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PubMed1981

Altered calmodulin activity in fluphenazine-resistant mutant strains. Pleiotropic effect on development and cellular organization in Volvox carteri.

Genetically altered calmodulin activity in spontaneously derived mutant strains, which were selected for resistance to the toxic effect of a specific inhibitor, the phenothiazine drug fluphenazine, is demonstrated. Partially purified calmodulin preparations from wild-type and fluphenazine-resistant strains of the multicellular alga Volvox carteri, were tested for the ability to activate Ca2+-ATPase of the erythrocyte membranes, and the inhibition of this stimulatory activity by fluphenazine. Unlike the preparation obtained from wild-type cells, mutant calmodulin is shown to be insensitive to fluphenazine inhibition, in one case, and calmodulin from another strain was found to be inactive in vitro, i.e. it did not activate Ca2+-ATPase. The pleiotropic phenotype of the spontaneously derived mutant strains involved aberrant multicellular organization and hormone-independent commitment of the multipotent asexual reproductive cells, gonodia, to sexual development. These results clearly implicate calmodulin in the control of development and morphogenesis in this simple multicellular eukaryote. In addition, intracellular inhibition of calmodulin in wild-type cells is shown to block the morphogenic process of embryo inversion and to arrest motility. The availability of mutant calmodulin will facilitate further investigation of the role of this ubiquitous regulatory protein in the control of development and differentiation in multicellular eukarytes, as well as the fine structure/function relationship with regard to calmodulin modulation of a wide variety of cellular processes.

Calcium-Binding Proteins↗
PubMed1999

Whatever happened to SRY?

The mammalian sex-determining gene, SRY, was identified by positional cloning approximately 10 years ago. Since its discovery, intense research into this gene has been directed on two main fronts: elucidation of its function in development of the testis and examination of its singular evolutionary history. The role or SRY as the testis-determining factor (TDF) places it at a crucial point in the highly conserved morphogenetic process of vertebrate gonadogenesis. None of the genes that directly activate SRY nor any of its immediate downstream targets have yet been positively identified. Several genes, however, such as SF1, DAX1, and SOX9, whose spatial and temporal expression profiles overlap with that of SRY, are strongly implicated as co-regulators of gonadogenesis. Molecular genetic manipulation of these genes in mice has shown that they are indispensable to sexual development. Remarkably, its key position in this cascade of gene action has not protected SRY from strong yet poorly understood selective forces that have caused it to evolve rapidly in mammals. The evolution of SRY has been characterized not only by rapid sequence divergence within mammals, but also by structural changes such as intron insertion, gene amplification, and deletion.

Amino Acid Sequence↗
PubMedDate not supplied

Growth and maturation of adolescents with idiopathic scoliosis.

The growth and maturation of 409 adolescents with idiopathic scoliosis was prospectively observed and analyzed. Growth of children with scoliosis did not appear to differ from that of their normal peers. However, when measurement of growth was corrected for skeletal age, the children with scoliosis were found to be taller and heavier. Both boys and girls with scoliosis were found to be taller and heavier. Both boys and girls with scoliosis showed a significant tendency for delay in skeletal age (P less than 0.0001), and the girls showed a significant tendency for a delay of puberty (P less than 0.0001). The late skeletal and sexual development observed for the entire series was even more apparent for the girls, for whom spinal curvature exceeded 20 degrees (P less than 0.0001). The authors urge that a menstrual history and a skeletal age determination be included in the initial examination of patients with scoliosis.

Adolescent↗
PubMed2001

Developmentally delimited emergence of more orderly luteinizing hormone and testosterone secretion during late prepuberty in boys.

To quantitate changing feedback control in the GnRH-LH/FSH-testosterone axis in male puberty, we here quantitate the orderliness of hormone release patterns using the regularity (pattern-sensitive) statistic, approximate entropy (ApEn), in 46 eugonadal boys representing 6 genitally defined stages of normal puberty. ApEn is a single variable, model-free, and scale-independent barometer of coordinate signaling or integrative regulation within a coupled neuroendocrine axis. Accordingly, we quantitated ApEn of LH profiles obtained by immunofluorometric assay of sera sampled every 20 min for 24 h. LH ApEn declined remarkably between early prepuberty (genital stage I-A: mean bone age, 4.6 +/- 1.6 yr; testis volume, <3 mL for at least 3 succeeding yr) and late prepuberty (genital stage I-C: bone age, 8.7 +/- 1.8 yr; testis volume, <3 mL for up to 1 yr thereafter; P: = 0.00019), which indicates the acquisition of more regular LH release patterns in late prepuberty. Maximal LH orderliness occurred in puberty stage II (bone age, 10.7 +/- 1.0 yr; testis volume, 2.8 +/- 0.4 mL). The LH secretory process was more disorderly in mid- and later puberty (Tanner stages III and IV). Transpubertal variations in testosterone ApEn manifested a similar tempo, i.e. the greatest regularity of testosterone secretion (lowest ApEn) emerged in Tanner genital stage II (P: < 10(-)(7)), with less orderly patterns evident both earlier and later in sexual development. In contrast, FSH ApEn values remained invariant of pubertal status. Analysis of bihormonal coupling using the theoretically related bivariate cross-ApEn statistic disclosed maximal 2-hormone synchrony for LH and testosterone secretion in genital stage II (P: = 0.031), with relative deterioration of coordinate LH and testosterone release patterns both before and after. LH and FSH release became maximally synchronous at the end of prepuberty (genital stage I-C; P: = 0.029), and FSH and testosterone synchrony peaked in pubertal stage III (P: = 0.037). As mean 24-h serum concentrations of LH, FSH, and testosterone rose transpubertally by 35-fold (LH), 68-fold (FSH), and 70-fold (testosterone), respectively, we infer that pubertal developmental stage per se rather than level of hormone output dictates coordinate GnRH-LH/FSH-testosterone secretion. In summary, in eugonadal boys, the regularity of 24-h LH and testosterone secretory patterns undergoes well defined pubertal stage-specific control. No sexually developmentally delimited regulation is inferable for FSH. The concept of temporally biphasic puberty-dependent variations in neurohormone secretory regularity contrasts with the unidirectional rise in daily hormone output. Accordingly, we infer that late prepuberty and early puberty (Tanner genital stages IC and II) embody a physiologically unique sexual developmental window, marked by transiently enhanced LH and testosterone feedback stability in boys. Whether analogous plasticity of hypothalamo-pituitary-gonadal interactions unfolds during female adolescence is not known.

Child↗
PubMed1987

Treatment of central precocious puberty with an intranasal analogue of GnRH (Buserelin).

One boy and 13 girls with central precocious puberty were treated for 1 year using Buserelin, a GnRH analogue, given intranasally (0.3 mg, four times a day). After 1, 3 and 12 months of therapy, the gonadotropin responses to GnRH were abolished in all the patients whereas mean basal serum concentrations of luteinizing hormone (LH) remained similar to those of pubertal controls. During Buserelin treatment, genital development in the boy and breast development in the girls showed no further progress or some regression. In the boy, serum testosterone levels returned to prepubertal values. In the girls, serum oestradiol levels were variable and, in four of them, vaginal smears showed the persistence of a slight oestrogenic effect during therapy. Pelvic ultrasonography did not show any significant variation in ovarian and uterine lengths. Among the 14 patients, 3 had some progression of pubic hair development, irrespective of serum dehydroepiandrosterone sulphate (DHEAS) levels. In eight patients previously treated with cyproterone, elevated prolactin levels were observed before and during the first month of Buserelin administration. During treatment, mean height velocity was markedly reduced from 11.6 to 6.1 cm/year and mean bone age velocity (+/- 1SD) was 0.85 +/- 0.38 year/year. After 1 year of treatment, the differences in predicted adult height ranged between -0.74 and + 1.04 SDS (standard deviation score). These differences were inversely related (r = -0.72) to the prognosis of adult height calculated before treatment. We conclude that, in central precocious puberty, intranasal administration of Buserelin 1.2 mg/day, may arrest sexual development and reduce height velocity and bone maturation. Improvement of adult height prognosis may occur, especially when it was markedly impaired before treatment.

Administration, Intranasal↗
PubMed2002

Assessing resting heart rate in adolescents: determinants and correlates.

The aim of this study was to evaluate the distribution of resting heart rate and its biological and environmental determinants in adolescents. The study was cross- sectional and the population consisted of 2230 children and adolescents, age range 12-18 years, enrolled randomly from state schools in Turin, Italy. In all participants the following parameters were evaluated: heart rate, blood pressure (BP), weight, height, degree of sexual development, physical activity, parental socio-cultural level. Heart rate and BP were measured after 5, 10 and 15 min in a sitting position. Furthermore, to obtain regression equations to define heart rate as a function of the other variables available, a multiple regression analysis was performed. In both sexes BP, but not heart rate, declined significantly from the first to the last determination. Heart rate was positively and significantly correlated to BP level in both sexes; heart rate was higher in girls (3 bpm) and followed a progressive decreasing trend with age in both sexes, that was opposite to BP values. Age, sexual maturation, height, physical activity and parental socio-cultural level were independent determinants of resting heart rate. In conclusion, resting heart rate in adolescents is related to several methodological, constitutional and environmental factors that have to be taken into account when assessing heart rate values and constructing tables of normal values.

Adolescent↗
PubMed1999

Stimulation of Plasmodium falciparum gametocytogenesis by conditioned medium from parasite cultures.

Plasmodium falciparum gametocyte development was examined in erythrocyte monolayer cultures prepared with Cell-Tak, a cell and tissue adhesive. The monolayers, which were stable for up to 10 days in culture, supported multiple cycles of asexual growth and the development of clusters of stage IV gametocytes. Small numbers of chicken erythrocytes incorporated into the monolayers served as internal reference standards for parasite counts. This permitted quantitative assessment of gametocyte formation under different culture conditions. Gametocyte formation was limited in monolayers grown in standard culture medium but it increased slightly in monolayers cocultured with suspensions of parasitized erythrocytes. The number of gametocytes increased significantly in monolayers grown in parasite-conditioned medium. In both cases the changes resulted from increased numbers of stage II and III gametocytes in the monolayers. These results suggest that parasite conditioned medium contains a factor(s) that stimulates sexual development.

Animals↗
PubMed1993

Assessment of growth and maturation during adolescence.

Clinical techniques currently used to assess adolescent growth and maturation are critically assessed with regard to anthropometric dimensions, measurement reliability, maturity indicators, and growth standards. While anthropometric measurements are virtually standardized throughout the world, a choice of techniques is available for the assessment of skeletal maturity, dental maturity and secondary sexual development. In addition, a variety of charts of international and national reference data are available for the comparison of individuals and groups. These assessment and comparison techniques are contrasted and compared to arrive at a scientifically appropriate set of recommendations for the clinical assessment of growth and maturity during adolescence.

Adolescent↗
PubMed1988

Sex-lethal, a Drosophila sex determination switch gene, exhibits sex-specific RNA splicing and sequence similarity to RNA binding proteins.

The switch gene, Sex-lethal (Sxl), controls sexual development and dosage compensation. It must be active in females and inactive in males throughout development. Analysis of Sxl cDNAs shows that this on/off regulation may be explained by differential RNA splicing; only female transcripts appear to encode functional products, whereas all male transcripts contain an exon that truncates the open reading frame. The functional female product shows sequence similarities with ribonucleoproteins, suggesting that it is an RNA binding protein. Thus, we propose that Sxl encodes a factor that interacts with both its own pre-mRNA (accounting for positive autoregulation) and that of downstream genes to confer female-specific splicing. In this way, a single, simple mechanism could account for both the maintenance and expression of the sexually determined state.

Amino Acid Sequence↗
PubMed2005

Plasmodium berghei: effect of protease inhibitors during gametogenesis and early zygote development.

Plasmodium berghei: The effect of five protease inhibitors, TPCK, TLCK, PMSF, leupeptin, and 1,10-phenanthroline on in vitro gametogenesis and early zygote development of P. berghei was investigated. PMSF and leupeptin showed no effect. Cysteine/serine protease inhibitors TPCK/TLCK at concentrations of 75 and 100 microM were effective on inhibiting exflagellation center formation, and this effect was reversible with the addition of l-cysteine. Exflagellation center formation was most effectively blocked by 1,10-phenanthroline (1mM), and exflagellation center numbers were restored by the addition of Zn(2+). A reduction of ookinete production was observed when TPCK/TLCK (100 microM) was added at 2h after gametogenesis, but no effect was observed with 1,10-phenanthroline (1mM). Our results suggest that proteolysis is important in both gametocyte activation and sexual development of P. berghei.

Analysis of Variance↗
PubMed2002

The adolescent thalassemic. The complicant rebel.

Chronic hereditary conditions are expected to have a strong influence on the psychosocial development of the adolescent. Thalassaemia major is the commonest of these disorders in Mediterranean countries. In the past it was rarely seen in adolescence because the majority of patients died in childhood. The availability of treatment has allowed survival but the optimum treatment is difficult, especially chelation which consists of daily subcutaneous infusions of 10 hours duration. The adolescent patient must achieve social independence while he/she has a dependency on family, doctors and nurses and a need to strictly adhere to a difficult regime. Non-adherence will result in complications and possible fatality. Family and caretakers may become overprotective. Short stature, bone deformities and poor sexual development influence self image and self confidence. The purpose of this paper is to examine how various published studies have viewed the adolescent with Thalasaemia and to draw conclusions about the necessity for supportive services for the patients and their families. Earlier studies gave emphasis to negative psychosocial trends such as dysphoric moods, dependency, low self esteem, fears, anxiety etc. These were attributed to family stresses and over-protectiveness as well as the condition. Other studies from centers in Italy mainly, have demonstrated normal psychosocial development with better social adjustment than normal peers. Recently published data suggest that Italian patients are more compliant to treatment compared to Greek and Cypriot patients. This may be due to better psychosocial support. The need for such support is emphasized as is the need for training of doctors and nurses dealing with Thalassaemia major patients.

Adolescent↗
PubMed2004

The Pho80-like cyclin of Aspergillus nidulans regulates development independently of its role in phosphate acquisition.

In Saccharomyces cerevisiae, phosphate acquisition enzymes are regulated by a cyclin-dependent kinase (Pho85), a cyclin (Pho80), the cyclin-dependent kinase inhibitor Pho81, and the helix-loop-helix transcription factor Pho4 (the PHO system). Previous studies in Aspergillus nidulans indicate that a Pho85-like kinase, PHOA, does not regulate the classic PHO system but regulates development in a phosphate-dependent manner. A Pho80-like cyclin has now been isolated through its interaction with PHOA. Surprisingly, unlike PHOA, An-PHO80 does play a negative role in the PHO system. Similarly, an ortholog of Pho4 previously identified genetically as palcA also regulates the PHO system. However, An-PHO81, a putative cyclin-dependent kinase inhibitor, does not regulate the PHO system. Therefore, there are significant differences between the classic PHO system conserved between S. cerevisiae and Neurospora crassa compared with that which has evolved in A. nidulans. Most interestingly, under low phosphate conditions, the An-PHO80 cyclin also promotes sexual development while having a negative effect on asexual development. These effects are independent of the role An-PHO80 has in the classic PHO system. However, in high phosphate medium, An-PHO80 affects development because of deregulation of the PHO system as loss of palcA(Pho4) function negates the developmental defects caused by lack of An-pho80. Therefore, under low phosphate conditions the An-PHO80 cyclin regulates development independently of the PHO system, whereas in high phosphate it affects development through the PHO system. The data indicate that a single cyclin can control various aspects of growth and development in a multicellular organism.

Amino Acid Sequence↗
PubMed2003

Glia-to-neuron signaling and the neuroendocrine control of female puberty.

The sine qua non event of puberty is an increase in pulsatile release of gonadotrophin hormone releasing hormone (GnRH). It is now clear that this increase and, therefore, the initiation of the pubertal process itself, require both changes in transsynaptic communication and the activation of glia-to-neuron signaling pathways. While neurons that utilize excitatory and inhibitory amino acids as transmitters represent major players in the transsynaptic control of puberty, glial cells utilize a combination of trophic factors and small cell-cell signaling molecules to regulate neuronal function and, thus, promote sexual development. A coordinated increase in glutamatergic transmission accompanied by a decrease in inhibitory GABAergic tone appears to initiate the transsynaptic cascade of events leading to the pubertal increase in GnRH release. Glial cells facilitate GnRH secretion via cell-cell signaling loops mainly initiated by members of the EGF and TGF- families of trophic factors, and brought about by either these factors themselves or by chemical messengers released in response to growth factor stimulation. In turn, a neuron-to-glia communication pathway mediated by excitatory amino acids serves to coordinate the simultaneous activation of transsynaptic and glia-to-neuron communication required for the advent of sexual maturity. A different--and perhaps higher--level of control may involve the transcriptional regulation of subordinate genes that, by contributing to neuroendocrine maturation, are required for the initiation of the pubertal process.

Animals↗
PubMed2006

Activation of zoosporogenesis-specific genes in Phytophthora infestans involves a 7-nucleotide promoter motif and cold-induced membrane rigidity.

Infections of plants by the oomycete Phytophthora infestans typically result from zoospores, which develop from sporangia at cold temperatures. To help understand the relevant cold-induced signaling pathway, factors regulating the transcription of the zoosporogenesis-specific NIF (nuclear LIM-interactor-interacting factor) gene family were examined. Sequences required for inducing PinifC3 were identified by analyzing truncated and mutated promoters using the beta-glucuronidase reporter in stable transformants. A 7-nucleotide (nt) sequence located 139 bases upstream of the major transcription start point (GGACGAG) proved essential for the induction of PinifC3 when sporangia were shifted from ambient to cold temperatures. The motif, named the cold box, also conferred cold inducibility to a promoter normally activated only during sexual development. An identical motif was detected in the two other zoosporogenesis-specific NIF genes from P. infestans and three Phytophthora sojae orthologues, and a closely related sequence was found in Phytophthora ramorum orthologues. The 7-nt motif was also found in the promoters of other zoosporogenesis-induced genes. The presence of a cold box-interacting protein in nuclear extracts of P. infestans sporangia was demonstrated using electrophoretic mobility shift assays. Furthermore, zoospore release and cold box-regulated transcription were stimulated by the membrane rigidizer dimethyl sulfoxide and inhibited by the membrane fluidizer benzyl alcohol. The data therefore delineate a pathway in which sporangia perceive cold temperatures through membrane rigidity, which activates signals that drive both zoosporogenesis and cold-box-mediated transcription.

Amino Acid Motifs↗
PubMed1998

Body image and psychopathology in adolescence: a controlled clinical study.

The aim of this study was to investigate mentally disturbed adolescents' problems of acknowledging and accepting the physical changes and sexual maturation of their bodies, in comparison with healthy adolescents. The study sample consisted of 60 adolescents (30 boys and 30 girls), 15-18 years of age, who had been referred for psychiatric examination, and 60 healthy controls, matched on the basis of age, sex, place of residence and level of education. The study methods were the self-rated questionnaire and psychiatric in-depth interview modified on the basis of the diagnostic profile of adolescents. Mentally disturbed adolescents had more negative attitudes towards developmental body changes than healthy adolescents. They were unable to describe the physical changes they had undergone. Healthy adolescents were more aware of developing sexual characteristics. On discriminant analysis, independent background variables explaining problems relating to sexual maturation in mentally disturbed adolescents were found to be a lack of or low number of peer relationships, and long-term stress. In the healthy adolescents, independent variables associated with problems in sexual maturation were found to be a lack of or low number of peer relationships and a single-parent home. We conclude that adolescents with psychiatric problems seem to have a poorer capacity to process mentally the ongoing bodily and sexual maturation of their bodies than matched healthy controls.

Adaptation, Psychological↗
PubMed1986

The gonadotropic-axis involvement in the course of the filial following response in the domestic fowl chick.

The detachment process of the domestic chick from its mother, or any other imprinting object occurs between the sixth and tenth week after hatching. The present study (Experiment I), examines whether the detachment process parallels endocrine events that precede prepuberty. Immediately upon hatching, groups of heavy strain chicks were imprinted to a colored foam rubber ball for 72 hours. The bond between these chicks and the imprinting object was then tested, and plasma LH and testosterone were assayed once a week until the chicks were 10 weeks of age; the sexual development of chicks of the same strain was studied at the same time. At the outset of the detachment period (5-7 weeks) an increase in plasma testosterone and a decrease in plasma LH was found. In addition, the comb and testes showed a definite weight increase while the bursa of Fabricius showed a significant decline in weight. In Experiment II, the beginning of the detachment process was induced by injecting 3 to 4 week old chicks with testosterone-propionate, estradiol-benzoate and 5 alpha-dihydrotestosterone. Our evidence therefore appears to demonstrate that testosterone and its metabolites induce the detachment process by the same mechanism used to stimulate sexual behavior in juvenile chicks.

Animals↗
PubMed1983

Performance of layers reared and/or kept under different 6-hour light-dark cycles.

Using 60 hens reared and kept on a standard lighting programme (decreasing followed by increasing photoperiod to 22 weeks of age and 14 h continuous light: 10 h continuous dark during lay) as control, the effects of the following intermittent patterns on development and performance were studied. Group 1. The same rearing programme, followed by, between 20 and 36 weeks, 3 h light (L):3 h dark (D) intermittent and then from 36 weeks a regime in which each light period was progressively shortened by 30 min every 8 weeks with corresponding lengthening of the dark period so that the last cycle used between 52 and 60 weeks was 1.5 h L:4.5 h D. Group 2.6-hour light-dark cycles from hatching; the light:dark ratio first decreasing and then increasing, such that total light hours per day varied as in the control group to 20 weeks, and then subsequent lighting as in 1. Group 3. Intermittent lighting of 1.5 h L:4.5 h D unvaryingly from 4 to 60 weeks. Sexual development was essentially the same in all groups. Egg numbers were decreased slightly by the short light-dark cycles but daily egg mass output was the same in all groups. Food utilisation was best in group 1 and worst in the control group. In general egg weight and shell quality were improved by the short light-dark cycles; the effect appearing with the first eggs and being especially marked for group 3. On intermittent regimes ovipositions were equally distributed, between the four daily light-dark periods when the light:dark ratio was near unity but were more numerous during the first half of the solar day when the ratio was 1.5 L:4.5 D.

Animals↗
PubMed1977

Overnight gonadotropin excretion in normal females.

FSH and LH in acetone precipitates of timed overnight urine collections were measured by radioimmunoassay. FSH and LH urinary excretion extrapolated to 24 h was determined in 140 normal girls 3-16 years. Timed overnight urines were collected throughout a menstrual cycle from 3 normal adult women. FSH and LH progressively increased with age from 2.0 +/- 0.5 (FSH) and 2.0 +/- 0.4 (LH) IU/24 h for the 3--4 yr age group to 8.1 +/- 1.8 (FSH) and 11.5 +/- 3.8 (LH) IU/24 h for the 15--16 yr age group. Mean FSH and LH excretion for succeeding age groups (3--4, 5--6, 7--8, 9--10, 11--12, 13--14 and 15--16 years) increased significantly for the 5--6, 9--10 and 11--12 year age groups. Mean LH but not FSH excretion increased significantly for the 13--14 year age group. FSH and LH excretion increased progressively with stage of sexual development. In the 3 girls with established menstrual cycles. FSH (43.6 +/- 5.0 IU/24 h) and LH (113.7 +/- 7.8 IU/24 h) peaks occurred on the same day. Luteal phase excretion of FSH and LH was significantly lower than follicular phase excretion. Timed overnight urine collection allows integration of several hours of FSH and LH excretion.

Adolescent↗