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Biomedical subjects

E Johnson

Publications and source records attributed to E Johnson.

At least 307 records · Page 17Linked to original sources

Effects of fixation stiffness on fracture healing. External fixation of tibial osteotomy in the rabbit.

In rabbit tibial osteotomies, the effects on bone healing of three different degrees of stiffness of external fixation were investigated. Redislocation occurred in one third of the osteotomies with the least rigid fixation, and the amount of external callus was greater in this group. At 6 weeks there were no significant differences between the groups regarding bending strength and stiffness of the bones.

Animals↗

Bile salts as endogenous digitalis like factors.

Digitalis-like factors were assayed by radioimmunoassay of digoxin in 6 bile samples obtained from patients at autopsy and in plasma from three patients with combined hepatic and acute renal failure. None of the patients received digoxin. Digitalis like factor values in bile samples were 23 to 85 nmol digoxin equivalents/1. Bile salt concentrations ranged from 38-104 mmol/l in the bile and 28-184 mumol/l in the plasma of these subjects. Bile, plasma digitalis like factor extracts and bile salt standards (0.1-3 mM) showed concentration dependent displacement of [125I]-digoxin from digoxin antibody, inhibition of hog brain Na,K-ATPase and displacement of [3H]-ouabain from Na,K-ATPase. The concentration-displacement curves suggest that bile salts could account for 50-79% of the total digitalis like factors in the six bile samples and 2-7% in the plasma of the three patients. High performance liquid chromatographic fractionation of a bile sample showed digitalis like factor peaks co-eluating with standards of tauro- and glycocholate, tauro- and glycochenodeoxycholate and tauro- and glycodeoxycholate. These bile salt peaks accounted for 78% of the total digitalis like factors in all high performance liquid chromatographic peaks in bile, but only 7% of the total digitalis like factor activity in all high performance liquid chromatographic peaks in an extract of plasma from one of the patients with hepatic and renal failure. The bile salts appear to be examples of endogenous digitalis like compounds which do not act by simple competitive ligand binding to antidigoxin antibody and Na,K-ATPase. They make an important contribution to digitalis like factor activity in bile, but not in plasma.

Acute Kidney Injury↗

Failure of sodium bicarbonate to improve resuscitation from ventricular fibrillation in dogs.

To determine the value of sodium bicarbonate in resuscitation from ventricular fibrillation and the prevention of spontaneous refibrillation, sodium bicarbonate (1 meq/kg) or placebo was administered on a random basis to 16 pentobarbital-anesthetized dogs 18 min after the induction of ventricular fibrillation and cardiopulmonary resuscitation. Defibrillation was attempted 2 min after the administration of bicarbonate or placebo. All animals were successfully defibrillated, but three of eight bicarbonate-treated and two of eight control animals died in electromechanical dissociation (p = NS). Spontaneous refibrillation occurred in three animals in each group (p = NS). Successful resuscitation was not dependent on treatment, arterial or mixed venous Pco2, or arterial or mixed venous pH but correlated strongly with coronary perfusion pressure (p less than .003). Spontaneous refibrillation occurred without relation to any identifiable variable. The gradient between diastolic aortic and right atrial pressures was 24 +/- 2 mm Hg in controls and 23 +/- 2 mm Hg in treated animals over the entire 20 min of cardiopulmonary resuscitation (p = NS). However, among animals successfully resuscitated, mean diastolic coronary perfusion pressure averaged 27 +/- 2 mm Hg compared with 20 +/- 1 mm Hg among those dying in electromechanical dissociation (p less than .02). For the final 2 min of resuscitation, after drug administration, these gradients were 31 +/- 2 and 23 +/- 2 mm Hg, respectively (p less than .01). Microsphere determined myocardial perfusion correlated with the diastolic aortic-right atrial perfusion pressure gradient (r = .86) and was 0.43 +/- 0.03 ml/min/g in survivors and 0.22 +/- 0.01 ml/min/g in nonsurvivors (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Multiple daily fractionated radiation therapy and misonidazole in the management of malignant astrocytoma. A preliminary report.

Various attempts have been made to improve the effectiveness of radiation in the treatment of cerebral malignant astrocytomas. A trend favoring multiple daily fractionated (MDF) radiation therapy over conventional single daily fractionated (CF) radiation therapy was identified in our previous study. In order to assess the effect of MDF with and without misonidazole, a province-wide prospective randomized trial was initiated in January 1981. By March 1984, 124 patients with histologically verified grade III and IV astrocytomas were randomized to CF (5800 cGy/6 weeks/30 fractions), MDF (6141 cGy/4.5 weeks/69 fractions at 89 cGy every 3-4 hours, three times a day) and MDF in combination with misonidazole (1.25 g/m2 three times weekly for the first 3 weeks). Thirty-eight patients were randomized to CF, 43 patients to MDF, and 43 patients to MDF and misonidazole. At the preliminary assessment in July 1984, the median survival time was 27 weeks for the CF group, 39 weeks for the MDF group and 49 weeks for MDF and misonidazole group. The 1-year actuarial survival rate from surgery was 20% for CF group, 41% for MDF group, and 45% for MDF and misonidazole group. There is a statistically significant difference (P less than 0.001) between the CF and MDF group. However, the addition of misonidazole does not significantly alter survival.

Adolescent↗

Effect of ouabain on amino acid uptake by mouse ascites-tumour cells in the presence of nigericin.

Mouse ascites-tumour cells oxidizing lactate, in a modified Ringer solution, concentrated 2-aminoisobutyrate, L-methionine or 2-(methylamino)isobutyrate about 20-fold from a 0.4 mM solution in the presence of 2-3 micrograms of nigericin/mg cellular dry wt. The ionophore increased cellular [Na+] to almost 100 mM when extracellular [Na+] was about 45 mM. Either valinomycin or the two mitochondrial inhibitors oligomycin and antimycin acting together each markedly lowered the extent to which the tumour cells concentrated amino acid, from the above factor of about 20 to roughly 2-fold. Ouabain (1 mM) had a similar effect, and further raised cellular [Na+]. The sodium pump appeared to be closely involved in amino acid uptake under these conditions.

Amino Acids↗

Comparison of the distribution and binding of monoclonal antibodies labeled with 131-iodine or 111-indium.

The distribution of two monoclonal antibodies with reactivity against human leukemia/lymphoma associated antigens (BA-1 antibody) and carcinoembryonic antigen (202 antibody) when labeled with 131I or 111In was studied in normal Balb/c mice. The BA-1 antibody of the IgM subclass was labeled with 131I by the micro iodine monochloride method at a 12:1 molar ratio and with 111In by the cyclic DTPA anhydride method at a 10:1 molar ratio. In vitro, the 131I-labeled BA-1 antibody bound 35.5% to 10(7) KM-3 leukemic cells while the 111In-labeled BA-1 antibody bound 29.9% to the same number of KM-3 cells. In vivo, the 111In-labeled BA-1 antibody showed a higher accumulation in liver, spleen, and kidney than the 131I-labeled BA-1 antibody. The 202 antibody of the IgG1 subclass was labeled with 131I at a 5:1 molar ratio and with 111In at a 7:1 molar ratio. In vitro, the 131I-labeled 202 antibody bound 30.9%, 27.4%, and 30.0% to 10(7) CO-112, WIDR, and LS-174T colon cancer cells, respectively. The 111In-labeled 202 antibody bound 20.5%, 30.2%, and 33.6%, respectively to the same number of colon cancer cells. In vivo, the 131I-labeled 202 antibody showed a higher tissue to blood ratio in liver, spleen, and kidney than the 111In-labeled 202 antibody. The data indicate that the relative distribution of 131I-labeled versus 111In-labeled monoclonal antibody may depend on the immunoglobulin subclass of the antibody and the molar ratio used in labeling.

Animals↗

Seasonal changes in the testes and accessory reproductive organs and seasonal and circadian changes in plasma testosterone concentrations in the male grey squirrel (Sciurus carolinensis).

A 27-month study of cycles of regression and recrudescence of testis function in adult, grey squirrels in a natural environment in southern England has shown concomitant variation in mean testes weights, mean plasma testosterone concentrations, and mean weights of accessory sex organs, this variation being closely associated with months of the year. Testis regression occurred in the period June to August, the exact timing differing among individuals. In 1979-1980 the testes of all squirrels then remained regressed for 7 months, whereas in the autumn of 1980 testes were regressed in most squirrels for 4 months. There was also evidence of testis regression in some individuals in March 1979 and March 1981. Males born and housed in a small woodland enclosure in 1979-1980 and well fed with grain did not experience the long period of regressed testes. Plasma testosterone concentrations measured hourly over 24 hr in squirrels with large, active testes varied from 0.4 to 20 nmol/l, both within and between individuals, the higher concentrations being observed between midday and midnight. The range in the age of males at puberty, based on fusion of the epiphyses of the wrist, was 1.0 to 1.25 year. Juvenile males housed in a woodland enclosure together with adult males and females remained prepubertal up to 2 years of age.

Animals↗

Fibronectin binds to complement-coated agarose beads and increases their association to mouse macrophages.

We have studied the binding of fibronectin to complement (C3b, C3bi, C3d)-coated agarose beads and its effect on cell association of such beads to mouse macrophages. Fibronectin bound to agarose beads preincubated in human serum, whereas no binding occurred after preincubation of the beads with complement-inactivated (50 degrees C for 20 min or ethylenediaminetetraacetic acid) sera. The binding of iodine-labelled fibronectin to beads preincubated in fibronectin-depleted serum (HS-FIB) was about twice that of beads preincubated in normal serum. Unlabelled fibronectin inhibited the following binding of labelled fibronectin to beads pretreated in HS-FIB. A similar amount of fibronectin bound to agarose beads coated with equimolar amounts of C3b, C3bi, or C3d, suggesting that the common domain C3d carries the main binding site(s) for fibronectin. Preincubation of serum-treated and trypsinized agarose beads with fibronectin led to an increased association (22%) of such beads to mouse macrophages. The results indicate that fibronectin promotes binding of complement-coated agarose beads to mouse macrophages, whereas the ingestion of the beads is mediated via complement C3 receptors.

Animals↗

Skeletal muscle basement membrane in maturity-onset diabetes in the young.

We have studied skeletal muscle capillary basement membrane width (CBMW) and intensity of skeletal muscle extracellular basement membrane staining for albumin and IgG in eight families with maturity-onset diabetes in the young (MODY). Ninety-two MODY patients were identified. Sixty-three of these patients, 33 relatives with nondiagnostic oral glucose tolerance studies, and 61 normoglycemic relatives were studied for glucose and insulin. Twenty-six of these MODY patients, 20 normoglycemic relatives, and 16 unrelated normal controls had skeletal muscle capillary morphologic studies. The muscle capillary basement membrane was significantly increased in MODY patients younger than 40 yr when compared with unrelated normal subjects and relatives of the same age (P less than 0.001). However, in these families, the CBMW of MODY patients showed no significant thickening with age (slope = 0.45, P less than 0.14), as expected and seen in the normal subjects and in the normoglycemic relatives of the patients (slope = 1.21, P less than 0.001). The slope derived from the linear regression of age and CBMW in MODY patients (0.45 +/- 0.29) was significantly less (P less than 0.05) than that of the nondiabetic subjects (1.21 +/- 0.19). The mean intensity of skeletal muscle extracellular basement membrane staining for albumin was higher in MODY patients (1.1 +/- 0.15) than in unrelated normal subjects (0.7 +/- 0.1, P less than 0.025) and normal MODY family members (0.6 +/- 0.08, P less than 0.01). The unexpected absence of basement membrane thickening with age in the MODY patients may explain the paucity of vascular complications that have been reported by some.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Dehydroepiandrosterone sulfate as a digitalis like factor in plasma of healthy human adults.

Plasma values for digitalis like factors (DLF) and dehydroepiandrosterone sulfate (DHEA-S) in 11 healthy adults were (mean +/- SD) 44 +/- 6 pmol digoxin equivalents/L and 11 +/- 3 mumol/L respectively. DHEA-S accounted for 62-100% of the total plasma DLF. DHEA-S and plasma DLF displaced [125I]digoxin from digoxin antibody, inhibited hog brain Na,K-ATPase and displaced [3H]ouabain from ATPase in a concentration dependent manner similar to digoxin. Plasma extracts (11 subjects) inhibited Na,K-ATPase and displaced [3H]ouabain from Na,K-ATPase with mean values +/- SD of 1.7 +/- 0.22 and 1.8 +/- 0.25 nmol digoxin equivalents/L plasma respectively. HPLC fractionation of plasma DLF showed several peaks. The major peak was due to DHEA-S, identified by its retention time, radioimmunoassay of DHEA-S and mass spectrometry.

Adult↗

Anterior thigh pain or tenderness. A diagnostically useful manifestation of bacteremia.

In four patients with putative infectious process, anterior, bilateral proximal thigh pain and tenderness unaccompanied by generalized myalgias developed. This unusual manifestation, observed in these and other patients, was associated with demonstrable bacteremia. Aside from tenderness, no local abnormalities were found and the pain and tenderness disappeared after appropriate therapy. Creatine kinase levels, measured in three of the four patients, were elevated in only one. This manifestation is useful clinically as it strongly suggests bacteremia; attention to this finding can be lifesaving.

Abdomen↗

Salmonella infections in patients with acquired immunodeficiency syndrome.

Salmonella infections occurred in six patients with acquired immunodeficiency syndrome (AIDS) and one patient with probable AIDS. The immune system defects increase the susceptibility of patients with AIDS to salmonella infections. Recognition of salmonellosis in patients with AIDS is important because of a high propensity of this organism to invade the bloodstreams of these patients, and because, unlike other infections in patients with AIDS, this infection can be easily treated.

Acquired Immunodeficiency Syndrome↗

Early changes in plasma and urinary potassium in diuretic-treated patients with systemic hypertension.

Two groups of patients with uncomplicated systemic hypertension were studied. Group 1 included 11 patients who had overt hypokalemia with diuretic drug treatment, and group 2 included 11 patients who remained normokalemic. After baseline studies without treatment were performed, both groups received hydrochlorothiazide, 50 mg twice daily. Plasma potassium (PK) was significantly reduced within the first day of treatment and stabilized by day 7 in both groups. The average decrease in PK was 1.0 +/- 0.1 mEq/liter (p less than 0.01) in the first group and 0.6 +/- 0.2 mEq/liter (p less than 0.01) in the second group. Cumulative losses of K were approximately 200 mEq in the hypokalemic group and were minimal in the normokalemic group as assessed by 24-hour urinary collections. Patients in the hypokalemic group also had a greater reduction in body weight and blood pressure. Supplementation with KCl, 96 mEq/day, or triamterene, 200 mg/day, in 9 hypokalemic patients resulted in an increase of PK to approximately 3.5 mEq/liter leveling off by day 7, and a cumulative K retention of approximately 200 mEq. Thus, overt thiazide-induced hypokalemia was associated with small and biologically unimportant losses of K from body stores. With replacement therapy the estimated amount of retained K was also small.

Blood Pressure↗

Lysosomal glycosidases in mouse peritoneal macrophages stimulated in vitro with soluble and insoluble glycans.

Mouse peritoneal macrophages stimulated with insoluble glycans in vitro release high amounts of acid hydrolases, N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, and beta-D-galactosidase. The most potent of the stimulatory glycans is a beta-1,3-D-glucan isolated from yeast cell walls. Up to 50% of total enzyme activity was found in the medium after stimulation with this glycan for three days. Agarose, another insoluble glycan containing an alternating sequence of the disaccharide beta-1,3-D-galactose-alpha-1,4-3,6-anhydro-L-galactose units was less potent. The soluble beta-1,3-D-glucan laminaran, which also contains small amounts of mannitol, was not able to induce release of acid glycosidases from macrophages. The release was independent of serum since macrophages cultured under serum-free conditions showed nearly the same pattern of enzyme activities, both in the cells and media. There was no increased release of the acid hydrolase alpha-D-mannosidase after stimulation with the insoluble beta-1,3-D-glucan for three days. The release of the lysosomal glycosidases was not due to cell death, since only small amounts of the cytoplasmic enzyme lactate dehydrogenase were found in the culture media. Insoluble polystyrene latex particles were not able to stimulate mouse macrophages to release lysosomal glycosidases. Tritiated glycans (amylose, dextran, laminaran, the insoluble beta-1,3-D-glucan, and agarose) and the p-nitrophenyl-glycopyranoside derivatives were used as substrates to investigate whether the macrophages contained or released glucanases capable of degrading alpha-1,4-D-glucans, alpha-1-6-D-glucans, beta-1,3-D-glucans, and agarose respectively. We conclude that the glycans were not degraded in macrophage cultures during the time period tested nor were the enzymes induced in macrophages by the glycans during in vitro culture for seven days.

Animals↗