bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Anti‐hGH Antibodies during Therapy with Authentic Human Growth Hormone
Authors: LUNDIN K. , BERGER L. , BLOMBERG F. , WILTON P.
Published: April 2008

ABSTRACT. Children treated with authentic human growth hormone (Genotropin) in clinical trials between 1985 and 1989 were tested for the presence of anti‐hGH antibodies. The incidence of antibodies after 12 months of treatment was 4/373 (1.1%). Mean binding capacity was 0.07 mg/1. The results suggest that Genotropin has low immunogenicity.
Insulin‐like growth factor binding proteins: a proposed superfamily
Authors: Hwa V , Oh Y , Rosenfeld RG
Published: April 2008

Hwa V, Oh Y, Rosenfeld RG. Insulin‐like growth factor binding proteins: a proposed superfamily. Acta Pzdiatr 1999; Suppl 428:37‐45. Stockholm. ISSN 0803‐5326

The conventional concept is that the insulin‐like growth factor binding proteins (IGFBPs) are cysteine‐rich proteins, with conserved N‐ and C‐domains, that are capable of binding insulin‐like growth factors (IGFs) with high affinity. This dogma was recently challenged by the discovery of a group of cysteine‐rich proteins that share important structural similarities with the IGFBPs, but have demonstrably lower affinity for IGFs. It is therefore proposed that these IGFBP‐related proteins (IGFBP‐rPs) and the IGFBPs constitute an IGFBP superfamily. We speculate that the IGFBP superfamily is derived from an ancestral gene/protein that was critically involved in the regulation of cell growth and was capable of binding IGF peptides. Over the course of evolution, some members (IGFBPs) evolved into high‐affinity IGF binders and others (IGFBP‐rPs) into low‐affinity IGF binders, thereby conferring on the IGFBP superfamily the ability to influence cell growth by both IGF‐dependent and IGF‐independent means. 0 Insulin‐like growth factor binding protein, insulin‐like growth factor binding protein‐related protein, superfamily
Insulin resistance in short children with intrauterine growth retardation
Authors: Chiarelli F , Ricco L di , Mohn A , Martino M De , Verrotti A
Published: April 2008

Chiarelli F, di Ricco L, Mohn A, De Martino M, Verrotti A. Insulin resistance in short children with intrauterine growth retardation. Acta Pædiatr 1999; Suppl 428: 62–5. Stockholm. ISSN 0803–5326

Scientific evidence is accumulating for an association between intrauterine growth retardation (IUGR) and an increased risk of developing adult degenerative diseases, such as essential hypertension, non‐insulin‐dependent diabetes mellitus and ischaemic heart disease. A possible underlying mechanism for these conditions is insulin resistance. In this paper, mechanisms and methods of measurement of insulin resistance are briefly reviewed, and recent studies on the evaluation of insulin resistance in short children with IUGR are summarized. In our experience, short prepubertal children with IUGR show consistent insulin resistance, which becomes particularly evident during pubertal development. □Intrauterine growth retardation, insulin resistance, short children
Evidence for an association between birth weight and blood pressure
Authors: Hindmarsh PC , Brook CGD
Published: April 2008

Hindmarsh PC, Brook CGD. Evidence for an association between birth weight and blood pressure. Acta Pædiatr 1999; Suppl 428: 66–9. Stockholm. ISSN 0803–5326

Evidence is presented to support the concept that there is an association between birth weight and blood pressure in humans. This relationship probably reflects an interaction between the genetic make‐up of the individual and the environment. On average, a decrease in birth weight is associated with a rise in blood pressure in adult life. □Birth weight, blood pressure, fetal growth, hypertension
Final height of growth hormone‐treated patients with growth hormone deficiency: the North American experience
Authors: Hintz RL
Published: April 2008

Hintz RL. Final height of growth hormone‐treated patients with growth hormone deficiency: the North American experience. Acta Pædiatr 1999; Suppl 428: 70–1. Stockholm. ISSN 0803–5326

The results of treatment of growth hormone (GH)‐deficient patients with recombinant GH are better than the results of treatment with pituitary GH. The reasons for this improvement include higher dosages, more consistent treatment, and daily administration. Under ideal circumstances, final height in patients with GH deficiency (GHD) can be within the normal range for adult height with GH treatment, and brought close to their target height. To achieve this result, it is important to diagnose and treat GHD early, use adequate doses of GH, and continue treatment until final height. □Growth hormone, growth hormone deficiency, final height
High‐dose growth hormone (GH) treatment in prepubertal GH‐deficient children
Authors: Yokoya S , Araki K , Igarashi Y , Kohno H , Nishi Y , Hasegawa Y , Fujita K , Iwatani N , Tachibana K , Ohyama Y , Seino Y , Satoh M , Fujieda K , Tanaka T
Published: April 2008

Yokoya S, Araki K, Igarashi Y, Kohno H, Nishi Y, Hasegawa Y, Fujita K, Iwatani N, Tachibana K, Ohyama Y, Seino Y, Satoh M, Fujieda K, Tanaka T. High‐dose growth hormone (GH) treatment in prepubertal GH‐deficient children. Acta Pædiatr 1999; Suppl 428: 76–9. Stockholm. ISSN 0803–5326

Two clinical studies were conducted to determine the effect of different doses of growth hormone (GH) on prepubertal growth in GH‐deficient boys. In one study, GH doses of 1.0 and 1.5 IU/kg/week (0.33 and 0.5 mg/kg/week) were given to groups of five children and compared with a conventional Japanese dose of 0.5 IU/kg/week (0.17 mg/kg/week) in 15 children. A significant dose‐dependent increase in height velocity occurred in the first year of treatment, but differences between doses were not significant thereafter. In a second study, GH was administered to ten boys at a dose of 0.5 IU/kg/week for the first year, 0.75 IU/kg/week for the second year, 1.0 IU/kg/week for the third year and 0.5 IU/kg/week for the fourth and subsequent years (0.17, 0.25, 0.33 and 0.17 mg/kg/week, respectively). During the second and third years of GH treatment, these boys had significantly higher growth rates than controls, who were given GH at 0.5 IU/kg/week (0.17 mg/kg/week) throughout, indicating successful reduction in‘waning’of the treatment effect. At the end of the fourth year, the different protocols from the two studies had both resulted in a greater height SDS than the controls, and did not advance bone maturation. In conclusion, these protocols may be effective in increasing prepubertal height gain in children with GH deficiency. □Growth hormone, growth hormone deficiency, high dose
Can growth hormone counteract the effects of glucocorticoids on protein metabolism?
Authors: Beaufrère B
Published: April 2008

Beaufrère B. Can growth hormone counteract the effects of glucocorticoids on protein metabolism? Acta Pædiatr 1999; Suppl 428: 97–9. Stockholm. ISSN 0803–5326

The size of the body's protein pool depends on the equilibrium between protein synthesis and breakdown. Glucocorticoids, the most potent catabolic hormones, act primarily by increasing protein breakdown, both in muscle and at the whole‐body level. Growth hormone (GH) counteracts the catabolic effects of glucocorticoids by stimulating protein synthesis. Part of its effects are mediated via insulin‐like growth factor I (IGF‐I). The effects of combined GH‐IGF‐I treatment are discussed. □Glucocorticoids, growth hormone, insulin, insulin‐like growth factor I, protein breakdown, protein synthesis
Methodological considerations in the assessment of health‐related quality of life in children
Authors: Erling A
Published: April 2008

Erling A. Methodological considerations in the assessment of health‐related quality of life in children. Acta Pædiatr 1999; Suppl 428: 106–7. Stockholm. ISSN 0803–5326

Health‐related quality of life (HRQL) can be described as the psychological and social aspects of a patient's health, and as the patient's view of his or her condition and its treatment. Doctors, parents and children have different views of a child's HRQL. This is not because one has the right perception and the others are wrong, but because they see different aspects of the child's HRQL. Only the children themselves can provide a subjective perception of their HRQL. The practical and conceptual considerations required when assessing children's HRQL are discussed. □Children, health‐related quality of life
Peer relationships and quality of life
Authors: Bukowski WM , Sandberg D
Published: April 2008

Bukowski WM, Sandberg D. Peer relationships and quality of life. Acta Pædiatr 1999; Suppl 428: 108–9. Stockholm. ISSN 0803–5326

Measures of peer relationships during childhood have been shown to be reliable predictors of several indicators of functioning during adulthood. Within each of these areas of functioning, children who have troubled peer relationships are more likely to show signs of distress than are other children. In addition, experiences with peers appear to provide a context for the development of many fundamental human capacities (e.g., moral judgement, conflict resolution skills, emotional regulation, etc.). Three interrelated levels of analysis can be used to assess a child's experiences with peers: the level of the individual (i.e., what the child is like); the level of the dyad (e.g., experiences with friends); and the level of the group (e.g., experiences with the set of individuals with whom the child typically associates). By determining a child's functioning at these three levels of analysis (using assessments from teachers, parents, and peers), it is possible to obtain a good assessment of a central portion of the quality of a child's life. Such measures have been used to assess the quality of life of children across the height spectrum and preliminary findings show that the peer experiences of children who are substantially shorter than their peers are remarkably similar to those of other children. □Behavioural development, Paediatric development, peer experience, quality of life
Relationship between phenotype and genotype in growth hormone insensitivity syndrome
Authors: Woods KA , Clark AJL , Amselem S , Savage MO
Published: April 2008

Woods KA, Clark AJL, Amselem S, Savage MO. Relationship between phenotype and genotype in growth hormone insensitivity syndrome. Acta Pædiatr 1999; Suppl 428: 158–62. Stockholm. ISSN 0803–5326

Growth hormone insensitivity syndrome (GHIS) of genetic origin is associated with many different mutations of the growth hormone receptor (GHR) gene and a recently described genetic defect of the insulin‐like growth factor I (IGF‐I) gene. Phenotypic and biochemical features were examined in a cohort of 82 patients with GHIS from 23 countries. The mean age of these patients was 8.3 years, their mean height SDS was ‐6.09 and their median IGF‐binding protein‐3 (IGFBP‐3) SDS was ‐8.5. In total, 19 of the 82 patients (23%) were growth hormone‐binding protein (GHBP)‐positive (> 10%). The mean heights in GHBP‐negative and GHBP‐positive patients were ‐6.45 SDS and ‐4.89 SDS, respectively (p < 0.001). Sixteen different GHR gene mutations were identified in 27 patients with GHIS. All of these patients had homozygous mutations, except one who had a compound heterozygous mutation. There was no relationship between the type or site within the GHR gene of the mutation and the height SDS or IGFBP‐3 SDS of the patients. GHIS is associated with a wide variation in the severity of clinical and biochemical phenotypes. This variation cannot clearly be accounted for by defects in the GHR gene alone. Other genes or environmental factors must contribute to the control of growth in patients with GHIS. □Growth hormone, growth hormone insensitivity, growth hormone receptor gene
Truncated growth hormone receptor isoforms
Authors: Ross RJM
Published: April 2008

Ross RJM. Truncated growth hormone receptor isoforms. Acta Pædiatr 1999; Suppl 428: 164–6. Stockholm. ISSN 0803–5326

Truncated forms of the growth hormone receptor (GHR) that lack the majority of the cytoplasmic domain have been identified in a number of human tissues. In vitro, these truncated receptors act as dominant‐negative inhibitors of the growth hormone (GH) signal and also generate large amounts of growth hormone binding protein (GHBP). Mutations that lead to high levels of expression of the truncated GHR are associated with short stature and GH insensitivity. Thus, truncated GHRs may be important as a physiological regulator of GH signalling in addition to providing a mechanism for the production of GHBR □Cirrhosis, growth hormone, growth hormone insensitivity, growth hormone receptor, growth hormone resistance, truncated growth hormone receptor
Serum levels of insulin‐like growth factor binding proteins in Ecuadorean children with growth hormone insensitivity
Authors: Burren CP , Wanek D , Mohan S , Cohen P , Guevara‐Aguirre J , Rosenfeld RG
Published: April 2008

Burren CP, Wanek D, Mohan S, Cohen P, Guevara‐Aguirre J, Rosenfeld RG. Serum levels of insulin‐like growth factor binding proteins in Ecuadorean children with growth hormone insensitivity. Acta Pædiatr 1999; Suppl 428: 185–91. Stockholm. ISSN 0803–5326

Although insulin‐like growth factor binding proteins (IGFBPs) are known to be important modulators of the action of insulin‐like growth factors (IGFs), regulation of their production in vivo is not completely understood. Serum concentrations of IGFBP‐3, ‐4 and ‐5 and acid‐labile subunit (ALS) were therefore examined in 20 children with growth hormone (GH) insensitivity before and after 6 months of therapy with recombinant human IGF‐I (80 or 120 ug/kg twice daily). The IGFBP concentrations in these children were compared with those in 62 GH‐deficient children receiving GH therapy for 3 months. Serum levels of IGFBP‐3, ‐4 and ‐5 and ALS all increased significantly (p < 0.0001) in GH‐deficient children in response to GH therapy, whereas no significant increases occurred in the children with GH insensitivity. These findings indicate that GH is responsible for the regulation of serum levels of IGFBP‐3, ‐4 and ‐5 and ALS, and that IGF‐I does not directly regulate the concentrations of these circulating IGFBPs. □Growth hormone, growth hormone insensitivity, insulin‐like growth factor I, insulin‐like growth factor binding protein
Partial growth hormone insensitivity ‐ idiopathic short stature is not always idiopathic
Authors: Saenger P
Published: April 2008

Saenger P. Partial growth hormone insensitivity ‐ idiopathic short stature is not always idiopathic. Acta Pædiatr 1999; Suppl 428: 194–8. Stockholm. ISSN 0803–5326

Heterozygous growth hormone receptor (GHR) gene defects are not a common cause of idiopathic short stature. Although some of these GHR mutations may result in relative insensitivity to growth hormone (GH) in other studies, obligate heterozygotes did not present any clinical manifestations. Although patients with GH insensitivity and elevated GH binding protein (GHBP) levels have been described, it may be a reasonable approach to screen children who have growth failure, low levels of insulin‐like growth factor‐I (IGF‐I) and IGF‐binding protein‐3, and low levels of GHBP. Whether the sensitivity of this screening approach can be increased by administering pharmacological doses of GH for a few days and measuring the resultant increase in serum IGF‐I concentration remains to be determined by ongoing studies. □Growth hormone insensitivity, growth hormone receptor, short stature
Overview of the effects of cancer therapies: the nature, scale and breadth of the problem
Authors: Sklar C A
Published: April 2008

Over the past 30 years, the striking improvements in the survival rates of patients with childhood cancers are due, in large part, to the use of aggressive treatment strtegies. These therapeutic modalities are associated with a variety of late complications that span a spectrum from minor and treatable to serious and occasionally lethal. Nearly one‐quarter of the late deaths in survivors of childhood cancer can be attributed to a treatment‐related effect, for example, a subsequent malignant neoplasm or cardiac dysfuntion. The risk of late death due to causes other than recurrence is greatest in survivors treated with the combination of chemotherapy and radiotherapy. Among the 650 survivors followed in the Long‐Term Follow‐Up Clinic at the Memorial Sloan‐Kettering Cancer Center, the most common sequelae are endocrine complications, which are seen in 40% of the patients. Growth hormone deficiency, primary hypothyroidism and primary ovarian failure are the endocrine disorders observed most often.
Restoration of spermatogenesis by hormone treatment after cytotoxic therapy
Authors: Meistrich ML
Published: April 2008

Cytotoxic therapy is effective in treating various cancers, but many of the agents used can cause sterility in men, regardless of the age at which they were treated. Originally, it was thought that infertility in individuals who had undergone cytotoxic therapy resulted from the destruction of stem spermatogonia. However, studies using rats suggest that some stem spermatogonia can survive cytotoxic therapy and that infertility is caused by the inability of these spermatogonia to differentiate. The author believes that the failure of these cells to differentiate may be related to the high levels of intratesticular testosterone encountered in these situations. In rats that have previously received cytotoxic therapy, the administration of a gonadotrophin‐releasing hormone (GnRH) agonist restores the ability of spermatogonia to differentiate, and as a result normal spermatogenesis returns. This finding suggests that GnRH agonists show promise as treatment for male sterility induced by cytotoxic therapy, although further studies are required.
The transmission of prions to humans
Authors: Will RG
Published: April 2008

The identification of new‐variant Creutzfeldt‐Jakob disease (nvCJD) in 1996 led to the proposalhd that this new disease was caused by the transmission of bovine spongiform encephalopathy (BSE)ve epidemiologyof Creutzfeldt‐jakob disease in six to the human population. The ramifications of such a proposal have been extensive and profound,8; 43: 763–7 both politically and on the general public in the UK and other countries. Patients with nvCJD: 960–70 exhibit a consistent set of clinicopathological features, and cases of nvCJD continue to be reportedob disease (spongiform enceer almost exclusively in the UK, the country with by far the highest incidence of BSE. Laboratory studies, including transmission experiments in mice, provide strong support for the hypothesis that nvCJD is caused by BSE.
HESX1: a novel gene implicated in a familial form of septo‐optic dysplasia
Authors: Dattani MT , Martinez‐Barbera JP , Thomas PQ , Brickman JM , Gupta R , Wales JKH , Hindmarsh PC , Beddington RSP , Robinson ICAF
Published: April 2008

The homeobox gene Hesxl, which encodes a pituitary transcription factor, is first expressed at gastrulation in the mouse embryo. Hesxl expression begins in prospective forebrain tissue but later becomes restricted to Rathke's pouch, the primordium of the anterior pituitary gland. Transgenic mice lacking Hesxl exhibit a phenotype comprising variable anterior CNS defects, such as a reduced prosencephalon, abnormalities in the cropus callosum and septum pellucidum, anophthalmia or microphthalmia, defective olfactory development and bifurcations in Rathke's pouch with pituitary dysplasia. A comparable and highly variable phenotype in humans is septo‐optic dysplasia. We have cloned and sequenced the human homologue HESXl and screened for mutations in affected individual using single‐stranded conformational polymorphism analysis. Two siblings with septo‐optic dysplasia were homozygous for a missense mutation within the HESXl This mutation resulted in the substitution of a highly conserved arginine residue (Arg53) by cysteine and led to a loss of in vitro DNA binding. Hence, a vital role for Hesxl/HESXl in forebrain and pituitary development in mice and humans is suggested.
The molecular basis of premature adrenarche: an hypothesis
Authors: Miller Walter L
Published: April 2008

Adrenarche is characterized by a prepubertal rise in adrenal secretion of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) that is independent of the gonads or gonadotropins. Adrenopause is the corresponding diminution in DHEA and DHEAS concentrations in later life. The mechanisms by which adrenarche and adrenopause are induced and regulated are unknown. Early work focused on identifying hypothetical adrenal androgen regulatory hormones that would induce DHEA in much the same way that adrenocorticotropin induces cortisol, but no such factors have been found. Current studies of adrenarche focus on intra‐adrenal events, particularly those concerning 3β‐hydroxysteroid dehydrogenase (3β‐HSD) and 17α‐hydroxylase/17,20‐lyase (P450c17). Molecular data implicate a decrease in 3β‐HSD specifically in the adrenal zona reticularis. However, a decrease in 3β‐HSD is insufficient to explain why the reticularis catalyzes 17,20‐lyase activity and hence makes DHEA, rather than catalyzing only 17α‐hydroxylase activity, as does the zona fasciculata. P450c17 appears to catalyze 17,20‐lyase activity only if P450c17 has undergone serine phosphorylation and has access to cytochrome b5 as an allosteric cofactor. Although these two factors have not yet been investigated in adrenarche, it appears that both a zone‐specific diminution in 3β‐HSD and a zone‐specific induction of 17,20‐lyase activity are required to account for the physiological data. Exaggerated premature adrenarche appears to be an early sign of polycystic ovary syndrome (PCOS). Mechanistic considerations of PCOS suggest a key role for serine phosphorylation of P450c17 in both adrenarche and some forms of heritable PCOS.
Regulation of mineral metabolism from fetus to infant: metabolic studies
Authors: O'Brien KO
Published: April 2008

Optimal mineral intake is crucial, especially during the period of rapid growth that occurs during infancy and childhood. Two minerals that have been found to play key roles during this period are iron and zinc. Supplementation studies have shown that these minerals have significant effects on birth weight as well as on weight and height increase during childhood. However, because a myriad of nutritional factors influence growth, it has often been difficult to characterize the role of any given mineral on fetal and early childhood growth. Stable iron and zinc isotopes can be used to study how the mineral status of iron‐ and zinc‐deficient pregnant women affects their ability to absorb and transfer iron to the fetus. Furthermore, these isotopic tracers can be employed to examine the ability of infants to modify mineral absorption over time as the mineral stores of birth are depleted. Further studies using stable mineral isotopes during gestation, infancy and childhood will provide additional information on the regulation of mineral absorption and transport during these key periods of growth.
The role of leptin in human growth and puberty
Authors: Ong KKL , Ahmed ML , Dunger DB
Published: April 2008

Experimental animal studies demonstrate the effects of leptin on appetite, weight gain and metabolism. The biological effects of leptin in human adults are still to be determined, but recent reports show that congenital leptin deficiency leads to hyperphagia and excessive weight gain from early infancy as well as failure of pubertal onset in adolescence. Our recently reported data from two longitudinal cohorts suggest a role for leptin in the normal regulation of childhood weight gain, maturation and the development of secondary sexual features and body composition. Low leptin levels in cord blood closely reflected decreased adiposity at birth and stringly predicted high rates of weight gain in infancy and cath‐up growth. In adolescents, leptin levels rose gradually with age prior to puberty, suggesting that a threshold effect may trigger puberty. In girls, low leptin levels at the start of puberty predicted large gains in the percentage of fat mass, perhaps suggesting a role in the preparation for childbearing.
Body composition in Prader‐Willi syndrome: assessment and effects of growth hormone administration
Authors: Davies PSW
Published: April 2008

Children and adults with Prader‐Willi syndrome are usually overweight, if not obese. Nevertheless, it is now thought that the body composition exhibited by such individuals is markedly dissimilar to that found in simple obesity. In fact, the body composition typical of Prader‐Willi syndrome is actually more characteristic of that found in individuals with growth hormone (GH) deficiency, namely an increased level of adiposity in the limbs in comparison with the trunk and an overall reduction in fat‐free mass. This variation in body composition may impact upon the assumptions inherent in many techniques used to measure body size and body composition, such as the use of body mass index and skinfolds. Therefore, it is important that the potential error in body composition assessment is understood by professionals evaluating patients with Prader‐Willi syndrome. Accurate assessment of body composition is critical in Prader‐Willi syndrome, as a number of recent studies have revealed extremely similar findings relating to the effect of exogenous GH on the body composition of patients with this syndrome. Other notable findings of these studies include significant increases in muscle strength and exercise capacity, which probably result from the changes in body composition. The routine use of exsogenous GH to treat this extremely debilitating syndrome should now be considered.
Turner syndrome: a pattern of early growth failure
Authors: Davenport ML , Punyasavatsut N , Gunther D , Savendahl L , Stewart PW
Published: April 2008

The purpose of this study was to determine the pattern of early growth in girls with Turner syndrome. Analysis was performed on a total of 464 longitudinal measurements of height, obtained from birth to 8 years of age from 37 girls with Turner syndrome who did not have significant cardiac disease or autosomal abnormalities. All data were obtained prior to the initiation of any hormonal therapy. Mean height SDS fell from ‐0.5 at birth to ‐1.5 at age 1 year and ‐1.8 at age 1.5 years. Growth curves fitted using the first two components of the infancy‐childhood‐puberty model of growth revealed that growth failure was due to (a) mild growth retardation in utero, (b) slow growth during infancy, (c) delayed onset of the childhood component of growth and (d) slow growth during childhood. Physicians should consider the diagnosis of Turner syndrome in any girl with an unexplained failure to thrive or with short stature, even during the first 2 years of life.
Growth hormone treatment regimens in girls with Turner syndrome
Authors: Muinck SMPF de , Schrama Keizer , Sas TCJ ,   the Dutch Advisory Group on Growth Hormone
Published: April 2008

To optimize growth hormone (GH) treatment in girls with Turner syndrome, two multicentre studies were carried out in The Netherlands: a frequency‐response study (study 2) and a dose‐response study (study 2). In study 1, 19 girls with Turner syndrome, aged 11 years or older, were treated with one or two daily injections of GH at a total dose of IU/m2/day (0.067 mg/kg/day) and ethinyloestradiol given orally at a dose of 0.05 μg/kg/day. All the girls reached final height. The mean (±SD) gain in final height was not significantly different between the once‐ or twice‐daily regimens (7.6 ± 2.3 versus 5.1 ± 3.2 cm, respectively). The mean final height attained was 155.5 ± 5.4 cm. All the girls exceeded their adult height prediction. In study 2, 68 girls with Turner syndrome, aged 2‐11 years, were randomized into three dosage groups: A, B and C. During the first year, the girls in all the groups received GH at a dose of 4 IU/m2/day (0.045 mg/kg/day), which group A continued to receive throughout the study. At the start of the second year groups B and C were switched to a dose of 6 IU/m2/day, which the girls in group B continued to receive for the reminder of the study. At the start of the third year, the girls in group C were switched to a dose of 8 IU/m2/day (0.090 mg/kg/day) for the remainder of the study. After 7 years of GH treatment, height SDS (based on Turner syndrome and normal population references) increased significantly in all three groups, but significantly more in groups B and C compared with group A (p= 0.02 and p=0.001, respectively). Predicted adult height increased significantly, without a significant difference between the three groups. The mean final heights of 25 of the girls were 159.1, 161.8 and 162.7 cm for groups A, B and C, respectively.
Recurrent abdominal pain due to buckshots in the appendix
Authors: Zampieri Nicola , Zuin Veronica , Ottolenghi Alberto , Camoglio Francesco Saverio
Published: April 2008

Ingestion of foreign bodies is a common paediatric problem, with more than 100 000 cases occurring each year. The majority of these objects are radiopaque. This paper reports a case of elective appendectomy in a patient with unknown ingestion of buckshots affected by recurrent abdominal pain. Plain abdominal films and ultrasound scans showed that the foreign bodies were located in the right lower abdominal quadrant, more specifically in the appendix.

Conclusion: Foreign bodies in the appendiceal lumen may cause inflammation, perforation and peritonitis. Surgery seems to be the only effective therapeutic approach to foreign bodies in the appendix.
Role of disulfide bonds in goose‐type lysozyme
Authors: Kawamura Shunsuke , Ohkuma Mari , Chijiiwa Yuki , Kohno Daiki , Nakagawa Hiroyuki , Hirakawa Hideki , Kuhara Satoru , Torikata Takao
Published: April 2008

The role of the two disulfide bonds (Cys4–Cys60 and Cys18–Cys29) in the activity and stability of goose‐type (G‐type) lysozyme was investigated using ostrich egg‐white lysozyme as a model. Each of the two disulfide bonds was deleted separately or simultaneously by substituting both Cys residues with either Ser or Ala. No remarkable differences in secondary structure or catalytic activity were observed between the wild‐type and mutant proteins. However, thermal and guanidine hydrochloride unfolding experiments revealed that the stabilities of mutants lacking one or both of the disulfide bonds were significantly decreased relative to those of the wild‐type. The destabilization energies of mutant proteins agreed well with those predicted from entropic effects in the denatured state. The effects of deleting each disulfide bond on protein stability were found to be approximately additive, indicating that the individual disulfide bonds contribute to the stability of G‐type lysozyme in an independent manner. Under reducing conditions, the thermal stability of the wild‐type was decreased to a level nearly equivalent to that of a Cys‐free mutant (C4S/C18S/C29S/C60S) in which all Cys residues were replaced by Ser. Moreover, the optimum temperature of the catalytic activity for the Cys‐free mutant was downshifted by about 20 °C as compared with that of the wild‐type. These results indicate that the formation of the two disulfide bonds is not essential for the correct folding into the catalytically active conformation, but is crucial for the structural stability of G‐type lysozyme.
Purification and characterization of organellar DNA polymerases in the red alga Cyanidioschyzon merolae
Authors: Moriyama Takashi , Terasawa Kimihiro , Fujiwara Makoto , Sato Naoki
Published: April 2008

DNA polymerase γ, a mitochondrial replication enzyme of yeasts and animals, is not present in photosynthetic eukaryotes. Recently, DNA polymerases with distant homology to bacterial DNA polymerase I were reported in rice, Arabidopsis, and tobacco, and they were localized to both plastids and mitochondria. We call them plant organellar DNA polymerases (POPs). However, POPs have never been purified in the native form from plant tissues. The unicellular thermotrophic red alga Cyanidioschyzon merolae contains two genes encoding proteins related to Escherichia coli DNA polymerase I (PolA and PolB). Phylogenetic analysis revealed that PolB is an ortholog of POPs. Nonphotosynthetic eukaryotes also have POPs, which suggested that POPs have an ancient origin before eukaryotic photosynthesis. PolA is a homolog of bacterial DNA polymerase I and is distinct from POPs. PolB was purified from the C. merolae cells by a series of column chromatography steps. Recombinant protein of PolA was also purified. Sensitivity to inhibitors of DNA synthesis was different in PolA, PolB, and E. coli DNA polymerase I. Immunoblot analysis and targeting studies with green fluorescent protein fusion proteins demonstrated that PolA was localized in the plastids, whereas PolB was present in both plastids and mitochondria. The expression of PolB was regulated by the cell cycle. The available results suggest that PolB is involved in the replication of plastids and mitochondria.
Hatching enzyme of the ovoviviparous black rockfish Sebastes schlegelii– environmental adaptation of the hatching enzyme and evolutionary aspects of formation of the pseudogene
Authors: Kawaguchi Mari , Nakagawa Masahiro , Noda Tsutomu , Yoshizaki Norio , Hiroi Junya , Nishida Mutsumi , Iuchi Ichiro , Yasumasu Shigeki
Published: April 2008

The hatching enzyme of oviparous euteleostean fishes consists of two metalloproteases: high choriolytic enzyme (HCE) and low choriolytic enzyme (LCE). They cooperatively digest the egg envelope (chorion) at the time of embryo hatching. In the present study, we investigated the hatching of embryos of the ovoviviparous black rockfish Sebastes schlegelii. The chorion‐swelling activity, HCE‐like activity, was found in the ovarian fluid carrying the embryos immediately before the hatching stage. Two kinds of HCE were partially purified from the fluid, and the relative molecular masses of them matched well with those deduced from two HCE cDNAs, respectively, by MALDI‐TOF MS analysis. On the other hand, LCE cDNAs were cloned; however, the ORF was not complete. These results suggest that the hatching enzyme is also present in ovoviviparous fish, but is composed of only HCE, which is different from the situation in other oviparous euteleostean fishes. The expression of the HCE gene was quite weak when compared with that of the other teleostean fishes. Considering that the black rockfish chorion is thin and fragile, such a small amount of enzyme would be enough to digest the chorion. The black rockfish hatching enzyme is considered to be well adapted to the natural hatching environment of black rockfish embryos. In addition, five aberrant spliced LCE cDNAs were cloned. Several nucleotide substitutions were found in the splice site consensus sequences of the LCE gene, suggesting that the products alternatively spliced from the LCE gene are generated by the mutations in intronic regions responsible for splicing.
Requirements for chromatin reassembly during transcriptional downregulation of a heat shock gene in Saccharomyces cerevisiae
Authors: Jensen Mette M. , Christensen Marianne S. , Bonven Bjarne , Jensen Torben H.
Published: April 2008

Heat shock genes respond to moderate heat stress by a wave of transcription. The induction phase is accompanied by the massive eviction of histones, which later reassemble with DNA during the ensuing phase of transcription downregulation. In this article, we identify determinants of this reassembly throughout the heat shock protein 104 gene (HSP104) transcription unit. The results show that, although histone H3 lacking amino acids 4–30 of its N‐terminal tail (H3Δ4–30) is normally deposited, reassembly of H3Δ4–40 is obliterated with an accompanying sustained transcription. On mutation of the histone chaperones Spt6p and Spt16p, but not Asf1p, reassociation of H3 with DNA is compromised. However, despite a lasting open chromatin structure, transcription ceases normally in the spt6 mutant. Thus, transcriptional downregulation can be uncoupled from histone redeposition and ongoing transcription is not required to prevent chromatin reassembly.
Low Dielectric Loss PTFE/CeO2 Ceramic Composites for Microwave Substrate Applications
Authors: Anjana Prabhakaran Sreekumari , Sebastian Mailadil Thomas , Suma Memana Narayana , Mohanan Pezholil
Published: April 2008

Cerium oxide (CeO2) filled polytetrafluoroethylene (PTFE) composites prepared by powder processing technique for microwave substrate application is presented in this paper. The PTFE is used as the matrix and the dispersion of CeO2 in the composite is varied up to 0.6 by volume fraction, and the dielectric properties were studied at 1 MHz and microwave frequencies. The relative permittivity and dielectric loss increased with increase in CeO2 content. For 0.6 volume fraction loading of the ceramic, the composite has ɛr of 5 and tan δ of 0.0064 at 7 GHz. Different theoretical approaches have been employed to predict the effective permittivity of composite systems and the results were compared with that of experimental data. The serial mixing model shows good correlation with the experimental results.
Enhanced Tree Recruitment Following Logging in Two Forest Reserves in Ghana
Authors: Swaine Michael D. , Agyeman Victor K.
Published: April 2008

We tested if logging enhances the recruitment of tree species by comparing young tree density in areas disturbed by logging with areas unaffected by logging 6 mo after logging in two Forest Reserves in Ghana. Analysis of 46 commercial timber species showed significantly higher postlogging recruitment in felling gaps and skid trails than in areas unaffected by logging. New seedlings substantially exceeded those lost due to logging operations. Species richness was significantly greater in areas disturbed by logging.
Tap water quality and performance of point‐of‐use treatment devices in Cairo, Egypt
Authors: Smith Edward , El Komos Sally
Published: April 2008

Tap water quality was examined in six sampling events over a 2‐year period in a residential community of Greater Cairo, Egypt. The sampling sites chosen had a granular activated carbon (GAC), reverse osmosis (RO) or distillation point‐of‐use (POU) treatment device so that the performance of these units for standard water quality parameters could be evaluated. Tap water satisfied Egyptian and international drinking water standards and guidelines for the majority of samples analysed. Exceptions were the violation of international limits for lead in 10 samples, and total trihalomethane (TTHM) levels that occasionally exceeded drinking water limits. Only the RO and distillation units achieved removal of total dissolved solids (TDS), alkalinity and hardness. However, GAC units are considerably less costly in the local market. All three POU units exhibited potential reduction of chemical contaminants such as trihalomethanes (THMs), improved taste via chlorine removal and improvement in clarity. Realization of these benefits, however, is conditioned upon proper operation and maintenance of the device.
Adapting Relaxation Techniques to Rural Populations: Implications for High Blood Pressure Therapy*
Authors: Storer John H. , Frate Dennis A. , Banahan Benjamin F. , Johnson Sidney A. , Meydrech Edward F.
Published: April 2008

ABSTRACT: Clinical studies have indicated that inducing the relaxation response through behavior modification can likely lower the blood pressures of hypertensives. However, many of the relaxation techniques commonly used are unsuitable for use in undereducated, isolated, poor, rural, or elderly populations. More suitable techniques were developed for use with these populations in central Mississippi. These simplified techniques were pilot tested on a sample of hypertensives as well as matched hypertensive controls. Over a three month period the systolic blood pressures of the test group were significantly lowered (p=.008) while no significant change occurred in the control group. This paper critiques traditional relaxation techniques as applied to certain populations, describes the simplified techniques used in Mississippi, and presents the results of the trial application. The results suggest that relaxation may help hypertensives control high blood pressure by increasing their ability to cope with the stresses of their therapeutic regimen as well as inducing a direct physiological response.
An Educational Intervention Program for Prevention of Occupational Illness in Agricultural Workers*
Authors: Ferguson Kristi J. , Gjerde Craig L. , Mutel Cornelia , Donham Kelley J. , Hradek Carolyn , Johansen Kay , Merchant James
Published: April 2008

ABSTRACT: This study assessed attitudes, knowledge and behavior related to respiratory health among 198 swine confinement operators, half of whom were assigned to an educational intervention and half of whom served as controls. The project identified significant gaps in knowledge regarding the swine confinement environment and the hazards posed by working in such an environment. Attitudes toward improving the environment were generally favorable, though barriers such as cost and time existed for some confinement operators. An educational program, consisting of six booklets mailed out at two‐week intervals and a group meeting, resulted in significant knowledge gains for the intervention group in areas related to respiratory health and confinement. For example, while fewer than half of the participants recognized on the pretest the recommended levels of potentially hazardous substances such as dust, carbon monoxide, ammonia and hydrogen sulfide, more than 85 percent recognized the recommended levels on the posttest. Evaluations of the units and the group meetings indicate that confinement operators have responded favorably to the project. Follow‐up evaluation is underway to determine whether changes in knowledge have led to changes in behavior.
Impact of changing diet regimes on Steller sea lion body condition
Authors: Atkinson Shannon , Calkins Donald , Burkanov Vladimir , Castellini Michael , Hennen Daniel , Inglis Susan
Published: April 2008

Abstract

A leading theory for the cause of the decline of Steller sea lions is nutritional stress, which led to chronic high juvenile mortality and possibly episodic adult mortality. Nutritional stress may have resulted from either poor quality or low abundance of prey. The objective of this study was to determine whether we could predict shifts in body condition (i.e., body mass or body fat content) over different seasons associated with a change in diet (i.e., toward lower quality prey). Captive Steller sea lions (n= 3) were fed three different diet regimes, where Diet 1 approximated the diet in the Kodiak area in the 1970s prior to the documented decline in that area, Diet 2 approximated the species composition in the Kodiak area after the decline had begun, and Diet 3 approximated the diet in southeast Alaska where the Steller sea lion population has been increasing for over 25 yr. All the animals used in this study were still growing and gained mass regardless of diet. Body fat (%) varied between 13% and 28%, but was not consistently high or low for any diet regime or season. Mean intake (in kg) of Diet 2 was significantly greater for all sea lions during all seasons. All animals did, however, tend to gain less body mass on Diets 2 and 3, as well as during the breeding and postbreeding seasons. They also tended to gain more mass during the winter and on Diet 1, though these differences were not statistically significant. Thus, changing seasonal physiology of Steller sea lions appears to have more impact on body condition than quality of prey, provided sufficient quantity of prey is available. Steller sea lions are opportunistic predators and are evidently able to thrive on a variety of prey. Our results indicate that Steller sea lions are capable of compensating for prey of low quality.
Spatial‐temporal patterns in intra‐annual gray whale foraging: Characterizing interactions between predators and prey in Clayquot Sound, British Columbia, Canada
Authors: Nelson T. A. , Duffus D. A. , Robertson C. , Feyrer L. J.
Published: April 2008

Abstract

In Clayquot Sound, British Columbia, gray whales (Eschrichtius robustus) forage primarily on mysids (FamilyMysideae) and also on crab larvae (FamilyPorcellanidae) that are constrained to specific habitat, which relate to bathymetric depths. In this paper we characterize the interactions of gray whales and their prey by analyzing fine scale spatial‐temporal patterns in foraging gray whale distribution within a season. Kernel density estimators are applied to two seasons (1998 and 2002) of high‐resolution data on foraging by gray whales. By partitioning data from each foraging season into several time periods (12 in 1998 and 11 in 2002), using a temporal autocorrelation function, and generating kernel density estimated surfaces for each time period, it is possible to identify discrete areas of increasing and declining foraging effort. Our results indicate that gray whales forage on mysids throughout a season and opportunistically forage on crab larvae. The episodic crab larvae feeding may reduce, but not eliminate, pressure to mysid populations enabling mysids to reassemble swarms and continue to support gray whale foraging in the latter part of the season. Results suggest that when managing marine environments, gray whale populations require multiple and connected habitats for summer foraging.
Transthyretin Accelerates Vascular Aβ Deposition in a Mouse Model of Alzheimer's Disease
Authors: Wati Henny , Kawarabayashi Takeshi , Matsubara Etsuro , Kasai Ayumi , Hirasawa Takae , Kubota Takeo , Harigaya Yasuo , Shoji Mikio , Maeda Shuichiro
Published: April 2008

Transthyretin (TTR) binds amyloid‐β (Aβ) and prevents Aβ fibril formation in vitro. It was reported that the lack of neurodegeneration in a transgenic mouse model of Alzheimer's disease (AD) (Tg2576 mouse) was associated with increased TTR level in the hippocampus, and that chronic infusion of anti‐TTR antibody into the hippocampus of Tg2576 mice led to increased local Aβ deposits, tau hyperphosphorylation and apoptosis. TTR is, therefore, speculated to prevent Aβ pathology in AD. However, a role for TTR in Aβ deposition is not yet known. To investigate the relationship between TTR and Aβ deposition, we generated a mouse line carrying a null mutation at the endogenous TTR locus and the human mutant amyloid precursor protein cDNA responsible for familial AD (Tg2576/TTR−/− mouse) by crossing Tg2576 mice with TTR‐deficient mice. We asked whether Aβ deposition was accelerated in Tg2576/TTR−/− mice relative to the heterozygous mutant Tg2576 (Tg2576/TTR+/−) mice. Contrary to our expectations, the degree of total and vascular Aβ burdens in the aged Tg2576/TTR−/− mice was significantly reduced relative to the age‐matched Tg2576/TTR+/− mice. Our experiments present, for the first time, compelling evidence that TTR does not suppress but rather accelerates vascular Aβ deposition in the mouse model of AD.