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Biomedical subjects

A Anderson

Publications and source records attributed to A Anderson.

At least 235 records · Page 13Linked to original sources

Fasciola hepatica: studies on vaccination of rats and mice with a surface antigen prepared from fluke homogenate by means of a monoclonal antibody.

T1 tegumental antigen was isolated from a homogenate of eight- to 10-week-old Fasciola hepatica using a T1-specific monoclonal antibody bound to sepharose in an antibody-affinity column. Rats and mice were vaccinated with T1 antigen in Freund's complete adjuvant, and control groups received equivalent amounts of non-T1 antigen (eluted from the antibody-affinity column) or ovalbumin. On completion of the immunisation programme, serum samples were collected for ELISA and IFA testing. The animals were challenged by oral infection with F hepatica metacercariae or, for several vaccinated rats, by intraperitoneal transplantation of live adult flukes. At autopsy, worm-burden and liver damage was assessed for each animal and the condition of transplanted flukes was examined. Comparison of test and control groups of animals showed that neither T1 nor non-T1 antigens provided significant protection against challenge, although specific antibody responses against the appropriate sensitising antigen were engendered. Flukes transplanted to the peritoneal cavity of immunised rats survived without damage, although they became encased in hollow fibrous capsules of host origin. The results lend support to the pre-existing concept that glycocalyx turnover by discharge of T1 secretory bodies at the apical surface of migrating flukes provides an efficient means of protection for the parasite against host immunity.

Animals↗

Use of immunosorbent-purified antigens of Fasciola hepatica in enzyme immunoassays.

A monoclonal antibody specific for the T1 tegumental antigen of Fasciola hepatica was used as a solid-phase immunosorbent for the purification of T1 antigen from homogenised mature F hepatica. Material fractionated by this technique was successfully used in enzyme-linked immunoassays to detect antibodies to F hepatica in sera from sheep and cattle. Species differences in response to infection by F hepatica were demonstrated.

Animals↗

Use of sodium restriction and enalapril in persons with moderate to severe hypertension.

One hundred and seventy-four patients who were receiving drug therapy for hypertension were asked to restrict their sodium intake for three months. At the end of that time their drug therapy was replaced with enalapril and the dose of the drug "titrated" to obtain a diastolic blood pressure of less than 90 mmHg. Sodium restriction caused a small fall in blood pressure and could be used as sole therapy in only 6% of patients. Enalapril therapy was instituted without problems and control of blood pressure below 90 mmHg was achieved in 62% of persons with monotherapy. The number of tablets of enalapril that were taken was reduced from 5.9 to 2.7; in most patients these were taken once a day. There were few side-effects and no depression of white cell count, no proteinuria and no deterioration of renal function. Seventy-six per cent of patients preferred the new regimen either because they felt better than with their previous therapy (52%) or because of the more simple regimen (24%). Enalapril was an effective, well tolerated antihypertensive agent and potentially has a major role to play in the management of patients with high blood pressure.

Antihypertensive Agents↗

Benzodiazepine sensitivity testing in the management of intractable seizure disorders in childhood.

The use of benzodiazepine sensitivity testing in the management of 40 children with intractable seizure disorders was studied. The aetiology and clinical syndromes varied widely with myoclonic, atonic and complex absence seizures predominating. Twenty-five cases had mixed seizure disorders. There was, likewise, a wide range of EEG abnormalities. Seven cases were in non-convulsive status at the time of testing. Diazepam (0.2 mg/kg) was given slowly intravenously and its effect on the EEG was observed. In 21 cases epileptiform activity was abolished. No change was seen in 13 cases and an unusual result was seen in 3. There was a paradoxical response in 3 cases, two of these associated with clinical seizures. Only 1 child in non-convulsive status had a positive result. Following testing, 32 patients went on to long-term oral benzodiazepine treatment. Twenty-one of these patients showed subsequent clinical improvement and 16/21 (76%) had had a positive sensitivity test previously. Eleven of these patients did not improve on long-term treatment. Seven out of the 11 (64%) had had a negative sensitivity test. These results suggest that the benzodiazepine sensitivity test is of value in the long-term management of intractable seizure disorders in childhood, but also emphasise the variability and unpredictability of response to benzodiazepine treatment.

Adolescent↗

The pattern of management after stroke.

A large population-based study of stroke is used to describe the pattern of management and the relative contribution of hospital care and community care in the year following an acute stroke episode. Two thirds of the 680 patients registered in the study were admitted to a public hospital during the acute stage of their illness, while almost one quarter of all patients were managed entirely at home. One month after the initial episode the majority of patients admitted to hospital had either died or had been discharged. Overall, four-fifths of the care during the first year after the onset of the stroke took place out of hospital, either at home or in private long-term institutions.

Adolescent↗

The effect of perindopril on blood pressure in humans on different sodium intakes.

Perindopril is a new inhibitor of converting enzyme activity with a prolonged half-life. Thirty-two patients with essential hypertension and a diastolic blood pressure greater than 95 mm Hg were stratified into two groups according to their 24 h urine sodium excretion. They were randomized in a double-blind fashion to placebo or perindopril and a dose titration made in steps of 2, 4, 6, and 8 mg given once daily at weekly intervals. The goal diastolic blood pressure was 90 mm Hg. Goal blood pressure was achieved in 11 of 16 patients on perindopril and 3 of 6 patients on placebo. Perindopril caused a fall in BP of 22/11 (supine) and 27/14 (erect) mm Hg while the placebo group had falls of 3/2 (supine) and 3/0 (erect) mm Hg. Most of the blood pressure fall occurred in the first week of therapy with 2 mg/day. Side effects were few and occurred mainly in the placebo phase. There was no alteration in urine protein, white cell count, plasma urea, or creatinine. The fall in blood pressure achieved at the end of the titration or with 2 mg did not differ between the two groups. There was no correlation between blood pressure response and 24 h urine sodium or plasma renin activity. These results indicate that perindopril is an effective antihypertensive drug that appears to work equally well in patients on high or low sodium intake.

Aged↗

Sodium restriction can delay the return of hypertension in patients previously well-controlled on drug therapy.

Sodium restriction can reduce blood pressure in hypertensive patients. The present study indicates that if hypertension is well controlled then the reemergence of hypertension can be decreased by the use of a reduced sodium intake. The present paper demonstrates that in such patients on a normal salt diet, 90% become hypertensive within 6 months while only 40% of people on a reduced sodium diet become hypertensive. It is proposed that a high sodium intake activates a number of amplifiers that causes a shift of the dose-response curve to sodium to the left and if not prevented or interrupted leads to the development of hypertension.

Aged↗

Felodipine versus prazosin as an addition to a beta-blocker in the treatment of essential hypertension. The Australian Multicentre Study.

The efficacy and tolerability of felodipine and prazosin were compared in a double-blind randomised parallel group study of 100 patients with moderately severe essential hypertension, treated concomitantly with a beta-blocking drug. After a 2- to 8-week run in phase (beta-blocking drug plus placebo), patients with a diastolic blood pressure greater than or equal to 95mm Hg were randomly given felodipine (n = 50) or prazosin (n = 50). After an initial dose of either felodipine 2.5mg bid or prazosin 0.5mg bid for 3 days, the drugs were titrated at 2-week intervals (felodipine 5, 10, 20mg bid, prazosin 1, 2, 4mg bid) if the supine diastolic blood pressure was greater than or equal to 90mm Hg. Treatment was continued for 8 weeks. Baseline supine blood pressures of each group were similar (177/104mm Hg, felodipine; 176/103mm Hg, prazosin). At week 6, supine blood pressures in the felodipine group were 144/82mm Hg and 161/90 in the prazosin group. The reductions in systolic and diastolic blood pressures were significantly greater for the felodipine group than the prazosin group in both the supine and standing positions at all visits after baseline. At 8 weeks, supine diastolic blood pressure less than 90mm Hg was achieved in more patients in the felodipine (36/47) than in the prazosin group (20/43, p less than 0.01). The total number of adverse reactions was similar in both groups. During active therapy, a greater number of patients experienced vascular adverse reactions (oedema and flushing) with felodipine (23) than with prazosin (12). Most events were mild and did not necessitate withdrawal from therapy. There were no clinically significant changes in laboratory variables in either treatment group. Felodipine was an effective, well tolerated hypotensive agent when used concomitantly with a beta-blocking drug. In the doses used it was more effective than prazosin at reducing blood pressure.

Adrenergic beta-Antagonists↗

Environmental pollutant and necropsy data for ospreys from the eastern United States, 1975-1982.

Twenty-three ospreys (Pandion haliaetus) found dead or moribund in the eastern United States during 1975-1982 were necropsied and selected tissues were analyzed for organochlorines and metals. Major causes or factors contributing to death were trauma, impact injuries, and emaciation. DDE was detected in 96% of the osprey carcases, DDD in 65%, DDT and heptachlor epoxide in 13%, dieldrin, oxychlordane, and cis-nonachlor in 35%, cis-chlordane in 52%, trans-nonachlor in 45%, and PCB's in 83%. Carcasses of immature ospreys from the Chesapeake Bay had significantly lower concentrations of DDE, DDD + DDT, cis-chlordane, and PCB's than carcasses of adults from the same area. Concentrations of some organochlorines in ospreys from the Chesapeake Bay declined significantly from 1971-1973 to 1975-1982. Significant differences in concentrations of certain metals in the ospreys' livers were noted between time periods, and sex and age groups for birds from the Chesapeake Bay. During 1975-1982, adults had significantly lower concentrations of chromium, copper, and arsenic than immatures and nestlings, and adult males had higher mercury concentrations than adult females. Adult females had lower zinc concentrations in 1975-1982 than in 1971-1973. Immatures and nestlings had higher concentrations of chromium and lead in 1975-1982 than in 1971-1973. A slightly elevated concentration of chromium (1.7 ppm) or arsenic (3.2 ppm) was found in the livers of individual ospreys. Several ospreys had elevated concentrations of mercury in their livers; two ospreys had more than 20 ppm which may have contributed to their deaths.

Animals↗

Immunopathology of acute experimental histoplasmic choroiditis in the primate.

The immunopathologic features of experimental acute histoplasmic choroiditis were studied in the nonhuman primate. Using an indirect immunoperoxidase technique, a panel of hybridoma-derived anti-human monoclonal antibodies, recognizing distinct lymphoid cell and macrophage surface antigens, have been adapted for use in the primate system. Twenty-two individual foci of histoplasmic choroiditis from five eyes were studied at time periods from 20 to 60 days post intracarotid injection of yeast phase Histoplasma capsulatum. A mononuclear and granulocytic cell infiltration was seen in all lesions. The predominant cell type was the CAPPEL+ T lymphocyte (suppressor/cytotoxic subset). Other cell types found in smaller numbers were OKT4+ T cells (helper/inducer subset), OK7+ (peripheral B lymphocytes), IgD+ (mantle B cells) and OKM1+ cells (macrophages and polymorphonuclear leukocytes). Herein, we present immunopathologic data on the acute phase of experimental ocular histoplasmosis.

Acute Disease↗

Estrogen receptors and growth response in cultured human periodontal ligament cells.

The periodontal ligament (PDL) is a connective tissue involved in the remodeling process associated with tooth development and positioning. PDL cells grown in culture were analyzed for the capacity to specifically bind steroid hormones and for growth response to estradiol-17 beta. Using [3H]estradiol-17 beta as the ligand, PDL cells in first passage cultures exhibited a specific estrogen binding capacity of 881 fmol/mg cell protein. With [3H]dexamethasone as a ligand, the binding capacity of the glucocorticoid receptor was 143 fmol/mg protein. With [3H]R5020 as a ligand, the progestin receptor exhibited a binding capacity of 5 pmol/mg protein. Scatchard analysis of estradiol binding at 37 degrees revealed a dissociation constant of 2.7 X 10(-9) M, representative of the estrogen receptor. The addition of estradiol-17 beta at concentrations of 10(-9) and 10(-8) M to culture media induced a dose-dependent decrease in growth (DNA content) to 62% and 38% control values, respectively. The addition of the antiestrogens tamoxifen and 4-hydroxytamoxifen at concentrations of 10(-7) and 10(-6) M similarly depressed cell growth. These results show that PDL cells contain high affinity receptors for several steroid hormones and further that these cells are targets for the action of estrogens.

Adult↗

Production and characterization of monoclonal antibodies against the two subunits proteins B1 and B2 of Escherichia coli ribonucleotide reductase.

Ribonucleotide reductase from Escherichia coli consists of two nonidentical subunits, named protein B1 (170 000) and protein B2 (87 000). We purified and characterized five monoclonal antibodies against B1 and three against B2 from hybridomas obtained by fusion of spleen cells from immunized mice and the myeloma cell line P3-X63Ag8. All are of the IgG1 class with a high affinity for the antigen with dissociation constants in the nanomolar range. Four of the anti-B1 monoclonals and all three anti-B2 monoclonals neutralize reductase activity while one anti-B1 monoclonal binds tightly to B1 without affecting its activity. Fab fragments prepared from three anti-B1 monoclonals had similar dissociation constants. The anti-B1 monoclonals interacted with separate epitopes while two of the anti-B2 monoclonals appeared to react with the same epitope. In the case of B1, various allosteric states of the protein induced by binding of effectors had no apparent effect on the interaction with monoclonals, nor did their binding prevent subsequent binding of effectors. With B2, binding of monoclonals did not affect the typical electron paramagnetic resonance spectrum of the protein and thus did not involve either the tyrosyl free radical or the iron center of B2. All neutralizing antibodies interfered with the interaction between the two subunits, explaining their effect on enzyme activity, since active ribonucleotide reductase consists of a B1-B2 complex.

Animals↗

Affinity chromatography on anti-B1 monoclonal gels for purification and characterization of protein B1 from Escherichia coli ribonucleotide reductase.

Affinity gels were prepared from four monoclonal antibodies against the B1 protein of ribonucleotide reductase of Escherichia coli. The gels were used to purify protein B1 and also to study some of its properties. Gels from the nonneutralizing monoclonal anti-B1-k bound as much as 2 mg of B1/mL and were employed to prepare essentially pure B1 protein in a single step from extracts of wild-type E. coli and strains overproducing the subunit. However, B1 prepared from wild-type extracts had a lowered specific activity, suggesting some denaturation during elution of the protein from the column. Addition of the allosteric effector dATP during affinity chromatography changed the chromatographic pattern. Some protein B2, the second subunit of the reductase, remained in all cases bound to the gels together with B1. The gel prepared from anti-B1-c retained two additional proteins. In other experiments involving binding of proteolytic fragments of B1 to various antibodies, we also found a striking effect of dATP, suggesting that dATP made protein B1 less accessible to proteolysis. In these experiments fragments around 15K still had the ability to bind monoclonals, making possible more detailed investigations of the structural contacts between B1 and the monoclonals.

Antibodies, Monoclonal↗