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Biomedical subjects

B F Johnson

Publications and source records attributed to B F Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Differential effects of glucocorticoids on insulin-like growth factor I action in cultured human fibroblasts.

Glucocorticoids act synergistically with insulin-like growth factor I (IGF-I) to stimulate DNA synthesis and replication of cultured human fibroblasts. In the present study, we further define glucocorticoid and IGF-I interactive effects on human fibroblast metabolism and growth. IGF-I stimulated dose-dependent increases in early metabolic events. Half-maximal effectiveness was seen at 5-8 ng/ml IGF-I, with mean maximal responses of 1.5-, 2-, and 6-fold for [3H]2-deoxyglucose uptake, [14C]glucose incorporation, and [14C]aminoisobutyric acid (AIB) uptake, respectively. A 48-hour preincubation with 10(-7) M dexamethasone markedly enhanced both the sensitivity and maximal effectiveness of IGF-I stimulation of AIB uptake. In contrast, dexamethasone had no effect on IGF-I-stimulated glucose uptake and utilization. Maximum specific binding of [125I]IGF-I to fibroblast monolayers was identical in ethanol control and glucocorticoid-treated cells, with 50% displacement at approximately 5 ng/ml IGF-I. In addition to its synergism with IGF-I, preincubation with dexamethasone augmented insulin and epidermal growth factor (EGF) stimulation of [3H]thymidine incorporation; dexamethasone had no effect on platelet-derived growth factor or fibroblast growth factor action. Two-dimensional gel electrophoresis identified two specific glucocorticoid-induced proteins in human fibroblast cell extracts with molecular weights of 45K and 53K and pIs of 6.8 and 6.3, respectively. These data indicate that IGF-I receptor-mediated actions in human fibroblasts are differentially modulated by glucocorticoids. Glucocorticoids are synergistic with IGF-I in stimulating mitogenesis and amino acid uptake, without having any apparent effect on IGF-I-stimulating glucose metabolism. Glucocorticoid enhancement of growth factor bioactivity may involve modulation of a regulatory event in the mitogenic signaling pathway subsequent to cell surface receptor activation.

Aminoisobutyric Acids↗
PubMed1995

Smashed fission yeast walls. Structural discontinuities related to wall growth.

Twenty-three samples of fission yeast cells (Schizosaccharomyces pombe) were smashed by shaking them with glass beads. The samples represented all phases of the culture cycle, with the lag and log phases emphasized. Ruptured walls of the smashed cells were observed by phase-contrast and electron microscopy. Ruptures were tabulated with respect to their magnitudes and locations. Ruptures occurred not at random, nor at sites directed by geometry, but predominated in certain definable wall regions. These discontinuities were correlated with morphogenetic activities of the cell. Thus, the extensile end was found to be most fragile through most of the culture cycle. Also fragile was the nonextensile end, its edge more than its middle. Further, the data were applied to the testing of predictions from extant models (Johnson endohydrolytic softening model and Wessels presoftened-posthardened and crosslinking model) for hyphal tip extension. The frequency of rupture at the extensile (old) end of the cell was qualitatively predicted by both models; the frequency at the nonextensile (new) end was not predictable by either. Rupture frequencies and characteristics at other regions conformed to predictions by one or the other model, but rarely by both.

Cell Cycle↗
PubMed1995

Clinical outcome in patients with mild and moderate carotid artery stenosis.

PURPOSE: The natural history of incidentally discovered asymptomatic mild (< 50%) and moderate (50% to 79%) carotid artery stenosis is not known. The carotid artery duplex ultrasound surveillance program at the University of Washington Department of Vascular Surgery has serially evaluated patients with carotid artery disease for more than a decade and provides data on the progress and management of this disease. METHODS: Patients with asymptomatic carotid artery bruits who had carotid artery disease causing less than 80% lumen diameter narrowing at their initial visit were identified. At each return visit (6 months, 1 year, and annually thereafter) a clinical questionnaire was completed, and bilateral carotid artery duplex sonography was performed. RESULTS: Two hundred thirty-two patients (136 men and 96 women) were monitored for up to 10 years with sufficient data for a 7-year life-table analysis. Progression in the degree of stenosis was noted in 23% of patients during follow-up, and nearly half of these progressed to severe stenosis (80% to 99%) or occlusion. The risk of progression to severe stenosis and occlusion was significantly greater for those patients with moderate initial stenosis than mild initial stenosis (p < 0.01). The cumulative stroke risk for patients with mild initial stenosis (6%) was half of that for patients with moderate initial stenosis (11%) after 7 years. Carotid endarterectomy was performed in 27 patients during follow-up; in 13 the indication was an event ipsilateral to the stenosis, and in 14 there was asymptomatic progression to high-grade stenosis. CONCLUSIONS: Regular monitoring of mild to moderate carotid artery stenosis shows how these lesions progress over time, permitting a realistic appraisal of their potential for producing an ischemic cerebrovascular event.

Aged↗
PubMed1995

Relationship between changes in the deep venous system and the development of the postthrombotic syndrome after an acute episode of lower limb deep vein thrombosis: a one- to six-year follow-up.

PURPOSE: This study investigated changes in the deep venous system and the development of the postthrombotic syndrome (PTS) after an episode of acute deep vein thrombosis (DVT). METHODS: Seventy-eight patients (41 male patients, 37 female patients) with acute DVT in 83 legs (31 right, 42 left, five bilateral) underwent annual follow-up examinations for 1 to 6 years (median, 3 years) for symptoms and signs of the PTS. A venous duplex scan was performed at each visit to detect obstruction and reflux in the veins, both of which may contribute to the development of the PTS. DVT was primary in 69 limbs and recurrent in 14 limbs. RESULTS: When last examined 49 limbs were free of symptoms, and 34 had the PTS (23 edema only, 11 hyperpigmentation). Only two patients had ulcers during the follow-up period; both patients had the ulcers in areas of hyperpigmentation in limbs with recurrent DVT. The extent of disease was similar in limbs with the PTS (79% multisegment, 18% single segment) and those without the PTS (69% multisegment, 12% single segment). In limbs with the PTS the deep veins were normal in only one (3%), six (18%) showed reflux only, five (15%) obstruction only, and 22 had features of both obstruction and reflux (65%). In limbs without the PTS the deep veins showed no abnormality in nine (18%), reflux only in 17 (35%), obstruction only in six (12%), and reflux with obstruction in 17 (35%). In the 11 limbs with hyperpigmentation nine had obstruction and reflux noted, one had obstruction only, and one had reflux alone. CONCLUSIONS: After an episode of acute DVT 12% of the limbs returned to normal by duplex criteria. Although only 13% developed skin complications, 41% had features of the PTS. Limbs with the PTS had more than three times the odds of having combined reflux and obstruction than did limbs without the PTS (odds ratio = 3.5, 0.95 confidence intervals = 1.4, 8.6). Continued study of these patients will determine the course of those limbs with venous abnormalities that have not yet developed symptoms and signs of the PTS.

Acute Disease↗
PubMed1995

Surgery for limb threatening ischaemia: a reappraisal of the costs and benefits.

OBJECTIVES: To study the quality of life of patients following surgery for critical limb is ischaemia. DESIGN: Part retrospective, part prospective open study. SETTING: Vascular unit of a University Hospital. MATERIALS: Seventy-nine consecutive patients, medium age 75 years (range 44 to 94), who presented with leg threatening ischaemia and who underwent successful revascularisation or a major amputation were studied. CHIEF OUTCOME MEASURES: Six separate quality of life measures were recorded at 6 months: pain, mobility, anxiety, depression, activities of daily living (Barthel) and lifestyle (Frenchay). MAIN RESULTS: The mortality of this group of patients after six months was 24%. Forty-seven patients were available for quality of life assessment six months after initial intervention. Overall, amputation was more costly than successful revascularisation and limb salvage. Limb salvage resulted in greater mobility (p < 0.001) and better performance in self-care (p < 0.001) and lifestyle (p = 0.006), but produced more anxiety and depression (p = 0.04) than major amputation. A subgroup of patients who had major amputation after a failed limb salvage operation consumed a disproportionate amount of resources and, although their mobility was typical of amputees, their self-care and lifestyle scores were similar to those who had successful limb salvage. OBSTRUCTIONS: Limb salvage is attempted in up to 22% of patients for whom primary amputation may provide more expeditious rehabilitation with minimal impairment of their lifestyle performance.

Activities of Daily Living↗
PubMed1994

Low-dose combined therapy with fluvastatin and cholestyramine in hyperlipidemic patients.

OBJECTIVE: To compare the low-density lipoprotein (LDL) cholesterol-lowering efficacy of low-dose combinations of cholestyramine and fluvastatin. DESIGN: Randomized, double-blind, parallel group, placebo-controlled trial with a 24-week double-blind treatment period divided into three phases. SETTING: Office-based clinics. PATIENTS: Hypercholesterolemic, with LDL cholesterol of 4.14 mmol/L or greater (> or = 160 mg/dL) and plasma triglycerides of 3.39 mmol/L or less (< or = 300 mg/dL). Four hundred sixty patients were screened; 224 patients were randomized into a double-blind treatment period; 203 completed the study; 6 dropped out because of adverse events. INTERVENTION: Patients were treated with 10 mg or 20 mg of fluvastatin alone, 8 g or 16 g of cholestyramine alone, or combinations of these fluvastatin and cholestyramine dosages (six treatment groups). MEASUREMENTS: Changes in lipid variables, particularly LDL cholesterol. RESULTS: The 10-mg and 20-mg fluvastatin monotherapy groups showed considerable reductions in LDL cholesterol initially (-20.1% [SD, 8.8%] and -20.2% [SD, 10.1%], respectively); these reductions were maintained. Reductions in LDL cholesterol that resulted from the addition of cholestyramine, 8 g/d, to 10 mg of fluvastatin and 20 mg of fluvastatin were greater than those observed with monotherapy (10-mg fluvastatin--[10-mg fluvastatin plus cholestyramine], 9.1%; 95% CI, 3.8% to 14.4%) and 20-mg fluvastatin--[20-mg fluvastatin plus cholestyramine], 11.6%; CI, 6.5% to 16.8%). The increase in cholestyramine dose to 16 g/d in the three combination groups provided only a modest additional response. CONCLUSIONS: Low-density lipoprotein cholesterol reductions of about 25% to 30% can be achieved with low-dose combination therapy with fluvastatin and cholestyramine. The addition of low-dose resin appears to produce greater overall cholesterol reduction than does a simple doubling of the fluvastatin dosage. The low-dose combination treatment was highly successful in achieving the goals of the National Cholesterol Education Program guidelines.

Anticholesteremic Agents↗
PubMed1994

Amlodipine versus atenolol in essential hypertension.

The efficacy and safety of amlodipine (2.5-10 mg) once daily was compared with atenolol (50-100 mg) once daily in patients with mild-to-moderate essential hypertension in a randomized, double-blind, parallel, placebo-controlled study. A total of 125 patients were randomly allocated at the end of a 4-week run-in placebo period to 8 weeks of double-blind treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The placebo group had small mean changes in supine and standing blood pressure compared with baseline. The mean blood pressure changes from baseline 24 hours postdose in the amlodipine group (mean daily dose 8.8 mg) were -12.8/-10.1 mm Hg for supine blood pressure and -11.5/-9.8 mm Hg for standing blood pressure (p < 0.001 compared with placebo), and for the atenolol group (mean daily dose 83.7 mg) the changes were -11.3/-11.7 mm Hg for supine blood pressure and -13.3/-12.3 mm Hg for standing blood pressure (p < 0.001 compared with placebo). There were no statistically significant blood pressure differences between active treatments. The responder rates for amlodipine, atenolol, and placebo were 61.1, 64.9, and 11.1%, respectively. The blood pressure values taken over the 24-hour period at final visit revealed that amlodipine and atenolol maintained the supine blood pressure < or = 140/90 mm Hg throughout the period of observation; the corresponding time-effect curve for the placebo group was clearly in the hypertensive range. Both amlodipine and atenolol were well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Medium-induced fragility of Schwanniomyces.

Schwanniomyces occidentalis has attracted interest because of its ability to metabolize starch and similar complex carbohydrates. Studies have been undertaken, mostly using defined media, to ascertain conditions for optimal production and secretion of hydrolytic enzymes. Here we demonstrate the fragility of Schw. occidentalis in many defined media. We especially examined viability in YNB (Yeast Nitrogen Base) plus 1% glucose. Without phosphate supplementation, viability was routinely very low at stationary phase (usually less than 37%), whereas viability of stationary-phase cultures in phosphate-supplemented YNB usually exceeded 97%. The negative implications of having many, presumably permeabilized, dead cells present in assays for secretion of enzymes by living yeast cells are discussed.

Culture Media↗
PubMed1993

Thromboxane and prostacyclin synthesis in experimental pancreas transplantation. Changes in parenchymal and vascular prostanoids.

The principal causes of failure of a pancreas transplant are rejection and vascular thrombosis. There is an unusually high attrition rate for pancreas transplants, but study models have been difficult to develop. In a rat model that allows study of acute rejection to the exclusion of nonspecific effects of transplant surgery on the pancreas, in vitro synthesis of prostacyclin (PGI2) and thromboxane A2 (TXA2) by transplanted pancreas and the blood vessels transplanted with it was measured using an RIA for their stable hydrolysis products 6-keto-prostaglandin F1 alpha and thromboxane B2 (TXB2). TXB2 synthesis was significantly greater in allotransplanted pancreas than isotransplanted pancreas from the 5th day after transplantation. Rejection was complete in the allografted group 7-9 days after transplantation. 6-Keto-prostaglandin F1 alpha synthesis was similar in the pancreas for both allografts and isografts. Similar changes were seen in aorta, celiac artery, superior mesenteric artery, and portal vein transplanted with the pancreas. In the transplanted aorta, TXB2 was significantly greater in the allograft group from the third posttransplant day. A group of CsA-treated allografts sampled after 9 days had transplanted pancreatic parenchymal and vascular prostanoid synthesis in the isograft range. The changes in PGI2 and TXA2 synthesis that accompany cellular rejection may mediate vascular failure in rejecting pancreas transplants, and changes in PGI2 and TXA2 synthesis in blood vessels transplanted with the pancreas could promote early vascular thrombosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Percutaneous transluminal angioplasty in transplant renal arterial stenoses: a long-term follow-up.

Transplant renal artery stenosis is a potentially treatable cause of post-transplant hypertension. Transluminal angioplasty under radiological control facilitates treatment, and in this study the results of 15 consecutive patients treated in one department have been analysed to assess the safety and success of the technique, blood pressure control and transplant function. Technical success was achieved in 14 patients (93%), with zero mortality and only 1 major complication requiring surgical intervention. Blood pressure control was significantly improved by angioplasty, mean blood pressure (diastolic + 1/3 pulse pressure) being lower 4-6 weeks later (P less than 0.05) and a mean of 34 months later (P less than 0.01), and transplant renal function was unaffected. In the treatment of transplant renal artery stenosis percutaneous transluminal angioplasty is effective, safe and often of lasting benefit.

Adolescent↗
PubMed1992

Micellar catalysis in flow injection systems: the nitrosation reaction.

The use of aqueous micellar carrier streams in flow injection is shown to catalyse on-line reactions and thereby improve the sensitivity relative to non-micellar systems. The effect of several different micellar systems on the nitrosation reaction of N,N-diethylaniline in acidic solution was investigated. The mechanism of the micellar enhancement is discussed and the sensitivities of the method in both aqueous and micellar media are compared. The presence of the cationic surfactant, cetyltrimethylammonium bromide, is shown to improve the sensitivity of the analysis. The effect of the micellar solution on the dispersion characteristics of the system was also studied. The greater viscosity of the micellar phase increases dispersion for non-reacting systems, but when monitoring a reaction product the increased reaction rate can counteract this and the micellar carrier can show less over-all dispersion than the aqueous carrier.

Catalysis↗
PubMed1992

A randomized, placebo-controlled, double-blind comparison of amlodipine and atenolol in patients with essential hypertension.

The efficacy and safety of amlodipine (2.5 mg, 5 mg, or 10 mg) once daily was compared with atenolol (50 mg to 100 mg) once daily in patients with mild-to-moderate essential hypertension in a randomized, double-blind, parallel, placebo-controlled study. One hundred and twenty-five patients were randomly allocated at the end of a 4-week run-in placebo period to 8 weeks' double-blind treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The mean changes from baseline in blood pressure 24 h postdose for amlodipine (mean daily dose 8.8 mg) were -12.8/-10.1 mm Hg for supine and -11.5/-9.8 mm Hg for standing blood pressure (P < .001). For atenolol (mean daily dose 83.7 mg) the changes were -11.3/-11.7 mm Hg for supine and -13.3/-12.3 mm Hg for standing blood pressure (P < .001). There were no statistically significant differences between treatments. The responder rates for amlodipine, atenolol, and placebo were 61.1%, 64.9%, and 11.1%, respectively. Determinations taken over the 24-h period at the final visit revealed that amlodipine and atenolol maintained the group mean supine blood pressure at or below 140/90 mm Hg throughout the period of observation; the corresponding time-effect curve for the placebo group was clearly in the hypertensive range. Heart rate was significantly lowered by atenolol only. Both amlodipine and atenolol were well-tolerated. Only one patient was withdrawn because of the development of peripheral edema, arthralgia, and fatigue after treatment with amlodipine. This study demonstrates that once-daily administration of amlodipine or atenolol to mild-to-moderate hypertensive patients was well-tolerated and provided adequate blood pressure control throughout the 24-h dosing interval.

Adolescent↗
PubMed1992

Morphology of rejection in experimental pancreas transplantation and its modification by cyclosporin A administration.

Histology of pancreas transplant rejection is complicated by non-specific appearances related to undrained exocrine secretions. Using a rat model of pancreas transplantation with exocrine drainage into the urinary tract, morphology of acute rejection has been studied with minimal interference from non-specific change. Unmodified acute rejection was complete after 7-9 days. Intralobular lymphocytic infiltration, which differentiated allografts from isografts, was present 5 days after transplantation and lymphocytic infiltration of islets and blood vessel walls developed between 5th and 7th days. Cyclosporin A immunosuppression of allografts resulted in marked attenuation of the cellular infiltrate. The nature of the infiltrate and its suppression with cyclosporin A indicated an allograft reaction.

Acute Disease↗
PubMed1991

Digoxin pharmacokinetics and spirapril, a new ace inhibitor.

As concurrent use of digoxin with the novel ACE inhibitor spirapril should be common, potential for spirapril to affect steady-state digoxin kinetics was studied. Fifteen healthy white male volunteers aged 22-42 and weighing 135-225 lbs took digoxin tablets 0.25 mg every 12 hours for 5 weeks. In crossover design, each also received spirapril or matching placebo capsules during weeks 1 and 2, or 4 and 5. Dosage of spirapril was increased from 12 mg to 48 mg once daily. Spirapril produced no significant effect on mean (+/- SD) serum digoxin concentration in the steady state, area under curve for 12 hours, peak digoxin level, time to peak, or urinary digoxin excretion over 12 hours. No change in renal or whole body digoxin clearance was seen. Unlike some other cardiovascular drugs, spirapril does not alter steady-state digoxin kinetics in healthy adults.

Administration, Oral↗
PubMed1991

Variability in psychometric test scores: the importance of the practice effect in patient study design.

1. Practice effect was determined for six types of psychometric tests given on eight occasions. 2. No plateau occurred. Stepwise mean decrease in Choice Reaction Time, Short Term Memory Errors, and Card Sorting Time, and stepwise mean increase in Mathematical, Visual Vigilance, and Digit-Symbol Substitution scores developed progressively. 3. Pre-trial training will usually fail to prevent practice effect from confounding effect of any intervention. 4. Design of drug intervention studies must take account of the continuing practice effect.

Adult↗
PubMed1991

A multicenter comparison of the safety and efficacy of isradipine and enalapril in the treatment of hypertension.

This multicenter trial compared the efficacy and safety of isradipine and enalapril in 160 patients with essential hypertension. Patients received isradipine or enalapril for 10 weeks after a placebo wash-out period of three to five weeks. Dosage was titrated for six weeks on the basis of blood pressure (BP) response and was then maintained for the remainder of the study. Isradipine reduced systolic and diastolic BP by 12 and 9 mm Hg, respectively, and enalapril by 10 and 7 mm Hg, respectively (between-treatment difference P less than .05 for diastolic BP). Overall, isradipine resulted in a higher responder rate, particularly among patients who had higher entry BPs. Fifteen enalapril-treated patients and four isradipine-treated patients discontinued treatment (four taking enalapril and none taking isradipine withdrew because of lack of efficacy). The most frequently reported adverse reactions were headache, dizziness, and edema in the isradipine group, and cough, headache, and chest pain in the enalapril group. Both drugs produced significant reductions in BP, but, in this study isradipine was more effective. The drugs were similarly well tolerated.

Adult↗
PubMed1991

Natriuresis secondary to carotid chemoreceptor stimulation with almitrine bismesylate in the rat: the effect on kidney function and the response to renal denervation and deficiency of antidiuretic hormone.

Almitrine bismesylate simulates the effects of arterial hypoxia in producing a specific and long-lasting excitation of the peripheral arterial chemoreceptors. Previous work has shown that almitrine produces a diuresis and natriuresis when given intravenously to anaesthetised rats in a stable mannitol induced diuresis. This response is abolished by glossopharyngeal nerve section implying that it is afferently mediated via the carotid body chemoreceptors. We have studied further the efferent limb of this response. The diuresis and natriuresis occurs without significant detectable changes in effective renal plasma flow and glomerular filtration rate suggesting that it is produced mainly by inhibition of renal tubular sodium and water reabsorption. Almitrine produces a diuresis and natriuresis in rats after bilateral nephrectomy and transplantation of a kidney from a donor rat. This effect is not therefore efferently mediated by the renal nerves and probably involves a humoral agent. Almitrine produces a diuresis and natriuresis in rats after bilateral adrenalectomy and in rats with congenital hypothalamic diabetes insipidus indicating that neither adrenal hormones nor changes in antidiuretic hormone levels are implicated.

Almitrine↗