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Biomedical subjects

A Lev-Ran

Publications and source records attributed to A Lev-Ran.

At least 19 recordsLinked to original sources
PubMed1992

Release of different fractions of epidermal growth factor from human platelets in vitro: preferential release of 140 kDa fraction.

Platelet-rich plasma in acidic-citrate-dextrose anticoagulant was kept for 5 days in an oxygen-permeable bag at 22 degrees C in an incubator/rotator. Platelet count remained stable throughout the experiment. On days 0, 3 and 5, aliquots were removed; platelets were isolated by centrifugation at 22 degrees C, 1500 g for 20 min, reconstituted to the original volume with PBS buffer, and the contents of alpha-granules were released by repeated freezing and thawing. Epidermal growth factor (EGF) and beta-thromboglobulin (beta-TG) in the platelet-poor plasma and platelet lysates were determined by radioimmunoassays. Results indicated that in platelet-free plasma, both total EGF and beta-TG increased 3-5-fold after 5 days; this amount represented 10-20% of the factors stored in the platelets. Correspondingly, the EGF and beta-TG contents of the platelet lysates exhibited accompanying decreases. HPLC fractionation showed that the main EGF fraction which progressively decreased in the lysates and increased in plasma had a molecular mass of 140 kDa. The contents of the 67 kDa and 6 kDa fractions did not change substantially. We conclude that under these conditions, the 140 kDa fraction was released preferentially. In view of these and previous experiments, it seems likely that different organs contribute to plasma EGF fractions.

Adolescent↗
PubMed1992

Effects of platelet-contained growth factors (PDGF, EGF, IGF-I, and TGF-beta) on DNA synthesis in porcine aortic smooth muscle cells in culture.

Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and transforming growth factor-beta (TGF-beta) are potent mitogens present in human platelets. Since they are likely to be released simultaneously at the site of vessel injury, their combined effects on vascular smooth muscle cells are more relevant physiologically than their individual actions. Therefore, we added various concentrations of growth factors to quiescent porcine aortic smooth muscle cells cultured in low-serum (0.5%) medium and measured the amount of [3H]thymidine incorporated into DNA. Effect of TGF-beta alone was concentration-dependent: stimulatory (1.5-fold increase over the basal) at 0.025 ng/ml and inhibitory at greater than or equal to 0.1 ng/ml. Effects of the other three growth factors on DNA synthesis were only stimulatory; their maximally effective concentrations were 20 ng/ml for PDGF (eightfold over the basal), 40 ng/ml for EGF (six-fold increase), and 20 ng/ml for IGF-I (fourfold increase). When PDGF, EGF, and IGF-I were added at submaximally effective concentrations, their effects were additive. TGF-beta at 1 ng/ml inhibited at least 50% of the effects of 20 ng/ml EGF and of 10 ng/ml IGF-I, whereas inhibition of the effect of 10 ng/ml PDGF required 10 ng/ml of TGF-beta. The concentration of TGF-beta needed to inhibit 50% of the combined effect of EGF, IGF-1, and PDGF was 5 ng/ml. These results show complex interrelationships between the growth factors contained in the alpha-granules of human platelets in their effects on porcine aortic smooth muscle cells.

Animals↗
PubMed1992

Origin of urinary epidermal growth factor in humans: excretion of endogenous EGF and infused [131I]-human EGF and kidney histochemistry.

1. This study examined (i) whether blood-infused epidermal growth factor (EGF) can pass into urine; (ii) whether infused labelled EGF behaves like endogenous plasma immunoreactive EGF; and (iii) which parts of the human nephron show morphological evidence of EGF synthesis? 2. We infused human [131I]-EGF into a volunteer. After 6 min, only 66% of the plasma counts represented intact EGF. At the end of infusion, the T1/2 of EGF was calculated to be 1.6 min. The tail of the curve lasted for at least another 2 h. The total excretion of the labelled EGF was 2.45% of the infused dose and was proportional to the urine volume. 3. After a water load, the excretion of endogenous EGF was, on the contrary, inversely related to urine volume. 4. Immunohistochemically, human kidneys were not stained by monoclonal anti-EGF antibodies but showed positive in situ hybridization for EGF mRNA in the nuclei of glomerular mesangial cells, distal convoluted tubules and collecting tubules. 5. We conclude that human kidneys synthesize EGF and release it into urine. Plasma-derived EGF constitutes under normal conditions only a small part of the urinary EGF. Contrasting volume-dependency of the excretion of endogenous and [131I]-EGF requires further study and cautions against extrapolating results obtained with labelled EGF to physiological conditions.

Epidermal Growth Factor↗
PubMed1991

Trauma, especially of the submandibular glands, causes release of epidermal growth factor into bloodstream in mice.

Submandibular glands in mice were traumatized by handling and then removed. Immunoreactive epidermal growth factor (EGF) in serum increased after 5 min and continued to increase, reaching at 1 h a peak of 50-fold normal in males and twice normal in females. If after traumatization the glands were repositioned with their blood supply intact, maximal increase of serum EGF at 1 h was 190-fold control values in males and 2-fold in females. In male mice, incision of abdominal wall skin led to a 15-fold increase of EGF in the serum; this rise was absent 3 days after sialoadenoectomy. After traumatization, repositioned submandibular glands lost 80% of their EGF; after the abdominal wall incision, only 30%. Following removal of submandibular glands, decrease of EGF level in serum was very slow: to 60% of the initial value after 3 days and to 40% after 10 days. By the HPLC characteristics, immunoreactive EGF in control serum and at its peak were indistinguishable. Urinary excretion of EGF was significantly elevated only when its serum level was 190-fold normal. We conclude that traumatized submandibular glands discharge into circulation a large part of their stored EGF. A similar but much less pronounced process takes place after abdominal skin incision. The presence of EGF in serum after its slow decline in sialoadenoectomized mice shows that a fraction of circulating EGF may recirculate prolonging its apparent half-life.

Animals↗
PubMed1991

Immunoreactive epidermal growth factor in serum, plasma, platelets, and urine in patients on chronic dialysis.

In 25 patients with chronic renal failure undergoing hemodialysis the level of epidermal growth factor (EGF) was significantly increased in plasma (61 +/- 10 vs. 36 +/- 12 pM in 23 aged-matched controls; p less than 0.0001) and serum (189 +/- 51 vs. 138 +/- 69 pM, p less than 0.006) and slightly increased in platelets (391 +/- 134 vs. 308 +/- 87 aM/10(6) platelets in controls; p less than 0.0582). In those 15 patients who produced urine, EGF was absent or close to the low limit of the sensitivity of the method (17 pM). Thus, kidneys are not delivering EGF to blood but their role in EGF removal is possible. Urinary EGF virtually disappears in severe chronic renal failure.

Aged↗
PubMed1990

Excretion of epidermal growth factor (EGF) in diabetes.

Excretion of epidermal growth factor (EGF) is decreased in renal failure. We assayed it in diabetes mellitus in an attempt to relate it to clinical parameters, esp. those of diabetic nephropathy. EGF excretion declined with age but in all age groups of diabetic patients was below the first percentile for controls. In 26 control and 34 prepubertal diabetic children excretion was correspondingly 1126 +/- 442 and 932 +/- 489 pmol/mmol creatinine (P = 0.087); in 26 control and 42 diabetic adolescents below age 18, 778 +/- 222 and 676 +/- 335 (P = 0.023) and in 81 control and 83 diabetic adults, 371 +/- 153 and 235 +/- 140 (P less than 0.0001). Decreased excretion of EGF was seen in some patients without any diabetic complications. Excretion of EGF was independently and inversely correlated with age and duration of diabetes but not with type of diabetes, treatment, body built, C-peptide, plasma glucose, glycohemoglobin or retinopathy. A positive correlation was seen with creatinine clearance and a negative correlation, with albuminuria, but the strongest and the only independent correlation found by stepwise multiple variable selection was with serum creatinine (r -0.711, P less than 0.0001). EGF excretion was not elevated in patients with hyperfiltration. We conclude that EGF excretion is abnormal in many patients with diabetes and that this abnormality reflects a kidney function different from glomerular filtration or glomerular permeability.

Adolescent↗
PubMed1990

Infusion of epidermal growth factor in mice: organ distribution and urinary excretion.

Anesthetized mice were infused into the tail vein with 7.5% mannitol in saline (0.1 ml/min for 60 min) alone or with EGF at 0.5 microgram/min. Urine was collected every 10 min starting 20 min after the beginning of the infusion and ending 20 min after its termination. EGF concentration in the serum of mice infused with EGF increased from the baseline level of 0.6 +/- 0.4 to 70.7 +/- 16.0 ng/ml at 80 min. Total excretion of EGF for 80 min was 117 +/- 49 ng with mannitol alone and 1916 +/- 420 ng (6.4% of the EGF infused) after mannitol with EGF. Serum and urine EGF was indistinguishable from the native mouse EGF by its radioimmunoassay and HPLC characteristics. Intact labeled EGF was also found in urine when mice were infused with 125I-EGF (1 x 10(6) cpm/ml) in mannitol. After 5 min infusion with 125I-EGF (6 x 10(6) cpm/ml in saline), more than 80% of the label was found in the liver and kidneys and more than 90% of it was intact EGF. However, 30 min after infusion more than 95% of the labeled EGF was degraded. We conclude that at least part of the urinary EGF in mice originates in blood and that liver and kidneys are the main organs of EGF degradation.

Animals↗
PubMed1990

Hepatotoxicity induced by diethylnitrosamine causes no significant disturbances of systemic glucose homeostasis in rats.

In rats, a moderately hepatotoxic single dose of diethylnitrosamine (DEN) 100 mg/kg causing depletion of liver glycogen, elevation of aspartate aminotransferase and decreased liver uptake of 3-O-methylglucose, resulted in substantial changes in insulin and glucagon balance. Two days after DEN, insulin binding to liver membranes and insulin removal by the liver were sharply reduced whereas its binding to muscle and adipocyte membranes remained unaltered. Serum insulin (random and after an overnight fast) remained normal. Intravenous (I.V.) insulin (10 U/kg) caused the usual degree of hypoglycemia that, however, lasted longer than in the control animals. Removal of glucagon by liver was also depressed in spite of its normal binding to hepatocytes, and peripheral serum glucagon was increased three-fold. I.V. glucagon (40 micrograms/kg) resulted in a blunted response of plasma glucose. I.V. glucose tolerance test (1 g/kg) remained normal in spite of the insulin increase to a level twice as high as in the controls, and in spite of nonsuppressed glucagon. These changes were still present after 1-3 months, but disappeared by 6 months. The results demonstrate remarkable ability of homeostatic mechanisms to preserve normal plasma glucose and glucose tolerance in spite of dramatic changes in insulin and glucagon.

Animals↗
PubMed1990

Epidermal growth factor and platelet-derived growth factor in blood in diabetes mellitus.

Epidermal and platelet-derived growth factors are potent mitogens for many types of cells, including smooth muscle cells. Epidermal growth factor in blood of humans is present both in platelets (as reflected in its serum level) and in plasma, the source(s) of which remains unknown. We assayed its level in 82 diabetic patients and 53 age-matched controls. In diabetes, epidermal growth factor level was increased in serum (191 +/- 43 vs 155 +/- 64 pmol/l, p = 0.0002) and plasma (53 +/- 9 vs 38 +/- 14 pmol/l, p less than 0.0001), without any difference between the patients with and without complications. Platelet-derived growth factor level was assayed only in serum of 19 patients with uncomplicated diabetes and found elevated (222 +/- 47) as compared with 13 controls (160 +/- 26 pmol/l), (p = 0.0002). Type of diabetes, its duration, mode of therapy, control, presence of retinopathy or albuminuria (in case of epidermal growth factor), as well as C-peptide age and sex did not correlate with epidermal or platelet-derived growth factor levels. Serum but not plasma epidermal and platelet-derived growth factor were negatively correlated with serum creatinine (correspondingly, r = -0.373, p = 0.0008 and r = -0.564, p = 0.0285). It is concluded that diabetes itself and not its complications cause increased levels of epidermal growth factor in plasma and serum and of platelet-derived growth factor in serum.

Adult↗
PubMed1990

Epidermal growth factor in blood and urine of athyreotic adults.

The total contribution of the thyroid to epidermal growth factor (EGF) levels in blood and urine was determined in 18 patients cured from thyroid cancer at the time of thyroxine treatment and 6 weeks off it in the state of athyroidism. As compared to the euthyroid state, the athyrodism was associated with a drop in the urinary EGF excretion from 24.8 +/- 8.4 to 11.8 +/- 4.6 ng/mg creatinine (p less than 0.0001) and some increase in the EGF level in blood serum from 159.5 +/- 55.0 to 191.2 +/- 41.0 pM (p = 0.023). We conclude that the thyroid affects the synthesis and/or blood delivery of EGF and is responsible for approximately one half of its urinary excretion.

Adult↗
PubMed1990

Megakaryocyte synthesis is the source of epidermal growth factor in human platelets.

Epidermal growth factor (EGF) is known to be present in the alpha granules of human platelets; however the source of this EGF, ie, whether it is taken up by the platelets from the circulation, or whether it is packaged into the platelets from the megakaryocyte during thrombopoiesis, is unknown. To determine whether EGF is taken up by platelets, platelets for EGF receptors were assayed and it was attempted to detect uptake of EGF by the platelets from culture medium. Platelets were found to lack EGF receptors, and no uptake of EGF from the culture medium was detected. To assess whether EGF is packaged into platelets from the megakaryocyte, megakaryocytes in frozen section bone marrow cores were stained for EGF protein by immunohistochemistry, and it was demonstrated that EGF is present in megakaryocytes. In addition, staining of megakaryocytes by in situ hybridization for EGF mRNA demonstrated its presence in these cells. Therefore it is concluded that the source of EGF in human platelets is the megakaryocyte and that this EGF is synthesized in the megakaryocyte rather than being taken up from its environment.

Base Sequence↗
PubMed1979

Glycohemoglobins and glucose tolerance.

Glycohemoglobin (GHb) levels were assayed after chromatography on weakly acidic acrylic cationite columns in 167 patients undergoing glucose tolerance test (GTT) and in 105 known diabetics. In 95% of patients with normal GTT levels, the GHb level was in the range of 6.8% to 9.8%. The GHb level was normal in patients with latent diabetes. Glycohemoglobin levels were elevated in patients with poorly controlled diabetes. Even in patients with normal GTT results, GHb levels correlated positively with fasting plasma glucose and glucose tolerance values. In patients with abnormal GTT results or diabetes but not receiving insulin therapy, the correlation between GHb levels and fasting plasma glucose values was significant. The GHb level that distinguished between latent and overt diabetes correlated strongly with the values of fasting plasma glucose and glucose tolerance and reflected changes in the control of diabetes.

Adult↗
PubMed1978

Clinical observation on brittle diabetes.

The brittleness of 100 severe diabetics was calculated as the mean of differences of blood glucose between two consecutive days at four time points (fasting, one and two hours after breakfast, and two hours after lunch). Mean daily difference (MDD) had a unimodal distribution; 15 patients with a MDD greater than 100 mg/100 ml were classified as most brittle. There was no correlation between MDD and insulin requirement. The brittle diabetics received 26 to 48 units of insulin/day. The insulin-resistant patients had low MDD values. No difference was found between seven patients with brittle diabetes and seven stable matched controls in insulin-binding capacity or total insulin. In two groups of six patients each with brittle diabetes, it was found that the stable dosage caused less brittleness than a sliding-scale regimen and that routine injection of 4 units of regular insulin before meals slightly decreased the mean diurnal glycemia level but increased the number of hypoglycemias. In two brittle diabetics, the blood glucose level was stabilized on intravenously administered insulin infusion, and in these patients, meals caused only a moderate hyperglycemia.

Adult↗
PubMed1977

Androgens, estrogens, and the ultimate height in XO gonadal dysgenesis.

We observed 40 patients with 45,X gonadal dysgenesis from the age of 13 to 15 years until the age of 18 to 21 years. The ultimate height of the 12 nontreated patients was 143.2 cm. Of 15 patients treated with nandrolone phenpropionate or methandrostenolone, the ultimate height was 143.3 cm, and of 13 patients treated with ethinyl estradiol, the height reached was 144.1 cm. The mean height of ten patients first seen at the age of 25 to 31 years was 140.1 cm. The mean height at any age was almost identical in all the groups. The growth velocity was somewhat accelerated by anabolic steroids and to a lesser extent, by estrogens only during the first year of therapy, and this did not influence the ultimate height. We saw no deleterious effects of the estrogens. In all the groups, there were patients who grew for some time at rates of up to 4 to 6 cm/yr. Therefore, long-term follow-up studies are needed for the evaluation of the effects of any treatment.

Adolescent↗
PubMed1977

Treatment of benign prostatic hyperplasia with hydroxyprogesterone-caproate: placebo-controlled study.

A placebo-controlled study with progesterone compound, 17-alpha-hydroxyprogesterone 17-n-caproate (Primostat), in 39 patients with benign enlargement of the prostate is reported. Statistical analysis of the results showed no evidence of significant improvement in patients receiving hydroxyprogesterone-caproate. No evidence of an effect as compared with the placebo was found when the residual urine, prostatic size, and histologic and ultrastructural changes of the removed prostatic gland in 6 of the patients, and in the luteinizing hormone, follicle-stimulating hormone, and estrogen urine levels in 21 patients were examined. Subjective effects, when carefully analyzed, provided some beneficial evidence, however not substantiated, when the patients' mode of voiding was carefully watched. The reported beneficial subjective improvement might be attributed to the enhancement of the beta-adrenergic response by the progesterone compound of the adrenergic receptors in the posterior urethra and bladder, presumably causing relaxation of its smooth muscle. The problems associated with the choice and measurement of parameters to be used in this type of investigation are discussed, and the absolute necessity of proper controls, statistical analysis, and close follow-up of the patients is pointed out.

Aged↗
PubMed1977

Brittle diabetes in pregnancy.

In eight brittle diabetics the insulin requirement increased during successful pregnancies from 35 to 64 U./day (in 29 stable severe diabetics from 53 to 78 U./day). The within-day glycemic excursions were calculated as the mean of the three differences between four time points: fasting, one hour after breakfast, two hours after breakfast, and two hours after lunch. This parameter was constant throughout the pregnancy in nondiabetics (34-46 mg./100 ml.) and stable severe diabetics (55-72 mg./100 ml.). In brittle diabetics it dropped from 147 mg./100 ml. before the pregnancy and 153 mg./ 100 ml. at eight weeks to 85 mg./100 ml. at 36 weeks. The between-day variability was calculated as the mean glycemic difference between two successive days at the four points of time noted above. It was very low in nondiabetics (49-53 mg./100 ml.). In brittle diabetics it decreased from 127 mg./100 ml. before pregnancy and 120 mg./100 ml. at eight weeks to 46-55 mg./100 ml. at 24-36 weeks. This shows that brittleness substantially decreased in the second half of pregnancy.

Adult↗