09)], and irritable bowel syndrome [OR 5.23 (1.83-14.96)]. Tender point counts are more correlated with FM symptoms than dolorimetry scores. CONCLUSION: Symptoms of FM are correlated with pain threshold in the general population, but tender point counts correlate better than dolorimetry. These 2 measures of pain threshold assay different but overlapping factors. Pain threshold is lower in women; and women have more FM symptoms. Decreased pain threshold correlates with all of the symptoms of FM, even in those who do not meet criteria for the syndrome. This suggests that decreased pain threshold, as measured by the tender point counts, is an intrinsically important aspect of patient distress, regardless of the extent and kind of concomitant disease; and that much can be learned about patients by employing this examination.

Disability Evaluation↗

Outpatient bone marrow harvest: the Cleveland Clinic experience.

Patients undergoing a bone marrow harvest have traditionally been hospitalized for several days. Recently, the feasibility of outpatient bone marrow harvesting has been reported. We retrospectively examined the results of 485 patients undergoing an outpatient bone marrow harvest from 1989 to 1993. One hundred and eleven patients were normal donors and the remaining patients were undergoing a bone marrow harvest for autologous transplants. Four hundred and eighty one patients (99%) were discharged within 12 h of the harvest and none have developed long-term complications from the procedure. We additionally analyzed harvest yield with respect to time under anesthesia and underlying diagnosis. Surprisingly, time under anesthesia correlated negatively with harvest yield (P = 0.0001). After adjusting for volume harvested and time under anesthesia, harvest yield was higher in normal donors and patients with breast cancer than for patients with non-Hodgkin's lymphoma and Hodgkin's disease. We conclude that outpatient harvesting is safe. The negative correlation of time under anesthesia with harvest yield may be a result of variables which are difficult to quantify, such as bone marrow microenvironment.

Adult↗

Carbonic anhydrase is present in human oesophageal epithelium and submucosal glands.

Carbonic anhydrase (EC 4.2.1.1) activity was investigated in normal human oesophageal mucosa using the Hansson and Ridderstråle catalytic cobalt methods. The enzyme was detected in the cell membranes and nuclei and, to a lesser extent, in the cytoplasm of the epithelial cells of the mucosa giving a 'chicken wire' appearance. Activity decreased towards the lumen. Other stratified squamous epithelia--buccal mucosa, ectocervix and skin--gave a similar pattern. Acinar cells of oesophageal submucosal glands also exhibited activity for the enzyme, but the ducts did not. The formation of reaction product was prevented by acetazolamide and ethoxzolamide and by the omission of bicarbonate frm the substrate medium. Carbonic anhydrase in oesophageal squamous epithelium may be involved in the control of intra- and extracellular pH, while that in the glands is more likely to be concerned with bicarbonate secretion.

Carbonic Anhydrases↗

Marrow transplants from unrelated donors.

Unrelated-donor transplants have been a realistic option for an increasing number of patients, and the results of these transplants are favorable for patients with good prognostic features. Timing of the transplant early in the course of disease, before malignant clones become resistant to therapy and while the patient remains in good clinical condition, is a critical variable. Further improvements in the safety and efficacy of unrelated-donor transplants will require new approaches to GVHD prevention, better supportive care, acceleration of immune reconstitution and facilitation of tolerance induction without loss of the graft-versus-leukemia effect.

Adult↗

Cloning and identification of annexin II as an autocrine/paracrine factor that increases osteoclast formation and bone resorption.

Autocrine products of osteoclasts such as interleukin-6 may play an important role in normal osteoclast formation and activity. To identify novel stimulatory factors for osteoclasts, we have prepared a mammalian cDNA expression library generated from highly purified human osteoclast-like multinucleated cells (MNC) formed in long term bone marrow cultures and screened this library for autocrine factors that enhance MNC formation. A candidate clone which stimulated MNC formation was isolated. Sequence analysis showed that this cDNA encoded annexin II (AXII). Purified recombinant AXII significantly increased MNC formation in human bone marrow cultures in the absence of 1,25-(OH)2 vitamin D3 and enhanced MNC formation in mouse bone marrow cultures treated with 10(-9) M 1,25-(OH)2 vitamin D3. The enhanced MNC formation in murine marrow cultures resulted in increased bone resorption. Treatment of fetal rat long bones with AXII and 1,25-(OH)2 vitamin D3 significantly increased bone resorption compared to 1,25-(OH)2 vitamin D3 alone. Reverse transcriptase polymerase chain reaction analysis demonstrated that AXII mRNA was expressed at high levels in RNA isolated from highly purified giant cells from osteoclastomas, human osteoclast-like MNC, and pagetic bone. Western blot analysis of conditioned media collected from human marrow cultures showed that AXII was present in the media. Furthermore, approximately 50% of total AXII produced by cells transfected with AXII cDNA was present in the conditioned media. These data suggest that the AXII is an autocrine factor that enhances osteoclast formation and bone resorption and demonstrate a previous unknown function for AXII.

Animals↗

Endothelial injury during extracorporeal circulation: neutrophil-endothelium interaction induced by complement activation.

This study was designed to understand the physiologic intravascular and intradevice events at the cellular level following complement system activation during extracorporeal circulation. The addition of anaphylatoxin C5a or complement-activated serum into neutrophil- or endothelial cell-suspensions resulted in a dose-dependent transmembrane stimulation that was assessed by an intracellular free calcium ion mobilization technique using a calcium-sensitive photoprotein, aequorin. The adhesion and ruffle formation of neutrophils on endothelial cell monolayers were markedly enhanced when both cell types were treated with C5a or activated serum. The significance of complement activation on intravascular events during extracorporeal circulation is emphasized and discussed from the viewpoint of surface-expressed adhesion molecules.

Calcium↗

Five novel point mutations: two causing haemophilia B and three causing factor X deficiency.

Factors IX and X are plasma glycoproteins important in the middle phase of the coagulation cascade, and a bleeding disorder of variable severity results from abnormalities in the expression of either gene encoding these proteins. Nearly 380 unique molecular mechanisms cause factor IX deficiency, or haemophilia B, but only a limited number of mutations causing congenital factor X deficiency have been characterized to date. In this study enzymatic amplification has been used to examine the molecular basis for factor IX deficiency in two patients and factor X deficiency in two patients. Genomic DNA was isolated from each patient and synthetic oligonucleotide primers were used in the polymerase chain reaction to amplify each exon, splice junction and polyadenylation site. Amplified DNA was then cloned into pUC18 and sequenced. Five novel point mutations were identified, two occurring in the eighth exon of the factor IX gene and three in the eighth exon of the factor X gene. One of the haemophilia B mutations and one of the factor X mutations altered homologous histidine residues near the serine of the catalytic triad.

Base Sequence↗

Characterization of Neisseria meningitidis isolates and clinical features of meningococcal conjunctivitis in ten patients.

Cases of meningococcal conjunctivitis occurring in Denmark in the period 1982-1991 were reviewed. In a survey of laboratory reports, ten cases were identified. The meningococcal strains were characterized by serological grouping, typing and subtyping, and by antimicrobial susceptibility testing. Five cases were caused by serogroup B meningococci (B:15:P1.16, B:15:P1.6, B:4:P1.15) and five cases by serogroup C meningococci (C:2a:P1.2 (4 strains), C:14:NST). The median age of the patients was 12.5 months (range 7 days to 9 years). Signs of conjunctivitis were predominant; in addition, five of the patients had fever and general malaise. In one patient the same strain was recovered from blood and eye secretions. None of the patients had signs of meningitis. All meningococcal strains isolated from patients with meningococcal conjunctivitis were assumed to be virulent and had the same characteristics as strains causing meningococcal disease in Denmark within the same period.

Child↗

Plasma nicotine, plasma beta-endorphin and mood states during periods of chronic smoking, abstinence and nicotine replacement.

Nicotine is known to release neuroendocrine substances which may subsequently reinforce smoking behavior by improving mood states. The purpose of this study was to examine changes in plasma beta-endorphin and mood states during periods of chronic smoking, abstinence from smoking, and abstinence while chewing nicotine gum. A modified A-B-A-C design was used. Normal male volunteers were randomly assigned to an experimental or control group. Over a 12-day protocol, experimental subjects smoked ad libitum for 2 days, were abstinent for 4 days, resumed smoking for 2 days, and then chewed nicotine gum for the final 4 days. Control subjects smoked ad libitum throughout the entire protocol. Results indicated that changes in plasma beta-endorphin levels were not related to changes in the four smoking conditions. Plasma nicotine and mood states were related, such that dysphoric moods increased during abstinence from smoking in comparison to the control group. To investigate further the relationships between nicotine, beta-endorphin and reinforcement for smoking, it may be necessary to characterize endogenous opioid peptide release in the central nervous system during smoking.

Adult↗

Discriminant function analysis of body surface potential maps in acute myocardial infarction.

Using a newly developed 64-electrode portable mapping device, QRS and ST-T isointegral maps were compared in 194 control subjects and 101 patients. One hundred ninety-four control subjects (mean age, 48 years; 120 men) with no history of cardiac disease were selected randomly and mapped. One hundred one patients (mean age, 62 years; 77 men) were mapped at presentation of chest pain suggestive of first myocardial infarction (MI); all patients had classic 12-lead electrocardiographic findings--46 with anterior and 55 with inferior MI. The diagnosis was confirmed in all cases by a significant rise in serial cardiac enzymes. The mean delay between onset of chest pain to map recording was 163 minutes. Of the 101 patients, 78 were first mapped outside the hospital. Applying discriminant function analysis to the isointegral measurements made on the control subjects and on the first map of MI patients achieved a correct classification of 97% of the control subjects (189 of 194) and 72% of the anterior (33 of 46) and 76% of the inferior (42 of 55) MI groups. This preliminary study suggests that discriminant function analysis, based on isointegral maps, not only provides a method of separating control subjects from MI patients but that it can also differentiate between types of infarct. Further studies are required to improve the predictive values of discriminant function and to extend the methodology to assess both the site and size of MI.

Adult↗

Efficacy of felbamate in therapy for partial epilepsy in children.

Thirty children (2 to 17 years of age) with refractory partial seizures received open-label felbamate as an add-on medication to their background antiepileptic drugs. The dose was increased up to a maximum of 45 mg/kg. Compared with baseline seizure activity, there was a 53% decrease in seizure frequency during felbamate therapy; 50% of the patients had more than a 50% decrease in seizure frequency. Patients older than 10 years of age were more likely to have a favorable response. Age correlated positively with felbamate concentrations and negatively with apparent felbamate clearance. Transient weight loss occurred in 57% of the patients; the weight loss was maximal after 12 weeks of initiation of felbamate, and subsided after the twentieth week of treatment. Anorexia and insomnia were reported in 20% and 16% of the patients, respectively. Adverse effects were generally tolerable; felbamate therapy was discontinued because of side effects in only one patient, because of a rash. We conclude that felbamate can be a useful and well-tolerated medication in the treatment of refractory partial epilepsy in children. However, increased apparent clearance of this drug in younger children should be considered in treatment of this age group.

Adolescent↗

Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian Natives.

We describe eleven mid-western Canadian aboriginal infants with a unique, progressive muscle disorder. All except one had muscle biopsy and/or autopsy. The infants were normal newborns who rapidly developed rigidity of all skeletal muscles, with early, respiratory insufficiency. Death occurred before 18 months of age. Electromyography showed increased insertion activity and profuse fibrillation potentials; motor unit potentials and interference pattern are normal until late in the course. Pathologic features include progressive, granular to powdery Z-band transformation, myofibrillar loss, and muscle regeneration. SDS-gel electrophoresis of one muscle sample revealed increased 54kDa and reduced 80kDa protein fractions. This disease differs from other conditions with Z-band alterations because of continuous muscle activity and relentless clinical progression. The clinical features, elevated serum creatine kinase, electromyographic and muscle biopsy findings suggest a dystrophic process. The recognition of this condition as an autosomal recessive disorder allows appropriate genetic counselling.

Canada↗