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Biomedical subjects

A L Mattila

Publications and source records attributed to A L Mattila.

6 recordsLinked to original sources

Human epidermal growth factor: renal production and absence from plasma.

Among the unsettled questions in the physiology of human epidermal growth factor (EGF) are (1) does EGF circulate in the blood and (2) what is the source of the abundant urinary immunoreactive EGF (irEGF). Therefore, we monitored the concentration of irEGF by an ultrasensitive assay in blood plasma from 5 healthy subjects every 20 min overnight carefully avoiding activation of platelets. Detectable levels (0.8-3.7 pM) were observed in only one of the subjects, in 5 of 29 samples. In random day-time plasma samples from 18 healthy adults, EGF was undetectable (less than 0.8 pM) in 13 subjects, and in 5 subjects EGF levels ranged from 2.2 to 4.9 pM. Furthermore, in 5 patients with a tumor in a functioning kidney we measured urinary relative irEGF concentration (nmol/mmol creatinine) before and after unilateral nephrectomy. The concentration fell by approximately 50%. Our findings are consistent with (1) blood irEGF residing exclusively in platelets, and (2) urinary irEGF originating from the kidneys.

Adolescent↗

Urinary epidermal growth factor concentrations in various human malignancies.

We determined the concentrations of immunoreactive epidermal growth factor in the urine (U-irEGF) of 97 adult patients with various malignancies, including carcinomas of the urinary bladder, kidney, stomach, colon, rectum, breast, endometrium, uterine cervix, ovary, vagina, prostate, pancreas and thyroid, liposarcoma and skin melanoma. The relative U-irEGF concentrations (ng m-1 creatinine) were higher (P = 0.002) for the whole series of female patients than for healthy controls matched for sex and age. Such difference did not appear for male patients. The only specific group with a statistically supranormal U-irEGF concentration (P = 0.0005) comprised women with endometrial carcinoma of the uterus.

Adult↗

Human epidermal growth factor concentrations in urine, but not in saliva and serum, depend on thyroid state.

To evaluate the effects of thyroid hormones on the concentration of epidermal growth factor (EGF), we determined values for the immunoreactive EGF concentration in the urine (U-irEGF) of newborn infants with congenital hypothyroidism (N = 19), and in urine, saliva and serum of adult patients with hypothyroidism (N = 11) and hyperthyroidism (N = 8). The values were expressed as SD score (SDS), i.e. deviation in SD units from their mean value of healthy subjects of the same age and sex. The SDS of relative U-irEGF (ng/mg creatinine) was lower (P less than 0.01) in newborn infants with congenital hypothyroidism (-0.8 +/- 0.2; mean +/- SEM) than in healthy infants. Their relative U-irEGF correlated with their serum T4 concentrations (r = 0.59, P less than 0.01). The SDS of relative U-irEGF was lower (P less than 0.01) in adult hypothyroid patients (-1.2 +/- 0.5) and higher (P greater than 0.05) in adult hypothyroid patients (0.9 +/- 0.6) than in healthy adult subjects. When subsequently euthyroid, their SDS of relative U-irEGF increased to -0.5 +/- 0.3 (P less than 0.01), and decreased to -0.7 +/- 1.1 (P less than 0.05), respectively. The irEGF concentrations in saliva and serum were not significantly different between the hypothyroid and hyperthyroid patients. Our results indicate that urinary excretion of irEGF in man is dependent on thyroid hormone.

Adult↗

Human urinary epidermal growth factor: effects of age, sex and female endocrine status.

Urinary concentrations of immunoreactive epidermal growth factor (irEGF) were determined by specific homologous radioimmunoassay in 300 healthy women and 163 healthy men between 16 and 93 years of age. Both absolute (ng/ml) and relative (ng/mg creatinine) concentrations decreased with age in both sexes. The relative concentration was higher in women than in men at ages 20-70 years (P less than 0.001), the respective mean values (ng/mg creatinine) being 49.1 and 40.1 at 16-20 years, 58.9 and 41.8 at 20-30 years, 47.6 and 36.9 at 30-45 years, 42.8 and 29.0 at 45-55 years, 44.9 and 30.1 at 55-70 years, and 16.0 and 18.5 in those over 70 years. The values were unaffected by the menstrual cycle, pregnancy, oral contraceptives, or postmenopausal estrogen and/or progestin therapy.

Adolescent↗

Subnormal concentrations of urinary epidermal growth factor in patients with kidney disease.

We determined the concentrations of immunoreactive epidermal growth factor (irEGF) and creatinine in urine samples from 47 adult patients with various kidney diseases and wide ranges of azotemia and proteinuria. In most of the patients, urinary irEGF concentrations (nanograms per mg creatinine) were markedly subnormal. In the entire group, urinary irEGF correlated with creatinine clearance (r = 0.79; P less than 0.001) and serum creatinine concentration (r = -0.85; P less than 0.001). In the subgroups of patients with primarily glomerular or tubulointerstitial diseases, similar correlations were found. By contrast, there was no correlation with proteinuria. We also determined the concentrations of plasma irEGF in five patients with azotemia. In four patients, the irEGF to creatinine concentration ratio was 1.9- to 8.9-fold higher in urine than in plasma, indicating that plasma irEGF was not the main source of urinary irEGF in these patients. Our data are compatible with the theory that urinary irEGF originates from nephrons per se.

Adolescent↗

Epidermal growth factor in human urine from birth to puberty.

The highest concentrations of epidermal growth factor (EGF) are found in urine, but the physiological role of urinary EGF is unknown. We studied human urinary EGF excretion, by measuring its concentration with a specific homologous RIA, in 265 healthy children from birth until age 16 yr. The absolute concentrations varied widely between individuals. Mean values were approximately 10 ng/ml in 1- to 30-day-old infants; 2.5-fold higher values were found in infants aged 2 to 12 months. During the second year there was a further rise to about 70 ng/ml, and urinary EGF excretion was in the same range in older subjects. The EGF/creatinine concentration ratio was less variable. The mean ratio increased 6-fold from birth to the second year of life. Thereafter, the EGF/creatinine ratio decreased gradually to one-third of the peak level at puberty. No sex difference was found.

Adolescent↗