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Biomedical subjects

J Perheentupa

Publications and source records attributed to J Perheentupa.

At least 91 records · Page 5Linked to original sources

Copper supplementation: failure to increase plasma copper and ceruloplasmin concentrations in healthy infants.

Plasma copper and ceruloplasmin concentrations at ages 0, 2, 4, 6, 9, and 12 mo were longitudinally evaluated in our Finnish nutritional survey of 200 infants. The infants, who were weaned by age 3.5 mo, were randomly assigned to receive either a liquid cow-milk-based formula containing 1.3 mumol Cu/L (n = 16) or the same formula supplemented with 7.8 mumol Cu/L as Cu sulfate (n = 16). They were compared with exclusively breast-fed infants. Plasma Cu and ceruloplasmin concentrations increased steadily and similarly in all three groups from 4.6 +/- 0.2 mumol/L (means +/- SEM) and 0.9 +/- 0.1 mumol/L, respectively, in umbilical samples to 19.7 +/- 0.3 mumol/L and 3.2 +/- 0.1 mumol/L, respectively, at age 12 mo. Our results indicate that concentrations of plasma Cu and ceruloplasmin in healthy full-term infants are resistant to dietary supplementation.

Age Factors↗

Aetiology of congenital hypothyroidism in Finland.

In Finland a nationwide screening programme for congenital hypothyroidism (CHT) has operated since 1980 with complete coverage. Among the total of 307,000 newborns screened, the incidence per 100,000 was 24.6 for thyroid dysgenesis and 4.0 for dyshormonogenesis. We conclude that, when screening is based on cord serum TSH, the false-positive results are caused mainly by difficult delivery. The most important factors associated with dyshormonogenesis were CHT in the family, origin from a geographic risk area, and origin of both mother and father from the same community. These reflect the autosomal recessive inheritance. The risk factors for dysgenesis were female gender, CHT in the family, birth in a geographic risk area, and birth during a risk period of the year.

Congenital Hypothyroidism↗

Multivariate analysis of psychomotor development in congenital hypothyroidism.

In the Finnish programme of screening for congenital hypothyroidism (CHT), thyroid replacement therapy is started very early (at a median age of 6 days). Our experience with the first 50 patients detected by this programme confirms that clinically relevant mental retardation is avoided by early therapy. But some intrauterine damage is inevitable and its degree correlates with the severity of the CHT. Age at the start of therapy, in our narrow range, did not appear to influence the outcome, as we found only a paradoxical positive correlation between the two. Our results suggest that thyroid hormone is transferred from the mother to her hypothyroid child during delivery.

Child Development↗

Bone age at birth; method and effect of hypothyroidism.

Bone maturity at birth (or during the neonatal period) can be estimated from the ossified distal femoral epiphyses (FE). In congenital hypothyroidism (CHT) bone maturation is retarded and neonatal bone age reflects the severity of prenatal thyroid failure. In our reference group of 111 healthy infants, the size of these epiphyses depended not only on the age but also on body size. Thus, if bone age is estimated from the size of an epiphysis, the size of the infant is a potential confounder. This problem was avoided by estimating the maturation lag from the difference between the observed and predicted heights of FE (FEHs). Models for predicting FEH were constructed from data from the reference group by multiple linear regression and confirmed in a separate group of 37 healthy infants. In 52 hypothyroid newborns both FEH and FEH lag correlated with serum thyroxine concentration, indicating that FEH can be used as a measure of bone maturation in a population that is fairly homogeneous for (postmenstrual) age and size. Otherwise FEH lag is a better indicator.

Age Determination by Skeleton↗

Growth evaluation: parent and child specific height standards.

Data on the growth of 1063 children and their parents were analysed. Of the variation in height at prepuberty about 20%, and of the final height 30-46%, were explained by the variation in parental heights; the children's own height at the age of 1.0 year increased the proportion explained to half. Two equations were developed for increasing the accuracy of the evaluation of growth. One defines parent specific mean height standard deviation score, and the other includes the parents' heights and the child's height at the age of 1.0 year and defines expected standard deviation score for height. These equations are easy to use if they are converted to nomograms.

Aging↗

Effects of estradiol and progesterone on epidermal growth factor concentration in plasma, bile, urine, submandibular gland and kidney of the mouse.

Testosterone is known to increase epidermal growth factor (EGF) concentrations in mouse plasma and submandibular salivary gland. We tested in adult sialoadenectomized (sx) and sham-operated female and male mice our hypothesis that female sex steroids also affect EGF concentrations in fluids and tissues. In 10-day treatment estradiol-17 beta increased the EGF concentration in male urine and in (sx) female plasma. Progesterone increased the concentration in both sexes in plasma (sx mice) and in the kidneys. In contrast, progesterone decreased it in female urine.

Animals↗

EGF- and TGF-alpha-like peptides in human fetal gut.

The presence of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) immunoreactivities in fetal human tissues was studied immunohistochemically at different gestational ages. EGF and TGF alpha immunoreactivities were detected from the 20th gestational wk. EGF immunoreactivity was limited to the small intestine, but TGF alpha immunoreactive cells were present in the colon also. According to radioreceptor assay, the intestine of a 19-wk-old human fetus contained 10 times more EGF receptor-binding substance than EGF, as measured by immunofluorometric assay. Chromatographic analysis suggests that TGF alpha-like peptides account for at least part of this activity, as so argues in favor of the presence of TGF alpha- and EGF-like peptides in the human fetal gut. Whether they are synthesized in the fetus is yet unknown.

Digestive System↗

Characterization of material with epidermal growth factor immunoreactivity in human serum and platelets.

We investigated the molecular nature of the epidermal growth factor immunoreactivity (ir-EGF) in serum and platelets of normal subjects. In serum, ir-EGF appeared and increased during spontaneous blood coagulation, reaching a plateau in 2 h. The mean plateau measured by time-resolved immunofluorometric assay was 778 pg/mL [130 pmol/L; range, 465-1352 pg/mL (78-225 pmol/L)] for men (n = 66), and 774 pg/mL (129 pmoL/L; range, 521-1114 pg/mL (87-186 pmol/L)] for women (n = 33). Serum samples (n = 9), when examined under nonreducing conditions by high performance liquid chromatography, contained three mol wt components. Their approximate proportions averaged 56 +/- 6% (+/- SD) for a 140K component, 22 +/- 9% for a 67K component, and 22 +/- 6% for a component coeluting with the 6K EGF standard. The molecular size distribution of ir-EGF released from isolated platelets varied with the treatment of the platelets. After stimulation with a Ca2+ ionophore, the proportions of the 140K, 67K, and 6K components were 61 +/- 11%, 20 +/- 8%, and 17 +/- 4% (n = 5), respectively, as in serum. In addition, we found a small amount, (approximately 1%) of a 17K component. When platelets (n = 6) were ruptured by sonication and repeated freeze-thawing, the 67K component formed 53 +/- 7% of the total; the proportions of the 140K, 17K, and 6K components were 14 +/- 7%, 2.1 +/- 0.7%, and 31 +/- 4%, respectively. Under reducing conditions the 17K and 6K components remained intact, but part of the 140K component and all of the 67K component were cleaved to a 35-37K form. After protease digestion of the higher mol wt components, the ir-EGF was exclusively of the 6K form. The 67K and 6K components bound to the EGF receptor, whereas the 140K component bound inconsistently. We conclude that treatment of platelets with Ca2+ ionophore produces ir-EGF components similar to those found in incubated serum but different from those obtained by freeze-thawing. The 67K mol wt component appears to be the main storage form of EGF in platelets; at least two independent mechanisms appear to exist for EGF release.

Blood Coagulation↗

Epidermal growth factor stimulates prostacyclin production by cultured human vascular endothelial cells.

Epidermal growth factor (EGF) stimulated prostacyclin (PGI2) production by cultured human umbilical vein endothelial cells, as measured by radioimmunoassay of its stable metabolite 6-keto-prostaglandin F1 alpha. This effect of EGF was dose-dependent, the lowest stimulatory concentration of EGF was 1.0 ng/ml and 100 ng/ml caused a 2.7 +/- 0.3 (mean +/- SEM) fold increase in the PGI2 synthesis. The stimulation appeared at 3-6 h of incubation and lasted at least 24 h. It was suppressed by EGF antibodies and blocked by protein synthesis inhibitor cycloheximide. Cells preincubated 12 h with EGF released also higher amounts of PGI2 when incubated with thrombin for 5 min. It is concluded that EGF liberated from platelets during aggregation may prevent local thrombogenesis and atherogenesis by stimulating the release of the antiaggregatory, vasodilatory PGI2 from vascular endothelial cells.

6-Ketoprostaglandin F1 alpha↗

Craniopharyngioma surgery in children: endocrine and visual outcome.

Twenty-two children with craniopharyngioma were operated on in our Department of Neurosurgery from 1970 to 1981. Removal was total in 11 patients. There was one surgical death, but no recurrences in this group. Only partial removal could be performed in 10 children, followed by stereotactic radiotherapy in one. Recurrences have occurred in 4 of these children and 2 of them have died. In 1 child a biopsy was performed, followed by insertion of a shunt and stereotactic radiotherapy. Nine years after treatment there have still been no recurrences. Visual acuity was unchanged after the procedure in 17/21 survivors, improved in 1, and deteriorated in 3. The visual fields remained unchanged in 11, improved in 3, and deteriorated in 7. The visual fields and visual acuity were normal postoperatively in 5 patients. Hypopituitarism was more extensive after the procedure. We recommended an attempt at total removal whenever possible.

Child↗

Testosterone substitution increases the activity of lipoprotein lipase and hepatic lipase in hypogonadal males.

We studied the effects of testosterone substitution on serum concentrations of lipids, lipoproteins, apoproteins and on the activity of hepatic lipase (HL) and lipoprotein lipase (LPL) in postheparin plasma and on the activity of LPL in adipose tissue (AT-LPL) in 13 male hypopituitary patients. The activities of LPL and HL in postheparin plasma were markedly increased by 1 week after a testosterone enanthate injection (P less than 0.001). The HL activity remained elevated (P less than 0.05) after 1 month's treatment, but the LPL activity declined to presubstitution levels. The prolonged substitution decreased serum apoproteins A-I and A-II (P less than 0.05). The changes of apo A-I and A-II correlated inversely with those of the free testosterone index (FTI) (r = -0.74, r = -0.67, P less than 0.05). Serum HDL-cholesterol level decreased slightly by 1 week and it correlated inversely with the increase in testosterone and the FTI (r = -0.67, r = -0.85, P less than 0.05). The results suggest that testosterone increases the activity of both lipolytic enzymes in postheparin plasma. The effect on HL appears to be more persistent than that on LPL. The data support a role for androgens in the regulation of serum lipoprotein and HDL-cholesterol levels.

Adipose Tissue↗

The parotid gland is the main source of human salivary epidermal growth factor.

To clarify the production of human epidermal growth factor (EGF) by different salivary glands, we measured its concentration by radioimmunoassay separately in whole saliva, in parotid gland (PG) saliva and in mixed submandibular (SMG) and sublingual gland (SLG) saliva. Also, we studied the presence of EGF in PG and SMG by immunohistochemistry. The mean (geometric) concentrations of EGF in PG saliva (2704 pg/ml, +/- SEM interval 2393-3056 pg/ml, n = 20) was higher (p less than 0.001) than in whole saliva (864 pg/ml, +/- 733-1019 pg/ml, n = 29), which in turn was higher (p less than 0.001) than in mixed SMG + SLG saliva (357 pg/ml, +/- 296-430 pg/ml, n = 16). No sex difference existed in any salivary gland EGF. Immunohistochemistry revealed EGF in the acinar cells of both PG and SMG, but only in PG there were prominent EGF deposits in luminal spaces. Our data suggest that EGF is produced by both PG and SMG, but that more of it is secreted from the PG. This result is new and challenges the general view that human salivary EGF is mainly from SMG. In mouse almost all salivary EGF comes from SMG and its amount is androgen dependent. Thus there are great differences in sources and regulation of salivary EGF between man and mouse.

Adult↗

Elevated adipose tissue lipoprotein lipase activity in craniopharyngioma patients.

The activity of lipoprotein lipase (LPL) was measured in adipose tissue (AT-LPL) and postheparin plasma (PH-LPL) of 13 obese patients (aged 11 to 31 years) who had surgery for craniopharyngioma 1 to 13 years earlier. AT-LPL activity (mean +/- SEM) was higher in them than in subjects matched with respect to age, sex, and relative body weight (4.6 +/- 1.1 v 2.1 +/- 0.4 mumol free fatty acids (FFA).h-1.g-1, P less than .05). The activity was also higher when expressed per fat cell.

Adipose Tissue↗

Postoperative computed tomographic control of 38 patients with craniopharyngioma.

Computed tomography scanning was performed on 38 patients 1-12 years after surgery for craniopharyngioma. Recurrence of the tumor had appeared in nine patients. Thirteen patients had a residual tumor, and 16 were tumor-free after primary surgery. In addition, one patient became tumor-free after total removal of the recurrent tumor. After partial removal, the rate of recurrence was high and the quality of life was impaired.

Adolescent↗

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↗

Turner syndrome: effect of hormone therapies on height velocity and adult height.

76 patients with Turner syndrome received estrogen alone, androgen and estrogen started simultaneously or, after preceding androgen therapy, estrogen with or without androgen. Six patients had spontaneous pubertal development and received no estrogen. Two patients received human growth hormone with androgen during greater than 2.0 years. Height velocity increased during all therapies to mean SD scores of 7.6 during androgen-estrogen started simultaneously, 4.6 during androgen alone, 4.2 during androgen-estrogen after preceding androgen, 2.7 during estrogen alone, and 0.6 during estrogen after preceding androgen. Adult height was measured in all cases, it was 145.5 +/- 5.7 (mean +/- SD) for the whole series without significant differences between the groups. It correlated strongly with midparent height, and was greater for patients with the 45,X karyotype than for the others combined.

Adolescent↗

Plasma antibodies to cow's milk are increased by early weaning and consumption of unmodified milk, but production of plasma IgA and IgM cow's milk antibodies is stimulated even during exclusive breast-feeding.

We measured levels of cow's milk-specific (CM) antibodies of immunoglobulin classes G, A and M by enzyme-linked immunosorbent assay in plasma of 198 healthy infants; a variable number of samples taken at birth and at ages of 2, 4, 6, 9, 12 and 28 months were available (altogether 765 samples). The rise in the level of IgG CM antibodies was highest and most rapid in infants exposed to CM formula before the age of 1 month. The level fell by 9 months, but rose again by 12 months. This second rise was attributed to the introduction of dairy milk. Partially breast-fed and fully weaned infants had similar levels of IgG CM antibodies. The levels of IgG CM antibodies were unaffected by the infants' own atopy, their heredity for atopy, and the umbilical serum level of IgG CM antibodies. IgA and IgM CM antibodies were absent at birth. Their levels increased similarly in exclusively breast-fed infants and infants fed CM formula. We conclude that plasma IgG antibodies to cow's milk are increased by early weaning and by consumption of unmodified cow's milk. Production of plasma IgA and IgM antibodies to cow's milk is stimulated even during exclusive breast-feeding.

Age Factors↗