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Biomedical subjects

E Smith

Publications and source records attributed to E Smith.

At least 307 records · Page 17Linked to original sources
PubMed1987

Bradyrhizobium japonicum mutants defective in nitrogen fixation and molybdenum metabolism.

Bradyrhizobium japonicum JH mutants deficient in molybdenum metabolism into the enzymes nitrogenase and nitrate reductase were isolated by using the vector pSUP1011, which carries transposon Tn5 (streptomycin and kanamycin resistance). Mutants in Mo metabolism were obtained at a frequency of 3.6 X 10(-3) (per Kan Strr colony). The mutants were detected by their poor ability to grow in nitrate-containing medium without added Mo. One of the mutant types required 10(5) times more molybdate than the wild type to obtain maximal nitrogen fixation activity. Double-reciprocal plots of Mo uptake versus concentration indicated that the wild-type strain had a high- and a lower-affinity component for Mo binding. Mutant strains JH-90 and JH-119 lacked the high-affinity Mo uptake component and were also clearly deficient in Mo accumulation into a nonexchangeable form. Nitrogenase activity as well as Mo uptake ability could be restored in strains JH-90 and JH-119 by the addition of the sterile supernatant fraction of the wild type. Therefore, mutant strains JH-90 and JH-119 appeared to be deficient in an extracellular Mo-binding factor produced by the wild type. Mutant strains JH-14 and JH-143 had Mo uptake kinetics like those of the wild type (both high- and low-affinity binding for Mo) and appeared to be deficient in intracellular Mo metabolism processes. The addition of the wild-type supernatant did not restore Mo uptake or nitrogenase activity in these strains.

Biological Transport↗
PubMed1987

A formyl peptide contracts guinea pig lung: role of arachidonic acid metabolites.

We studied the role of cyclooxygenase and lipoxygenase products of arachidonic acid metabolism in mediating N-formyl-methionyl-leucyl-phenylalanine- (FMLP) induced contractions of guinea pig lung parenchymal strips. The cyclooxygenase inhibitors indomethacin (10(-5) M) and aspirin (3 X 10(-5) to 10(-4) M), the lipoxygenase inhibitor nordihydroguaiaretic acid (10(-5) to 3 X 10(-5) M), and the combined cyclooxygenase/lipoxygenase inhibitors 1-phenyl-3-pyrazolidinone (Phenidone) (3 X 10(-5) to 3 X 10(-4) M) and BW 755C (10(-5) to 10(-4) M) each caused a decrease in the maximum force induced by FMLP (Fmax) and an increase in the concentration of FMLP required to produce 50% of Fmax (EC50). The thromboxane synthesis inhibitor imidazole (3 X 10(-3) M) also decreased Fmax. The leukotriene D4 receptor antagonist FPL 55712 (5.7 X 10(-6) to 1.9 X 10(-5) M) increased the EC50 for FMLP, whereas desensitization of lung parenchymal strips to leukotriene B4 by pretreatment with this leukotriene (10(-7) M) had no effect on FMLP-induced contraction. After exposure to FMLP (10(-6) M), guinea pig lung produced (as determined by high-performance liquid chromatography and radioimmunoassay) leukotrienes C4 and B4, thromboxane A2 (as measured by its stable degradation product thromboxane B2), and prostaglandin F2 alpha. Lung strips not exposed to FMLP showed no evidence of leukotriene production. We conclude that thromboxane A2 and leukotriene C4 generated in response to FMLP mediate a substantial fraction of the force induced by this peptide in guinea pig lung parenchymal strips.

Acetophenones↗
PubMed1987

Skin as the site of vitamin D synthesis and target tissue for 1,25-dihydroxyvitamin D3. Use of calcitriol (1,25-dihydroxyvitamin D3) for treatment of psoriasis.

Vitamin D is a hormone, not a vitamin. The skin is responsible for producing vitamin D. During exposure to sunlight, ultraviolet radiation penetrates into the epidermis and photolyzes provitamin D3 to previtamin D3. Previtamin D3 can either isomerize to vitamin D3 or be photolyzed to lymisterol and tachysterol. Vitamin D is also sensitive to sunlight and is photolyzed to 5,6-transvitamin D3, suprasterol I, and suprasterol II. In Boston, solar irradiation only produces previtamin D3 in the skin between the months of March and October. Aging, sunscreens, and melanin all diminish the capacity of the skin to produce previtamin D3. Once formed, vitamin D3 enters the circulation and is sequentially metabolized to 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 (1,25-[OH]2-D3). The epidermis possesses receptors for 1,25-(OH)2-D3. 1,25-(OH)2-D3 inhibits the proliferation of cultured keratinocytes and induces them to terminally differentiate. The topical or oral administration of 1,25-(OH)2-D3 has proved to be effective for the treatment of psoriasis. Therefore, the skin is the site for the synthesis of vitamin D and a target tissue for its active metabolite. The successful use of 1,25-(OH)2-D3 for the treatment of psoriasis heralds a new approach for the treatment of this enigmatic disorder.

Calcitriol↗
PubMed1987

Experimental autoimmune thyroiditis: attempt to correlate disease development with lymphocyte subset changes.

An attempt was made to correlate lymphocyte subset abnormalities with the development of experimental autoimmune thyroiditis (EAIT) in thymectomized and irradiated rats of five inbred strains. The peripheral blood subpopulations were analysed using the fluorescence-activated cell sorter (FACS-IV). A significant lymphopenia with a severe decrease in helper T cells was identified in all the treated rats. In addition, a significant loss of suppressor cytotoxic T cells was found in rats of the most susceptible strain (August) and in the majority of affected individual rats of the other strains. The simple, modified protocol which we used revealed differences in strain susceptibility to EAIT, with 66% of August rats having histological evidence of disease, 50% of Lewis, 44% of Agus, 30% of Hooded Lister and 20% of Wistar, at 5 to 8 months after treatment. Levels of antithyroglobulin antibody, estimated by an ELISA assay, correlated well with the histological results. In all groups, three times as many females as males were affected. Our findings support the view that genetic and immunoregulatory factors are involved in the development of EAIT, with loss of both helper and suppressor cells playing an important role.

Animals↗
PubMed1987

Angiotensin converting enzyme inhibitory activity of SCH 33844 (spirapril) in rats, dogs and monkeys.

SCH 33844 is a new non-sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor. SCH 33844 diacid inhibited hydrolysis of the synthetic substrate hippuryl-histidyl-leucine by rabbit lung ACE in vitro with an IC50 (concentration inhibiting enzyme by 50%) of 0.81 nM. The ester was 83 times less active. Intravenous administration of SCH 33844 and its diacid inhibited pressor responses to angiotensin I (AI) in anesthetized rats with calculated ID50's of 16 and 8 micrograms/kg, respectively. Oral administration of SCH 33844 (0.03-1 mg/kg) inhibited AI pressor responses in conscious rats with a duration of 24 hr at the highest dose. The diacid was inactive. Intravenous administration of SCH 33844 (100-1000 micrograms/kg) or its diacid (30 micrograms/kg) to anesthetized dogs inhibited AI pressor activity and potentiated the depressor response to bradykinin. SCH 33844 inhibited AI responses in conscious dogs following oral administration of 0.3-3 mg/kg. Oral administration of SCH 33844 (1 mg/kg) to conscious monkeys inhibited AI pressor responses for the 4 hr duration of study. In conclusion, SCH 33844 is a potent, orally effective ACE inhibitor in rats, dogs and monkeys.

Angiotensin I↗
PubMed1986

Asymptomatic children with epilepsy: little benefit from screening for anticonvulsant-induced liver, blood, or renal damage.

In a prospective study of 199 asymptomatic children receiving anticonvulsant drugs, we evaluated routine screening for liver, renal, and hematologic toxicity. Urinalysis, CBC, differential, platelets, SGOT, bilirubin, and alkaline phosphatase (plus amylase and fibrinogen in patients taking valproate) were obtained between 0 and 24 months. Compliance was excellent. Urine was always normal. Six percent of patients had transient minor abnormalities of blood studies necessitating rechecks. All were normal on repeat. Two children had major blood abnormalities recognized, leading to drug changes that proved to have been unnecessary. Baseline determinations and prompt attention to symptoms of toxicity should replace routine screening of blood and urine.

Adolescent↗
PubMed1985

Effect of amitriptyline on the thyrotropin response to thyrotropin-releasing hormone in endogenous depression.

Patients with endogenous depression whose depressive episodes were clinically resolved after electroconvulsive therapy were divided into two groups: one in which patients remained well (n = 16) and another in which patients relapsed within 6 months (n = 11). Treatment with amitriptyline for 3 weeks did not affect the median thyrotropin (thyroid-stimulating hormone; TSH) response to thyrotropin-releasing hormone (TRH) in recovered patients, whereas that in relapsed patients was significantly enhanced. The data suggest that amitriptyline affects the TSH response to TRH differently in stably recovered and relapsed patients. If this effect is maintained beyond the 3-week period studied, treatment with amitriptyline will invalidate the predictive value of the TRH test.

Aged↗
PubMed1985

Cultured psoriatic fibroblasts from involved and uninvolved sites have a partial but not absolute resistance to the proliferation-inhibition activity of 1,25-dihydroxyvitamin D3.

We examined the responsiveness of cultured dermal fibroblasts from biopsies of uninvolved and involved areas of skin from six patients with psoriasis to the cell-proliferation-inhibition activity of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3). Cultured fibroblasts from age-matched controls responded to 1,25-(OH)2-D3 (at 0.01, 1, 10, and 100 microM) in a dose-dependent fashion, whereas cultured psoriatic fibroblasts from involved or uninvolved skin showed no inhibition of proliferation when exposed to 0.01 or 1 microM of 1,25-(OH)2-D3. However, 1,25-(OH)2-D3 did inhibit proliferation of cultured psoriatic fibroblasts when the concentrations were increased to 10 and 100 microM. An analysis of the 1,25-(OH)2-D3 receptors in cultured psoriatic fibroblasts from uninvolved skin revealed that the Kd, nmax, and sedimentation coefficient were identical to the receptors found in the fibroblasts from age-matched controls. Therefore, cultured psoriatic fibroblasts from involved and uninvolved skin have a partial resistance to 1,25-(OH)2-D3, suggesting that there may be a biochemical defect that is inherent in the dermal fibroblasts of psoriatic patients. Recognition of this defect may provide a new approach for the evaluation of the cause and treatment of this disfiguring skin disorder.

Calcitriol↗
PubMed1985

Reduced 2',3'-cyclic nucleotide 3'-phosphohydrolase activity in erythrocyte membranes of patients with multiple sclerosis.

2',3'-Cyclic nucleotide 3'-phosphohydrolase (CNPase) activity is reduced in myelin during multiple sclerosis. Therefore, we have investigated whether the enzyme is also depressed in non-neural membranes during this disease. MS and control erythrocyte membranes and whole lymphocytes were assayed for CNPase activity. The MS erythrocyte membrane preparations were found to exhibit up to 45% lower CNPase levels than the controls (P less than 0.02). There was no significant difference in the lymphocyte CNPase levels in MS and control groups. When control erythrocyte membrane preparations were assayed in the presence of MS plasma they were inhibited 100% by MS (but not by control) plasma. These data suggest that erythrocyte membrane CNPase activity is significantly reduced in MS patients and that the reduction in activity may be due to an inhibitor present in MS plasma.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1984

Efficacy and safety of intravenous tocainide compared with intravenous lidocaine for acute ventricular arrhythmias immediately after cardiac surgery.

In this double-blind parallel study, 99 patients with acute ventricular tachyarrhythmias after open-heart surgery were given either tocainide (50 patients) or lidocaine (49 patients) intravenously as 2 bolus injections 15 minutes apart, plus a fixed-rate infusion that started at the first bolus. If needed, a third bolus was administered and simultaneously the infusion rate was doubled. The boluses and initial infusion rate for tocainide treatment were, respectively, 250, 250 and 125 mg and 1.04 mg/min, and for lidocaine treatment, 100, 50 and 50 mg and 2.08 mg/min. When efficacy was defined as 80% or greater reduction in single ventricular premature complexes (VPCs) or complete abolition of ventricular couplets or ventricular tachycardia, no difference in efficacy between the 2 treatments was found by bedside electrocardiographic monitoring. By computer analysis of 24-hour taped electrocardiograms and a regression analysis of the proportion of patients responding favorably to treatment, it was estimated that an 80% or greater reduction of single VPCs occurred in 55% of patients during tocainide treatment and in 48% of patients during lidocaine treatment; abolition of couplets occurred in 74% and 68% of patients, respectively; and abolition of ventricular tachycardia in 87% and 73% of patients, respectively. These treatment-related differences were different (p less than 0.004). Adverse reactions occurred in 5 patients (10%) given tocainide (hypotension in 4; junctional rhythm in 1 patient; and nausea-vomiting in 1) and led to discontinuation of treatment in 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗