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Intact and amino-terminally shortened forms of insulin-like growth factor I induce mammary gland differentiation and development.

Growth hormone (GH) plays a role in regulating growth and differentiation of immature glandular structures in the mammary gland, but the mechanisms by which the hormone exerts these effects are unknown. We have previously found that GH stimulates insulin-like growth factor I (IGF-I) I mRNA production within the mammary glands of hypophysectomized rats. In this study we set out to determine if IGF-I administration could mimic the action of GH in initiating mammary gland differentiation and development. Two forms of IGF-I, intact and amino-terminally shortened [des-(1-3)-IGF-I], were found to induce the development of terminal end buds and the formation of alveolar structures in the mammary glands of hypophysectomized, castrated, and estradiol-treated sexually immature male rats. The effect of both forms of IGF-I was similar to that obtained with human GH, but the truncated form was at least 5 times more potent than intact IGF-I. These findings suggest that the inductive effect of GH on glandular differentiation is mediated by the GH-induced production of IGF-I or a related molecule within the mammary gland itself.

Animals↗

Growth and development of Andean high altitude residents.

Growth and development under conditions of chronic hypoxia result in a different pattern of growth in Andean highlanders than in lowlanders. Growth at high altitude results in a small (1 to 4 cm) delay in linear growth, with most, if not all, of the delay probably established at or soon after birth. It also results in an enhancement of lung volumes, particularly residual volume, which is 70%-80% larger in highland than lowland children, on average, with the magnitude of the increase being positively related to age. In addition, growth and development under conditions of chronic hypoxia result in a blunted ventilatory response to hypoxia, a 4% to 5% reduction in Sa(O2), and a substantial increase in pulmonary diffusing capacity. Andean highlanders have V(O2 max) similar to that of lowlanders at low altitude, suggesting that they have successfully adapted to their hypoxic environment. It is likely that both developmental and genetic factors influence most, if not all, components of the cardiorespiratory system of Andean highlanders, but the relative importance of each is not clear.

Acclimatization↗

The role of fibroblast growth factor (FGF) and type beta transforming growth factor (TGF-beta 1-beta 2-beta 3) during rat craniofacial development.

Growth factors seem to be part of a complex cellular signalling language, in which individual growth factors are the equivalents of the letters that compose words. According to this analogy, informational content lies, not in an individual growth factor, but in the entire set of growth factors and others signals to which a cell is exposed. The ways in which growth factors exert their combinatorial effects are becoming clearer as the molecular mechanisms of growth factors actions are being investigated. A number of related extracellular signalling molecules that play widespread roles in regulating development in both invertebrates and vertebrates constitute the Fibroblast Growth Factor (FGF) and type beta Transforming Growth Factor (TGF beta). The latest research literature about the role and fate of these Growth factors and their influence in the craniofacial bone growth ad development is reviewed.

Animals↗

HIV-associated immune dysfunction and delayed pubertal development in a cohort of young hemophiliacs. Hemophilia Growth and Development Study.

As part of the Hemophilia Growth and Development Study (HGDS), we investigated the relationship between HIV-associated immune dysfunction and delayed pubertal development in a cohort of 333 boys and adolescents with moderate or severe hemophilia who were between the ages of 6 and 19 years at study entry in 1989. Sixty-two percent of the cohort was infected with HIV in the late 1970s and early 1980s through exposure to contaminated clotting factor concentrates. The cohort was observed during follow-up at 6-month intervals; measurements taken at each follow-up visit included Tanner stage and CD4+ cell count. This analysis of data from the first 4 years of follow-up revealed statistically significant delays in pubertal development associated with increasing levels of immune dysfunction. Our results emphasize the importance of following pubertal development in HIV-infected adolescent boys since delays in maturation may reflect underlying disease progression.

Adolescent↗

Fetal growth and development.

The foetal growth is, for the greater part, determined genetically. There are, however, favouring and inhibiting factors, which influence this growth. In such a matter, the mother, the placenta and the foetus play an important part. The mother shows as well metabolic as vascular adaptations. The placenta must let through nutrients and oxygen; the uteroplacental circulation is characterized by a high flow, together with a low vascular resistance. The foetus itself plays an important part owing to its own growth factors. The principal growth factors are insulin and the growth factors analogous to insulin. The slowing up of the intra-uterine growth is the consequence of genetic factors or of the decrease of the growth-potential. The real cause is, however, mostly a decrease of the vascular adaptation in the mother or a diminution of the uteroplacental circulation. The vascular causes usually induce an asymmetrical delay in the growth; foetal causes induce a symmetrical retardation. An exaggerated growth of the foetus--or macrosomy--is mostly due to an excessive inflow of nutrients: this is the case when a pregnant woman is suffering from diabetes. During the former years, it has become evident that abnormalities of the foetal growth influence the later life of people.

Animals↗

Enhanced sensitivity to tumor growth and development in multistage skin carcinogenesis by transforming growth factor-alpha-induced epidermal growth factor receptor activation but not p53 inactivation.

Transforming growth factor-alpha (TGF alpha) can stimulate keratinocyte proliferation and function as an autocrine tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated TGF alpha-transgenic mouse skin. In this study, we examined the effect of ectopic TGF alpha transgene expression on skin tumor growth and progression after DMBA initiation in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA). Both the multiplicity and size of skin tumors arising in TGF alpha-transgenic mice were significantly higher than those of the nontransgenic parental CD-1 strain. There were more dysplastic papillomas and squamous cell carcinomas (SCCs) in the transgenic animals as well. ProTGF alpha protein was expressed in transgenic papillomas, but mature TGF alpha was not detected. The epidermal growth factor receptor (EGFR) appeared to be downregulated and was associated with enhanced tyrosine phosphorylation of several substrates in TGF alpha-transgenic mouse tumors. Characteristic codon 61 mutations in the Ha-ras gene were found in most of the papillomas and SCCs induced by DMBA and TPA in transgenic as well as nontransgenic mice. However, no p53 gene mutations were found in any skin tumors from either transgenic or control animals. Analysis of cellular proliferation in both DMBA-TPA-induced papillomas and in skin 48 h after TPA treatment alone revealed significantly more DNA synthesis in TGF alpha-transgenic mice relative to controls. These results demonstrate that TGF alpha, through EGFR overstimulation, can act synergistically with TPA to induce the formation, growth, and development of DMBA-initiated skin tumors containing classic Ha-ras gene mutations but not p53 gene inactivation.

9,10-Dimethyl-1,2-benzanthracene↗

Comparability of absolute/percent CD4+ T-lymphocytes completed locally and centrally. Hemophilia Growth and Development Study.

The Hemophilia Growth and Development Study (HGDS) is a multicenter longitudinal study of 333 male children and adolescents with moderate or severe hemophilia, ranging in age from 6 to 19 at entry. Sixty-two percent of the cohort was infected with human immunodeficiency virus (HIV) in the late 1970s and early 1980s through exposure to contaminated clotting factor concentrates. The HGDS has followed this cohort since 1989. HGDS subjects have blood drawn twice each year for t-lymphocyte subsets, with fresh blood shipped overnight to a central laboratory. T-lymphocyte subsets from the same blood draw are often determined locally as well. To evaluate interlaboratory variation, we examined the comparability of pairs of local and central results for CD4+ absolute counts and percents. Ninety-four pairs of absolute counts and 73 pairs of percent CD4 + results were available. We calculated concordance correlation coefficients, which evaluate the agreement between two readings from the sample by measuring the variation from the 45 degrees line through the origin. Absolute counts were square root transformed. Comparability of the pairs was high for both absolute counts and percents (0.93 and 0.92, respectively). Agreement was high whether we determined the CD4+ counts and percents centrally, using fresh samples received the day after the examination (0.95, 0.95), or from specimens that were frozen upon receipt and batched for later testing (0.90, 0.87). We conclude that when a centrally processed CD4+ result is unavailable because of shipping problems or loss of specimens, a study may reasonably accept a CD4+ result completed locally, if validity checks indicate good comparability. In the HGDS, the data provided by the local laboratories were of comparable quality to those provided by the central laboratories.

Adolescent↗

Effects of iodine supplementation during pregnancy on child growth and development at school age.

Growth and development of 207 children (49% males; mean age 5.4 years [SD 0.2], range 4 to 7.3 years whose mothers received iodine during pregnancy, and children who received iodine first in their 2nd year, were examined in 1996; 192 children (49% males; mean age 6.5 years [SD 0.2], range 5.8 to 6.9 years) whose mothers received iodine while pregnant were seen in 1998. Children were from the southern part of China's Xinjiang Province which has the lowest levels of iodine in water and soil ever recorded. Head circumference but not height was improved for those who received iodine during pregnancy (compared with those receiving iodine at age 2) and for those supplemented before the end of the 2nd trimester (relative to those supplemented during the 3rd trimester). Iodine before the 3rd trimester predicted higher psychomotor test scores for children relative to those provided iodine later in pregnancy or at 2 years. Results from the test for cognitive development resulted in trend only differences between those children supplemented during pregnancy versus later. The results address the question of when maternal iodine supplements should begin in public health programs world wide. Findings may be relevant to the treatment of maternal and newborn thyroid deficiency in industrialized countries, particularly for those infants delivered before the end of the second trimester.

Administration, Oral↗

Abnormalities of lung growth and development.

Review of lung growth and development, as well as major congenital anomalies, is presented in this article. Emphasis is directed toward the difficulties these patients encounter later in life.

Humans↗