Expression of the insulin-like growth factor system in postpneumonectomy lung growth

The "cysteine string protein" (CSP) genes of higher eukaryotes code for a novel family of proteins characterized by a "J" domain and an unusual cysteine-rich region. Previous studies had localized the proteins in neuropil and synaptic terminals of larval and adult Drosophila and linked the temperature-sensitive paralysis of the mutants described here to conditional failure of synaptic transmission. We now use the null mutants as negative controls in order to reliably detect even low concentrations of CSPs by immunohistochemistry, employing three monoclonal antibodies. In wild-type flies high levels of cysteine string proteins are found not only in apparently all synaptic terminals of the embryonic, larval, and adult nervous systems, but also in the "tall cells" of the cardia, in the follicle cells of the ovary, in specific structures of the female spermatheca, and in the male testis and ejaculatory bulb. In addition, low levels of CSPs appear to be present in all tissues examined, including neuronal perikarya, axons, muscles, Malpighian tubules, and salivary glands. Western blots of isolated tissues demonstrate that of the four isoforms expressed in heads only the largest is found in non-neural organs. The wide expression of CSPs suggests that at least some of the various phenotypes of the null mutants observed at permissive temperatures, such as delayed development, short adult lifespan, modified electroretinogram, and optomotor behavior, may be caused by the lack of CSPs outside synaptic terminals.     

The role of growth hormone and insulin-like growth factors in the immune system

BACKGROUND AND PURPOSE: Understanding the nature and extent of fluctuations in spatial and temporal variables of gait (eg, speed, stride length [SL], stride time [ST]) over the course of the levodopa (L-dopa) cycle of individuals with advanced Parkinson disease (PD) is important in order to assess patients and examine the effectiveness of interventions. The purpose of this study was to determine whether gait variables are sufficiently stable to be used as outcome measures in a clinical trial involving patients with advanced PD. SUBJECTS: Five volunteers (3 male, 2 female; mean age=67.8 years; Hoehn and Yahr stages 3-4) with idiopathic PD of a mean duration of 15.0 years participated. METHODS: Gait speed, SL, and ST were measured as the subjects walked 7.2 m at self-selected speeds. To evaluate the full "on-off" sequence of the L-dopa response, this analysis was repeated 11 times, at intervals of 10% of the L-dopa cycle. Each subject was analyzed on 3 separate days, with approximately 1 month between tests. Two-way repeated-measures analyses of covariance, with 2 within-subject factors (percentage of L-dopa cycle and day) and 1 covariate (height), were applied, and coefficients of variation were calculated to determine the extent of change in speed, SL, and ST over the L-dopa cycle and over the 3 days. RESULTS: The subjects' overall mean gait speed was 70.39 cm/s, representing 55.4% of the age-related normative values. There were no effects of percentage of the L-dopa cycle or day or of the interaction of percentage of the L-dopa cycle and day on speed, SL, and ST. The coefficients of variation for speed and SL were consistently higher than the normative values, ranging from 13.5% to 23.8% and from 13.9% to 23.3% at 20% of the L-dopa cycle, respectively. CONCLUSION AND DISCUSSION: When interpreting spatiotemporal measurements of gait of patients with advanced PD, fluctuations can be extensive and may not follow a predictable pattern.     

Fetal growth velocity in the prediction of intrauterine growth retardation in a low risk population

Assignment of HLA-B types can be hampered by ambiguous reactivity of the typing sera resulting in inaccurate HLA-B assignments. In this study, 19 Korean samples exhibiting ambiguous serologic reactivities were characterized by DNA sequencing. Alleles identified from 7 samples were previously undetected in this population (B*1517, B*4101, B*4701, B*5001, and B*5106) and from 9 samples were common alleles in this population (B*4002, B*4003, B*4006, B*1501, B*1401, B*67012, and B*5401). Three samples were putative HLA-B homozygotes. Three major factors causing serologic ambiguity were identified: weak or false negative reactivity of typing sera (52.4%); cross or false positive reactivity of the sera (38.1%); and absence of information on the reaction patterns due to the lack of appropriate sera in the typing kit (e.g. B*4101 encoded molecule) or to the presence of recently characterized molecules (e.g. B*5106 encoded molecule) (9.5%). Overall, sequencing was helpful in clarifying ambiguous serologic reaction patterns improving the HLA typing for the Korean population.     

Comparative effect of growth hormone and plerocercoid growth factor in the intestinal resection in rat

OBJECTIVE: After massive bowel resection, absorption depends on how fast the mucosal adaptation takes place. This work aims at assessing the trophic effect of growth hormone (GH) and its analogue, the plerocercoid growth factor (PGF), on the intestinal mucosa after 90% small bowel resection. EXPERIMENTAL DESIGN: 24 male Wistar rats were divided into four groups of 6: Control (laparotomy), 90% small bowel resection (RID), resection and treatment with GH during 14 days (RID + GH) and resection and PGF treatment (RID + PGF). Intestinal mucosal adaptation was assessed by measuring mucosal weight and height, and evaluating the regenerative activity by measuring proliferation cell nuclear antigen (PCNA) labelling index. RESULTS: Bowel resection itself caused a significant increment of jejunal and ileal mucosal height in comparison with the control group. GH and PGF did not change this increase. Jejunal and ileal proliferation indexes were significantly higher than those in controls and they were significantly higher in both RID + GH and RID + PGF groups. CONCLUSIONS: GH and PGF cause a proliferative effect on the intestinal mucosa, even in hyperproliferative states such as the small bowel resection. This finding might have a clinic application.     

On the growth of electrometallurgy in Russia

A meeting of the Technical-Economic Council of the Department of Economics of the Metallurgical Industry was held at the end of March 2000. The meeting, chaired by department head A. Z. Shevtsov, examined two issues: modern electrometallurgy and the Russian-made 100-ton electric-arc furnace, which represents a new generation of furnaces; the creation of the noncommercial partnership “Union of Electrometallurgists.” Department of Economics of the Metallurgical Industry, Ministry of Economics of the Russian Federation. Translated from Metallurg, No. 6, p. 35, June, 2000.     

Interrelation of the therapeutic effects of growth hormone and testosterone on growth in hypopituitarism

The present study evaluates the modifying effect of growth hormone on the growth-promoting action of testosterone in boys at pubertal bone age. Growth and bone maturation were analyzed in 42 boys with primary or secondary Leydig cell insufficiency who had been treated with testosterone in an attempt to induce puberty and the accompanying growth spurt. The dosage given was considered normal or high for physiologic replacement therapy at puberty. Sixteen boys had normal GH secretion (seven had isolated gonadotropin deficiency, nine had congenital anorchia); 26 were GH and Gn deficient (20 idiopathic, six craniopharyngiomas). Of the GH-deficient patients, 12 received hGH simultaneously, while 14 received only testosterone. Results from each group were compared with the normal pubertal growth spurt in 15 untreated healthy boys. In isolated Gn deficiency and in congenital anorchia, the growth rates increased to above normal during the first six months of treatment, indicating that the testosterone dosage was probably too high for the beginning of puberty. During two subsequent six-month treatment periods, the rates leveled off close to normal. The same was true in the GH- and Gn-deficient patients on adequate hGH replacement. For contrast, there was minimal or no stimulation of growth when an even higher testosterone dose was given to GH- and Gn-deficient boys without hGH therapy. Bone maturation was normal in the boys with normal GH secretion or with hGH replacement, but was subnormal in the GH-deficient boys not treated with hGH. We conclude that testosterone exerts its full growth-promoting action only in the presence of normal endogenous GH secretion or with sufficient hGH replacement and that both hormones should be continued simultaneously until final adult height is achieved.     

Expression of growth hormone secretagogue-receptors by growth hormone-releasing hormone neurons in the mediobasal hypothalamus

A novel class of synthetic compounds, termed GH-secretagogues (GHSs), have been shown to be potent stimulators of GH release, although their mechanism of action and functional significance remains obscure. The recent cloning of the rat GHS receptor (GHS-R) permitted the identification of numerous sites of expression of GHS-R in brain, but nothing is yet known about the cell types that express this receptor. We performed dual chromogenic and autoradiographic in situ hybridization to test the hypothesis that GHRH neurons in the hypothalamus coexpress GHS-R mRNA. GHS-R-hybridizing cells showed extensive overlap with GHRH-expressing neurons in both the arcuate (Arc) and ventromedial (VMN) hypothalamic nuclei. Quantification of the double-labeled cells revealed that approximately 27% of GHRH-hybridizing neurons in the Arc, and 22% of those in the VMN, expressed the GHS-R gene. These studies are the first to colocalize the GHS-R to any neurochemical cell type in rat brain. The results provide evidence that the GHSs may directly modulate GHRH release, and thereby stimulate GH secretion, through interaction with the GHS-R on hypothalamic GHRH mRNA-containing neurons.     

Effect of growth rate dependent partition coefficient on the dendritic growth in undercooled melts

The theory of alloy dendritic growth at large undercoolings is extended to include the effect of growth rate dependent partition coefficient on the growth rate, tip radius and composition of dendrites. Three distinct behaviors are observed depending on the value of the dimensionless rate v. For small values of v, k ≅ k₀. For the intermediate range, when v is between 0.01 and 100, a significant effect of the velocity dependent partition coefficient is found. When v > 100, k → 1 and the dendrite behavior in an alloy is found to approach that for the pure material. In undercooled alloy melts segregation free zones could then be obtained by dendrite growth.     

Basic fibroblast growth factor enhances the growth of postnatal neostriatal GABAergic neurons in vitro

Basic fibroblast growth factor (bFGF) significantly enhances the short-term survival of embryonic striatal neurons in vitro but has little effect on the outgrowth of striatal cells compared to neurons from other brain regions. Studies in our laboratory have shown that bFGF protects postnatal striatal cells in vitro from NMDA receptor-induced neurotoxicity. We therefore examined the effects of bFGF on the outgrowth of GABA-containing cells taken from the postnatal (Day 1) caudate-putamen and cultured for up to 3 weeks. In control cultures GABAergic neurons formed three populations based on somatic size and developed the cytoarchitectural features characteristic of dendrites, spines, and axons. In the presence of bFGF (6 pM continuously from the day of plating), small- and medium-sized GABAergic neurons showed significant increases compared to untreated controls in axon-like growth (axon length) at 6 days in culture and in both axon- and dendrite-like neurite growth (axon length and branch order, number of primary dendrites, dendrite length, and dendritic branch order) at 13 and 17 days in culture. Large GABAergic neurons were unaffected by treatment with bFGF. Striatal GABAergic neurons exposed to nerve growth factor (10 ng/ml) were not different from untreated controls. Neuron survival was also unaffected by bFGF treatment at all days in culture examined. Other observations suggested that the neurotrophic effects of bFGF were mediated by a direct action of the growth factor on striatal neurons and not glial cells. First, glial cells (identified by the immunohistochemical localization of glial fibrillary acidic protein) were unaffected by bFGF treatment at the low concentration (6 pM) used to enhance neurite growth, but did significantly proliferate at higher concentrations of bFGF (6 nM). Second, immunoreactive bFGF receptor protein was localized predominantly to the somata and processes of striatal neurons and not to glial cells in the cultures. Finally, when neurons from control cultures were briefly exposed (1 to 4 h) to bFGF at concentrations which were neurotrophic, a marked elevation in the immediate early gene protein c-fos was observed by immunohistochemistry in the nuclei of neurons, including GABAergic cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Postnatal somatic growth and insulin contents in moderate or severe intrauterine growth retardation in the rat

Hematopoiesis in the vertebrate is characterized by the induction of ventral mesoderm to form hematopoietic stem cells and the eventual differentiation of these progenitors to form the peripheral blood lineages. Several genes have been implicated in the differentiation and development of hematopoietic and vascular progenitor cells, yet our understanding of the discrete steps involved in the induction of these cells from the ventral mesoderm is still incomplete. One method of delineating these processes is based on the use of lower vertebrates. The zebrafish (Danio rerio) is an especially robust vertebrate system for both isolating and characterizing genes involved in these processes. Hematopoietic mutants have been generated with defects in many of the steps of both the primitive and definitive hematopoietic programs. Cloning of the genes that underlie these mutations should yield valuable details of hematopoiesis and may have therapeutic implications for bone marrow transplantation and stem cell gene therapy.     

Basic fibroblast growth factor and insulinlike growth factor I support the growth of human septal chondrocytes in a serum-free environment

OBJECTIVE: To determine if insulinlike growth factor I (IGF-I) and basic fibroblast growth factor (bFGF), individually or in combination, support the growth and viability of human septal chondrocytes in a serum-free medium (SFM) and a serum-enhanced culture medium. DESIGN: Chondrocytes were recovered from enzymatically digested human septal cartilage and were plated for monolayer culture in a newly developed medium. The medium included Dulbecco modified Eagle medium mixed 1:1 with Ham F12 medium and a supplement of known amounts of 2 growth factors-bFGF (100 ng/mL) and IGF-I (100 ng/mL)-used in combination and separately. RESULTS: The combination of IGF-I and bFGF enhanced chondrocyte growth and maintained a high degree of viability in SFM and 10% fetal calf serum. After an initial lag, the SFM, augmented with both growth factors, produced a comparable number of viable cells (4.25+/-0.31 x 10(4)) to that of the medium with 10% fetal calf serum (4.64+/-0.35 x 10(4)) by the seventh day of the experiment. Combined with the 2 growth factors, 10% fetal calf serum provided the greatest proliferation by the end of the experiment. However, the overall mean cell counts for the IGF-I- and bFGF-enhanced SFM were not statistically different. CONCLUSIONS: The combination of IGF-I and bFGF in a serum-free and a serum-supplemented environment supports the growth and viability of human septal chondrocytes in short-term culture. In an SFM, the results obtained approximate those produced in a medium enhanced with 10% fetal calf serum.     

Plasma growth hormone concentrations during growth in turkeys

Cytology in malignant melanoma of the skin is a useful method, which alone yields in many cases enough diagnostic informations for a therapeutical approach. It is of a special importance in cases with marked anisocytosis of cells and with large, sometimes polynuclear cells and with cells with melanotic pigment. In cases with middle-sized apigmented cells of epitheloid appearance it should be always completed by biopsy, which, in these cases predominates over cytology. Combination of both methods brings a more substantial elucidation of diagnosis.     

Differential effect of insulin-like growth factor-1 and growth hormone on hypothalamic regulation of growth hormone secretion in the rat

Pharmacological administration of either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) were reported to inhibit endogenous GH release in humans and in the laboratory animal. We have evaluated the short-term differential mechanisms whereby the two hormones affect hypothalamic regulation of GH secretion. Wistar male rats (90 days old) were injected i.p. with either GH (recombinant GH NIAMDD, Baltimore, MD, USA), rIGF-1 (Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan) or saline. Animals were sacrificed at 15, 30, 60 and 120 minutes following injection. Hypothalami were dissected and extracted immediately and the levels of growth hormone-releasing hormone (GHRH) and somatostatin were determined using specific antisera. Trunk blood was collected for GH and IGF-1 determination by RIA. Administration of IGF-1 or GH markedly decreased hypothalamic somatostatin stores by 77% and 54% respectively, within 15 minutes. Concomitantly, the wide range of GH levels found in the control group was reduced in the IGF-1 treated group suggesting that the pulsatile pattern of GH secretion was suppressed. Growth hormone administration induced an increase in hypothalamic GHRH stores (60% at 120 minutes). During this period serum IGF-1 levels were not altered. It is suggested that short term modulation of hypothalamic neurohormones by GH and IGF-1 is mediated by rapid stimulation of somatostatin release by both hormones, and inhibition of GHRH release is induced only by GH.     

Modeling the relationship between growth in rapid naming speed and growth in decoding skill in first-grade children.

This study used an extant longitudinal correlational data set (D. L. Compton, 2000) to model the relationship between growth in decoding skill and growth in rapid automatized naming (RAN) in 1st-grade children. During an academic year, 75 1st-grade children were assessed 7 times (once per month) in word reading, nonword reading, RAN numbers, and RAN colors. Results indicated a unique relationship between RAN numbers and early decoding skill. A bidirectional relationship between decoding skill and RAN numbers was supported, with RAN performance prior to the acquisition of decoding skill predictive of future decoding skill and with increased growth in RAN facilitated by the acquisition of decoding skill. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The growth of pain and the pain of growth.

Reviews the book, Textbook of pain by Patrick D. Wall and Ronald Melzack (1984). A clinical specialty has come of age when it is represented by a textbook of this stature. Wall and Melzack's 79-chapter Textbook of Pain attempts, as Noordenbos describes in his prologue, to represent the state of the art today, to be a guideline on how to tackle the subject, and finally, to prescribe how to act in a given situation. As a textbook, it also must accomplish these goals through chapters that are accessible to readers at less advanced levels or working in different disciplines. In this instance, the difficulty of the textbook creators' task is compounded by the nature of the specialty of studying and treating pain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Widespread growth retardation and variable growth recovery in foster children in the first year after initial placement

OBJECTIVES: To determine children's growth patterns in the first year of foster care placement and to compare catch-up growth with initial height percentile as indicators of prior growth retardation. DESIGN: Inception cohort. SUBJECTS: Forty-five children aged 1 1/2 to 6.0 years in their first year of foster care. SETTING: Urban, community-based primary care center. MAIN OUTCOME MEASURES: Height, weight, weight-for-height, and annual growth velocity z scores 1 year after placement. RESULTS: The group entered foster care with an overall height deficit (height z = -0.21), grew at an above-average rate (velocity z = +0.33), and eliminated the height deficit by the end of the year (height z = -0.02; P < .05). Weight increased (baseline weight z = -0.16; year-end weight z = +0.35) and correlated with height z change (r = 0.385, P = .009). Weight for expected weight-for-height-age was above average and did not change (baseline weight for expected weight-for-height-age z = +0.30; year-end weight for expected weight-for-height-age z = +0.40). Baseline age correlated with velocity z (r = .413, P = .005) but not with change in height z. Baseline height z did not correlate with either velocity z or change in height z. Three patterns of growth were seen: 21 (47%) showed catch-up growth (height velocity z = 1.34; gain in height z = +0.61); 16 (36%) showed stable growth; and 8 (18%) showed poor growth (height velocity z = -1.49; decrease in height z = -0.49). CONCLUSIONS: Almost half of the children showed significant catch-up growth in the first year after foster care placement, indicating probable prior growth failure. Initial height was not predictive of future growth, and simple screening (such as height less than the fifth percentile) would have missed the majority of children who showed catch-up growth. A substantial minority (18%) continued to decline across height percentiles after placement. The initial and subsequent growth failure and catch-up growth in this population did not appear to be related to nutritional changes.