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J Perheentupa

Publications and source records attributed to J Perheentupa.

At least 73 records · Page 4Linked to original sources

Human milk stimulates prostacyclin production by cultured human vascular endothelial cells.

Prostacyclin (PGI2) is an antithrombotic and vasodilatory factor, which is produced mainly by the vascular endothelium. Little is known about how this process is regulated. We investigated the effect of human milk on PGI2 synthesis by human vascular endothelial cells by measuring its stable metabolite, 6-keto-prostaglandin F1 alpha, by RIA. Human milk induced dose- and time-dependent stimulation of PGI2 production, whereas cow's milk was ineffective. The lowest concentration of human milk that stimulated the production of PGI2 was 0.1%, and 10% induced a 2.4- to 3.4-fold increase. The effect of human milk was detectable after 2 h and was blocked by inhibitors of transcription, translation, and cyclooxygenase. Boiling abolished the activity, but acetone extraction enhanced it. A 10% concentration of acetone-extracted human milk stimulated the release of endothelial cell PGI2 by 6.6-fold. In human milk samples we found no correlation between the amount of immunoreactive epidermal growth factor (EGF) and the activity stimulating PGI2 synthesis. Furthermore, EGF antibodies did not inhibit the activity. This is the first demonstration that human milk stimulates PGI2 production by endothelial cells. We conclude that human milk is a potent inducer of PGI2 production by human vascular endothelial cells and that the stimulatory activity is not due to EGF.

6-Ketoprostaglandin F1 alpha↗

Ocular disease leads to decreased concentrations of epidermal growth factor in the tear fluid.

The concentration of epidermal growth factor (EGF) in tear fluid (TF) was recently shown to decrease with increasing tear fluid flow (TFF). The purpose of the present study was to clarify the effects of ocular surface disease on the TF EGF concentrations. Tear fluid samples (n = 243) were collected from diseased eyes by means of blunted glass capillaries. The time of collection was measured for each sample, and the tear fluid flow in the capillaries (TFFc) was calculated. The concentration of human EGF (hEGF) was determined using a time-resolved immunofluorometric assay (TR-IFMA). For statistical analysis diagnosis-dependent multigrouping was performed and the data of the patient groups were compared to the data for a control group. The control material consisted of 271 TF samples collected from healthy eyes before (n = 59) and after stimulation of reflex tearing (n = 212). It was shown that TF specimens of patients (n = 243) contained significantly (p less than 0.001) less EGF (mean 952 pg/ml) than the TF of healthy control individuals before (n = 59 samples; mean 6589 pg/ml) or after stimulation of reflex tearing (n = 212 samples; mean 2762 pg/ml). The EGF concentration of every patient group was significantly lower than that found in the TF of control individuals both before and during reflex tearing (p less than 0.001). The rate of EGF released with TF during collection did not differ significantly between the various groups of patients or from that released with the TF of normal individuals before induction of reflex tearing.(ABSTRACT TRUNCATED AT 250 WORDS)

Corneal Diseases↗

Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients.

To define the clinical picture and course of the autosomal recessive disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), we report data from our 10-month to 31-year follow-up of 68 patients from 54 families, now 10 months to 53 years of age. The clinical manifestations varied greatly and included from one to eight disease components, 63 percent of the patients having three to five of them. The initial manifestation was oral candidiasis in 41 patients (60 percent), intestinal malabsorption in 6 (9 percent), and keratopathy in 2 (3 percent). All the patients had candidiasis at some time. The earliest endocrine component appeared at 19 months to 35 years of age. Hypoparathyroidism was present in 54 patients (79 percent), adrenocortical failure in 49 (72 percent), and gonadal failure in 15 (60 percent) of the female patients greater than or equal to 13 years of age and 4 (14 percent) of the male patients greater than or equal to 16 years of age. There were multiple endocrine deficiencies in half the patients. From 4 to 29 percent of the patients had periodic malabsorption, gastric parietal-cell atrophy, hepatitis, alopecia, vitiligo, or a combination of these conditions. Dental-enamel hypoplasia and keratopathy were also frequent but were not attributable to hypoparathyroidism. In the patients whose initial manifestation (other than candidiasis) was adrenal failure, the other components developed less often than in the remaining patients. We conclude that the clinical spectrum in patients with APECED is broad. The majority of patients have three to five manifestations, some of which may not appear until the fifth decade. Therefore, all patients need lifelong follow-up for the detection of new components of the disease.

Adolescent↗

Estrogen-androgen antagonism in the regulation of epidermal growth factor in mouse submandibular salivary gland and kidneys.

To eludicate hormonal regulation of epidermal growth factor (EGF) concentration we studied the effects in adult female mice of ovariectomy and postovariectomy treatments with testosterone plus estradiol on the EGF concentrations in submandibular salivary gland (SMG), plasma, kidneys and urine. In the tissues, we also studied the location of EGF immunohistochemically and measured EGF mRNA. After ovariectomy, SMG EGF first decreased to one third of preovariectomy level. After postovariectomy day 10 it started to increase and reached by day 80 3.5-fold the preovariectomy level. Simultaneously, EGF mRNA increased. Testosterone treatment further strongly augmented the levels of both EGF mRNA and EGF. A small dose of estradiol counteracted slightly the mRNA effect of testosterone. After ovariectomy plasma EGF first increased 1.3-fold by day 10, then returned to the initial levels, and rose again 1.6-fold by day 80. Testosterone treatment induced a further 1.5-fold increase. Estradiol did not counteract this effect. Kidney EGF decreased 15% by postovariectomy day 20. This was preceded by a decrease in EGF mRNA from day 10 onwards. The EGF concentration recovered during the 80 days, but the EGF mRNA level stayed low. Testosterone treatment further reduced the levels of both EGF mRNA and EGF. This effect was counteracted by estradiol. Urine EGF increased after ovariectomy to a peak (1.7-fold) by day 40. It then returned to the preovariectomy levels by day 80. Testosterone treatment increased urinary EGF 1.9-fold; concomitant estradiol had no effect.

Androgen Antagonists↗

Variation of growth in length and weight of children. I. Years 1 and 2.

As part of our work aiming at facilitation of growth screening, we analyzed the growth of 741 healthy infants from birth to 2 years of age. We 1) show that weight depends on length rather than age, 2) present new growth standards in a format which allows direct reading of relative length and relative weight, and 3) define the normal variation of changes over different periods in terms of relative length (SD score, SDS) and relative weight (deviation of weight from the median weight for length and sex, %DW). The group mean values for changes in length SDS and %DW were zero, but there were wide individual variations, which decreased with age and length. We present curves defining these variations for use in growth screening.

Age Factors↗

Variation of growth in height and weight of children. II. After infancy.

To provide for early detection of abnormal changes in growth, we propose the monitoring of all children for changes in relative height and relative weight as indirect indicators of growth velocity. To this end we analyzed the growth of 2,156 children, as recorded by the child health surveillance services at ages 2 to 19 years. From their data we constructed growth standards on charts of a novel type, which allow direct reading of relative height (SD score, SDS) and relative weight (percentage deviation of weight from median weight for height and sex, %DW). Variation in height explained most (mean 60%) of the variation in weight, and age did not contribute significantly. Hence, our weight charts are height-based. Next, we defined the variations of changes in (delta) SDS and %DW during the different periods of growth. The group means of changes in each period were zero. Variation in delta SDS is widest at the earliest ages, then decreases until year 9-10 (girls) and 10-11 (boys), and again increases. For delta %DW the picture is similar. We present these variations as diagrams for use in growth screening.

Adolescent↗

Effects of epidermal growth factor on bone formation and resorption in vivo.

The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double [3H]proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in the periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g-1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at physiological doses induces distinct effects on endosteal and periosteal bone formation and that the effects are dependent on EGF dosage and duration of treatment. This study indicates that EGF at physiological dosage stimulates periosteal bone formation and increases endosteal bone resorption in the growing mouse.

Alkaline Phosphatase↗

Plasmin and epidermal growth factor in the tear fluid of contact-lens wearers: effect of wearing different types of contact lenses and association with clinical findings.

The concentrations of plasmin and epidermal growth factor were determined in tear fluid (TF) samples from wearers of different types of contact lenses (CLs) during and after cessation of CL wear (CLW). TF samples of 50 healthy eyes served as controls. The plasmin concentrations in the control group (0.4 +/- 0.1 microgram/ml; mean +/- SEM) were significantly lower (p less than 0.001) than in the group of soft CL (SCL) wearers during CLW (1.2 +/- 0.2 microgram/ml). Cessation of CLW led to a decrease in TF plasmin concentrations from 1.2 +/- 0.2 to 0.6 +/- 0.1 micrograms/ml in the group of SCL wearers (p less than 0.001), from 1.5 +/- 1.1 to 0.3 +/- 0.2 micrograms/ml in the group of extended-wear SCL wearers (p greater than 0.05) and from 0.4 +/- 0.3 to 0.0 +/- 0.0 microgram/ml in the group of gas-permeable CL wearers (p greater than 0.05). After CLW cessation, TF plasmin levels of CL wearers did not differ from those of controls. The occurrence of plasmin in TF was associated with a higher degree of corneal neovascularization and with the presence of limbal injection. The concentrations of epidermal growth factor in TF were not significantly altered by the discontinuation of CLW.

Conjunctiva↗

Pulsatile secretion of LH and FSH in prepubertal and early pubertal boys revealed by ultrasensitive time-resolved immunofluorometric assays.

Pulsatile secretion of LH and FSH was examined in 10 prepubertal (aged 4.5-12.9 y) and seven early pubertal (aged 12.8-14.5 y) boys with ultrasensitive (0.019 and 0.014 IU/L) time-resolved immunofluorometric assays. Plasma LH and FSH levels were measured every 15 or 20 min for 6 h during the day and night. The lowest mean LH level in a prepubertal boy was 0.02 IU/L and in eight other prepubertal boys mean LH levels were less than 0.4 IU/L. In early pubertal boys the mean LH levels ranged from 0.3 to 6.5 IU/L. The difference in mean FSH level between prepubertal (0.61 IU/L) and early pubertal boys (1.85 IU/L) was smaller than the difference in LH level. All boys had significant LH and FSH pulses. The LH interpulse interval was 135 +/- 86 min (mean +/- SD) and 76 +/- 65 min for the prepubertal and pubertal boys, respectively (p less than 0.01). For FSH, the respective values were 150 +/- 122 and 221 +/- 157 min (p = NS). The mean LH pulse amplitudes were 11-fold greater in the early pubertal boys than in the prepubertal boys, whereas the mean FSH pulse amplitudes were similar between the two groups. The present method shows that the mean LH levels in prepubertal boys are much lower, and the increase during puberty larger, than previously reported. The increase is apparently due to increased pulse frequency and amplitude. The increase in mean FSH level is smaller and evidently not caused by an increase in pulse frequency or pulse amplitude.

Adolescent↗

Gonadal control of pulsatile secretion of luteinizing hormone and follicle-stimulating hormone in prepubertal boys evaluated by ultrasensitive time-resolved immunofluorometric assays.

To elucidate the role of the testis in the control of LH and FSH secretion before puberty, we examined pulsatile LH and FSH secretion in six prepubertal boys with primary testicular failure (two boys with masculine pseudohermaphroditism, two boys with the Klinefelter's syndrome, and two boys with anorchia) and eight normal prepubertal boys. Plasma LH and FSH levels were measured every 15 min for 6 h during the day and night with ultrasensitive (0.019 and 0.014 IU/L) time-resolved immunofluorometric assays. In all six hypogonadal boys the mean FSH level was above the range of the normal prepubertal boys, whereas the LH level was elevated in only one boy. All boys had LH and FSH pulses. The FSH pulse interval in the anorchid boys was shorter than that in the normal boys, but this was not observed in the other hypogonadal boys. The LH pulse interval in the anorchid and other hypogonadal boys was the same as that in the normal boys. The FSH pulse amplitudes were higher in the anorchid and other hypogonadal boys than in the normal boys, but the LH pulse amplitudes were higher only in the anorchid boys. We conclude that in prepuberty the testes have little effect on LH secretion, but that they are involved in the regulation of FSH levels. In primary testicular failure, the elevation of FSH levels is associated with an increase in FSH pulse amplitude and, in the absence of testicular steroids, possibly also with an increase in FSH pulse frequency.

Age Factors↗

Epidermal growth factor in mice: effects of estradiol, testosterone and dexamethasone.

To clarify the influence of steroids on the metabolism of epidermal growth factor, we studied the effects on its concentrations in adult male and female mice of 1. gonadectomy, 2. postgonadectomy treatments with estradiol and testosterone, and 3. treatment with dexamethasone. We also measured its mRNA levels in submandibular salivary glands and kidneys after ovariectomy. After gonadectomy, the male mice had 1.4-fold higher mean epidermal growth factor concentration in the urine than the female, in contrast to a 1.5-fold reverse difference in intact mice; the female mice had 2.5-fold higher concentration in the submandibular glands than the male animals, in contrast to a 4.5-fold reverse difference in intact mice. The kidney sex difference of intact mice (male greater than female) was abolished. In both gonadectomized sexes, treatment with testosterone increased the concentration of epidermal growth factor in plasma and the submandibular gland; treatment with estradiol increased the concentration in urine and decreased it in the submandibular gland. Treatment with dexamethasone decreased the concentration of epidermal growth factor in plasma of the male mice, and in urine of the female mice, thus decreasing the sex differences. In the submandibular gland and the kidneys, dexamethasone increased the concentration. The mRNA levels were higher in the submandibular gland and lower in the kidneys in the ovariectomized than in the intact female mice. The effects of sex steroids on epidermal growth factor concentrations are mediated through modulation of its gene activity. Testosterone has an increasing and estradiol a decreasing effect in the submandibular gland. Estradiol has also an increasing effect in the kidneys.

Animals↗

Epidermal growth factor in mice: changes during circadian and female reproductive cycles.

To clarify the variation of mouse epidermal growth factor production during the 24-h and female reproductive cycles, we measured its concentrations in the plasma, submandibular salivary gland, urine, kidneys and liver of adult male and female mice during consecutive 12-h dark and 12-h light periods, different stages of pregnancy, and lactation. The concentration of epidermal growth factor in the submandibular gland showed no circadian changes. In plasma and in the liver it increased during the dark period, whereas in urine and in the kidneys it peaked in the daytime. In the submandibular gland the concentration decreased during early pregnancy, but it returned to the non-pregnant levels by mid-pregnancy. In plasma it decreased progressively during pregnancy and recovered during lactation. In urine and the kidneys the concentration of epidermal growth factor increased after early pregnancy; with a further great increase in the kidneys during lactation. In the liver the concentration was clearly below the non-pregnant levels during late pregnancy and lactation.

Animals↗

Hormonal background of the hypertension and fluid derangements associated with adrenocorticotrophic hormone treatment of infants.

We studied the hormonal background of the fluid derangements and arterial hypertension associated with adrenocorticotrophic hormone (ACTH) treatment for infantile spasms in ten infants aged 5-22 months. They received a 6 week course of (carboxymethyl-cellulose-)ACTH: 80 IU at 0800 hours daily in weeks 1-3, then tapering, and termination at the end of week 6. The infants showed large, variable increases in 24 h urine cortisol during treatment. The mean plasma cortisol concentration (24 h after ACTH injection) was not significantly increased, but was correlated with the relative dose of ACTH. The mean plasma aldosterone concentration decreased. No significant change occurred in plasma renin activity (PRA), or in the concentrations of renin substrate (RS) or arginine vasopressin (AVP). Seven infants developed arterial hypertension, which was severe in three. This severe hypertension was associated with the highest relative ACTH doses and the highest plasma RS and cortisol concentrations. In the group as a whole, systolic blood pressure correlated with plasma RS and cortisol concentrations, but not with the other parameters. At the end of treatment urine and plasma cortisol dropped below the pretreatment levels and stayed low for greater than 2 weeks. There was a sharp peak in PRA and plasma aldosterone concentration, and a decrease in plasma RS. Plasma AVP levels dropped markedly. The mean body weight increased sharply and urine flow decreased. Mean plasma electrolyte levels remained unaltered. The danger at termination of ACTH treatment appears to be associated with a sudden transition from hypercortisolism to hypocortisolism, activation of the renin-angiotensin-aldosterone axis, and suppression of AVP secretion.

Adrenocorticotropic Hormone↗

Epidermal growth factor is a constant component of normal human tear fluid.

Epidermal growth factor (EGF) is a mitogenic polypeptide, which was first isolated from mouse submaxillary gland. Since EGF also stimulates the growth of corneal epithelial cells and only preliminary data exist on its presence in tear fluid, we studied the occurrence of human EGF (hEGF) in the tear fluid of 36 healthy persons (31 women and 5 men from 20 to 59 years of age; 60 eyes). hEGF, as measured by an immunofluorometric assay, was present in all tear fluid samples investigated. Its concentration varied from 200 to 2860 pg/ml (median, 705 pg/ml). The tear fluid hEGF concentrations differed less between the eyes of one individual than between individuals. The total amount of hEGF released to the tear fluid increased with fluid flow, but the higher the flow was, the lower the concentration of hEGF. We could not find any evidence of sex dependency in the hEGF concentrations. In demonstrating that hEGF is a normal component of human tear fluid, the results of this study suggest that hEGF may be important for conjunctival and corneal epithelial integrity.

Adult↗

Mouse epidermal growth factor concentrations are altered by gonadectomy and treatments with estradiol and progesterone.

In adult male and female mice we compared the epidermal growth factor (EGF) concentrations after gonadectomy and studied the effects of postgonadectomy treatments with estradiol and progesterone. In gonadectomized mice the mean concentration of EGF in the submandibular salivary gland (SMG) was (7-fold) higher in the females than the males. In the kidneys the males had (1.3-fold) higher levels of EGF than the females. Yet, gonadectomized males had higher plasma EGF levels and females higher urinary EGF concentrations. Estradiol treatment clearly decreased the EGF concentration in the SMG and increased it in urine and kidneys. Progesterone decreased male kidney EGF. Combined treatment with estradiol and progesterone increased the EGF concentration in the male urine and SMG, and decreased it in male kidneys.

Animals↗

Cholesterol and its precursors in human milk during prolonged exclusive breast-feeding.

Concentrations of cholesterol and its precursors were investigated in human milk from 88 mothers at 2 mo, 28 mothers at 6 mo, and 6 mothers at 9 mo of lactation. These mothers, who were exclusively breast-feeding their infants, collected fore- and hindmilk samples at every feeding over a 24-h period. Samples were analyzed by gas-liquid chromatography and mass spectrometry. Mean (+/- SD) cholesterol concentrations were 0.41 +/- 0.094, 0.46 +/- 0.094, and 0.49 +/- 0.10 mmol/L, respectively. The following cholesterol precursors were identified: squalene, lanosterol, dimethylsterol, delta 8.24-methostenol, lathosterol, and desmosterol. Mean concentrations were 0.04 +/- 0.11, 0.35 +/- 0.13, and 0.29 +/- 0.012 mmol/L for desmosterol, 0.0094 +/- 0.0027, 0.012 +/- 0.0039, and 0.011 +/- 0.0039 mmol/L for squalene, and from 0.0011 to 0.0027 mmol/L for all the other precursors. The precursors' equally low concentrations, except for desmosterol and squalene, and the significant correlations with each other suggest that the mammary gland synthesizes cholesterol from lanosterol by preserving the side-chain double bond and that the rate-limiting step may be the conversion of desmosterol to cholesterol.

Adult↗