High-Resolution Infrared Spectrum of CD(3)CN: Analysis of the Interacting nu(3) and nu(6) Bands and Evaluation of the A(0) Constant.

The infrared spectrum in the range 900-1230 cm(-1) including the fundamental bands nu(3) and nu(6) of CD(3)CN has been studied. The resolution attained was 0.0025 cm(-1) in the measurement on the Bruker 120 HR Fourier spectrometer in Oulu. About 4000 lines were assigned in the nu(6) band. For the weak nu(3) band, which has not been observed earlier directly, we were able to assign 206 lines in three subbands K=8-10. These lines become detectable due to the strong nu(3)/nu(6) Coriolis resonance. There is also an l(1,-2) resonance between nu(3) and nu(6), which made it possible to obtain a value 2.647721(50) cm(-1) for the axial rotational constant A(0), when D(0)(K) from force field calculations was applied. Different types of resonances with the overtone 3nu(8) and the combinations nu(4)+nu(8) and nu(7)+nu(8) were observed. A fit with a standard deviation of 0.0019 cm(-1) was attained by using a model of 10 different resonances. Copyright 2001 Academic Press.

Rotational Analysis of the Ground State and the Lowest Fundamentals nu(3), nu(5), and nu(6) of (13)CH(3)D.

The nu(3), nu(5), and nu(6) fundamental bands of the (13)CH(3)D molecule have been studied with Fourier transform infrared spectroscopy. The spectra and results for the parent species (12)CH(3)D (O. N. Ulenikov, G. A. Onopenko, N. E. Tyabaeva, J. Schroderus, and S. Alanko, J. Mol. Spectrosc. 193, 249-259 (1999)) have been used to assign and analyze about 1900 lines belonging to the (13)CH(3)D isotopic species. About 850 ground state combination differences with DeltaK = 0 were calculated, which allowed us to determine the J-dependent ground state rotational constants. The K-dependent constants as well as those describing the a(1)-a(2) (K = 3) splitting were fixed to the values obtained for the (12)CH(3)D species. The (v(3) = 1), (v(5) = 1), and (v(6) = 1) states were fit simultaneously by including the intervibrational interactions in the Hamiltonian. The rotational energies, the rotational and centrifugal distortion constants, as well as the resonance parameters involving the three states have been determined and discussed. Copyright 2000 Academic Press.

Higher concentrations of serum transferrin receptor in children than in adults.

BACKGROUND: The serum transferrin receptor (TfR) concentration in adults is suggested to provide a sensitive measure of iron depletion and together with the serum ferritin concentration to indicate the entire range of iron status, from iron deficiency to iron overload. However, little is known about TfR concentrations in children. OBJECTIVE: Our objective was to compare serum TfR and ferritin concentrations and their ratios in children and adults and look for correlations between TfR concentrations and other measures of iron status. DESIGN: Our study groups were healthy 1-y-old infants (n = 36), 11-12-y-old prepubertal boys (n = 35), and 20-39-y-old men (n = 40). RESULTS: TfR concentrations were higher in infants (x; 95% reference interval: 7.8 mg/L; 4.5, 11.1) than in prepubertal boys (7.0 mg/L; 4.7, 9.2) and higher in prepubertal boys than in men (5.8 mg/L; 3.1, 8.5). Geometric mean TfR-ferritin ratios were higher in infants (316; 95% reference interval: 94, 1059) than in prepubertal boys (219; 78, 614) and higher in prepubertal boys than in men (72; 23, 223). By multiple linear regression analysis, the best predictors of TfR concentration were serum iron (P = 0.004) and log serum ferritin (P < 0.0001), both being inverse correlations (R2 = 0.32). Mean corpuscular volume, blood hemoglobin, transferrin iron saturation, transferrin, and even age seemed to not have an influence on the TfR concentration and erythropoiesis was not a determinant of TfR concentration. CONCLUSIONS: Low serum ferritin and iron concentrations, even within the normal physiologic range, result in high TfR concentrations. The lower the iron stores, the stronger the influence of ferritin on TfR. A high TfR concentration in children, especially in infants, is a response to physiologically low iron stores. Age-specific reference concentrations for TfR are needed.

Isotope Substitution in near Local Mode Molecules: Bending Overtones nnu2 (n = 2, 3) of the HDS Molecule.

There are two main goals in the present study: (a) to record and analyze the weak overtones nnu2 (n = 2, 3) of the bending fundamental nu2 of the HDS molecule and (b) to derive new isotopic relations for spectroscopic parameters applicable to predict, at least qualitatively, the structures of the excited bending states of HDX-type molecules. Copyright 1998 Academic Press.

First High-Resolution Study of the 13CHD3 Infrared Spectrum: Rotational Analysis of the Ground State and the Fundamentals nu5 and nu3/nu6.

The rotational structure in three fundamental bands nu3, nu5, and nu6 of 13CHD3 has been analyzed. As this study evidently is the first high-resolution investigation on the spectrum of this molecule, the determination of the ground state rotational constants was the necessary first step. The nu5 band (1290.536 cm-1) could be treated as an isolated band whereas it was necessary to analyze the bands nu3 (994.713 cm-1) and nu6 (1030.243 cm-1) simultaneously because of very strong interactions. The total number of assigned lines was 1116. The spectral region 850-1530 cm-1 was measured on a Fourier transform spectrometer and the 13C species was in natural abundance in CHD3. Copyright 1998 Academic Press.

Biphasic increase in serum inhibin B during puberty: a longitudinal study of healthy Finnish boys.

We investigated the concentrations of serum inhibin B and the pro-alphaC-containing inhibins (pro-alphaC inhibin) and their relations to serum FSH levels in 38 healthy boys during their progression through puberty. Furthermore, we studied the effect of recombinant human FSH (rhFSH) on pro-alphaC inhibin production in three prepubertal gonadotropin-deficient boys. The serum inhibin B level increased between Tanner stages G1 and G2 (p < 0.02), simultaneously with the serum LH and testosterone concentrations. In advanced puberty, inhibin B changed less, and at stage G4, correlated negatively with serum FSH level (r = -0.57, p < 0.001, n = 37). The serum pro-alphaC inhibin level changed differently and increased also in advanced puberty. In prepubertal healthy subjects, the serum pro-alphaC inhibin and FSH levels correlated positively (r = 0.50, p = 0.051, n = 16), and during the rhFSH treatment of gonadotropin-deficient boys, serum pro-alphaC inhibin levels increased. These findings suggest that an increased production of inhibin B is an early event in puberty and that inhibin B can inhibit pituitary FSH secretion in the course of sexual maturation. Furthermore, they suggest that during puberty free inhibin (pro)-alpha-subunits, detected by the pro-alphaC inhibin assay, are present in large amounts and that FSH stimulates their production by prepubertal testes.

High-Resolution Fourier Transform Spectra of HDS in the Regions of the Bands nu1 and 2nu1/nu2 + nu3

High-resolution spectrum of the HDS molecule was recorded with the Bruker Fourier spectrometer in Oulu in the regions of the nu1 and 2nu1/nu2 + nu3 absorption bands. Fine rotational structure of the nu1 band was analyzed with the model of an isolated vibrational state, while in the analysis of the 2nu1 and nu2 + nu3 bands it was necessary to take into account the resonance interactions between these two bands. Comparison of the experimentally determined parameters is made with the deductions of the expanded local mode approach. Copyright 1998 Academic Press.

Serum markers of collagen metabolism and serum osteocalcin in relation to pubertal development in 57 boys at 14 years of age.

We investigated whether levels of serum collagen markers and serum osteocalcin are related to pubertal growth and development in a cross-sectional study of 57 healthy boys at 14 y of age. The level of the soft tissue marker, serum amino-terminal propeptide of type III procollagen (PIIINP) was higher in boys at Tanner stages G3 versus G2 (p < 0.01). The levels of the markers of bone collagen matrix differed only at a more advanced pubertal stage: the formation markers, carboxy-terminal and amino-terminal propeptides of type I procollagen, and the degradation marker, carboxy-terminal telopeptide of type I collagen were higher only at stage G4 versus G3 (p < 0.01). The marker of bone mineralization, serum osteocalcin was also higher only at stage G4 versus G3 (p < 0.01). Stage G4 was associated with the pubertal growth spurt. The results demonstrate that pubertal development should be taken into account when serum levels of collagen markers and osteocalcin are evaluated, and suggest that an increase in serum PIINP in boys at G3 might predict a normal pubertal growth spurt, but the finding remains to be confirmed in longitudinal studies.

Body iron stores decrease in boys during pubertal development: the transferrin receptor-ferritin ratio as an indicator of iron status.

The transferrin receptor in serum provides a useful measure of tissue iron deficiency and the rate of erythropoiesis, whereas serum ferritin reflects the amount of storage iron in normal subjects. We studied the serum transferrin receptor and the transferrin receptor-ferritin ratio in 57 healthy prepubertal or early pubertal boys and followed them at 3-mo intervals for 24 mo to evaluate their iron status during puberty. The mean laboratory parameters changed as follows: Hb from 13.0 to 13.3 g/dL (p = 0.01), mean corpuscular volume from 85 to 84 fL (p = 0.0001), transferrin receptor from 6900 to 7200 micrograms/L (p = 0.03) ferritin from 36 to 23 micrograms/L (p = 0.0001), and transferrin receptor-ferritin ratio from 230 to 400 (p = 0.0001). At the start of the investigation, the serum transferrin receptor was elevated (> 9000 micrograms/l) or ferritin low (< = or 12 micrograms/L) in fewer than 2% of the boys. During the subsequent 2 y the proportion of boys with an elevated transferrin receptor or low ferritin value increased. The two parameters were simultaneously abnormal in none of the boys initially, but in about 3% of the boys 2 y later. The change in transferrin receptor-ferritin ratio was closely correlated with genital development. The proportion of elevated transferrin receptor-ferritin ratios increased 4.5-fold during the 2 y, indicating the high responsiveness of the ratio. At the end of the study, iron therapy was started to eliminate any iron deficiency. In response to the therapy, the mean transferrin receptor-ferritin ratio fell to 210 +/- 19, i.e. close to the level at the beginning of the study. The marked responses of the transferrin receptor and the receptor-ferritin ratio to iron therapy reflect the dependence of these parameters on iron status rather than on physiologic differences in the rate of erythropoiesis.

Body iron stores in relation to growth and pubertal maturation in healthy boys.

During male puberty, erythropoiesis is exceptionally active. Pubertal development and iron status were followed in 60 healthy boys at 3-month intervals for 24 months to evaluate changes in body iron stores with the serum transferrin receptor-ferritin ratio. The estimated amount of stored iron declined by about 50% over a 2-year period. Remarkable changes in iron stores were found even after as short an interval as 3 months and pubertal development was closely linked with a decrease in stored iron. The annual increments of estimated red blood cell (RBC) iron showed strong positive correlations with velocities in testicular volume and certainly in body height and weight. In contrast, the estimated changes in individual iron stores were not associated with any of those parameters. The lacking associations between iron stores and growth parameters are probably indicative of increasing intestinal absorption. Despite the relatively small quantitative role of iron stores in supplying iron for growth, falling iron stores probably play a more important regulatory role by stimulating iron absorption.

A New Rotational Study of the Ground Vibrational State of CHD3

A careful rotational analysis of the ground vibrational state of the CHD3 molecule is made on the basis of the ground state combination differences method using, as the initial information, transitions from 12 infrared absorption bands: nu3(A1), nu6(E), nu5(E), 2nu3(A1), 2nu6(A1), 2nu6(E), nu3 + nu6(E), 2nu5(A1), 2nu5(E), nu3 + nu5(E), nu5 + nu6(A1 + A2), and nu5 + nu6(E). More than 2500 "forbidden" transitions were used to determine the parameters C, DK, and HK. a1 - a2 (K = 3) splittings in the ground vibrational state were found and analyzed. Copyright 1997 Academic Press. Copyright 1997Academic Press

Precise Study of the Lowest Vibration-Rotational Bands nu5 and nu3/nu6 of the CHD3 Molecule

The high-resolution absorption spectrum of the CHD3 molecule has been measured on a Fourier transform spectrometer in the region of the nu5 and nu3/nu6 bands and analyzed for the first time by taking into account a1 - a2 (K = 3) splittings of the ground vibrational state. The problem of ambiguity in determining the corresponding epsilon; parameter of the ground vibrational state was solved on the basis of the analysis of the rotational structure of the nu5 band. Numerous a1-a2 splittings for the states with Kupper = 1, 2, 4, 5, 7 in the nu5 and nu6 bands are described. Copyright 1997 Academic Press. Copyright 1997Academic Press

The High-Resolution Fourier Transform Spectrum of Dideuterated Methane CH2D2 in the Region between 1900 and 2400 cm-1

The infrared spectrum of doubly deuterated methane CH2D2 has been recorded in the region from 1900 to 2400 cm-1 at almost Doppler-limited resolution by using two high-resolution Fourier transform spectrometers. The vibrational bands observed include 2nu4, nu4 + nu7, 2nu7, nu2, nu8, nu4 + nu9, and nu7 + nu9, which were analyzed by taking into account Coriolis and Fermi interactions among them and also those with nu4 + nu5, nu3 + nu7, and nu5 + nu7. Most of the centrifugal distortion constants were constrained to appropriate values, while the vibrational term value and three rotational constants in each of the seven excited states were adjusted along with Coriolis and Fermi interaction parameters by the least-squares analysis of the observed spectrum. The vibration-rotation interaction constants alphas thus determined for the nu2 and nu8 states were combined with those of other fundamental states already published to calculate the equilibrium C-H distance.

The role of luteinizing hormone-beta gene polymorphism in the onset and progression of puberty in healthy boys.

An immunologically anomalous LH with two point mutations in its beta-subunit gene (Trp8Arg and Ile15Thr) has recently been described. This polymorphism is common in Finland; 28% of the population are homo- or heterozygous for the variant allele. To assess the effect of the LH variant on LH action, we correlated its presence in a group of 49 healthy boys with the onset and progression of puberty. This group was followed-up longitudinally from a mean age of 11.7 +/- 0.1 yr for 3 yr at 3-month intervals. In addition, we studied the prevalence of the variant LH in boys with constitutional pubertal delay (testicular volume < or = 4 mL after 13.5 yr of age). The LH beta gene status of each subject in this study was judged from a single venous blood sample using two immunofluorometric LH assays with different combinations of monoclonal antibodies: one detecting both the variant and wild-type LH, and the other detecting only wild-type hormone. Of the boys with pubertal onset at a normal age, 36 (74%) were homozygous for the wild-type LH beta allele, 12 (24%) were heterozygous, and 1 (2%) was homozygous for the variant LH beta allele. Clear differences in pubertal parameters were found between the boys with normal and mutated (homo- or heterozygous) LH genotypes. During the follow-up, the boys with the mutated genotype had smaller testicular volumes (P < 0.03), were shorter (P < 0.02), had slower growth rates (P < 0.04), and had lower serum insulin-like growth factor I-binding protein-3 levels (P < 0.03) than the boys with the normal LH genotype. In the boys with delayed onset of puberty, the frequency of the variant LH beta allele did not differ from that in the reference population, indicating that the variant LH is not associated with conditions due to disturbed control of the reactivation of GnRH secretion. We conclude that during the progression of puberty, the variant LH may be less active in stimulating testicular growth than wild-type LH. Thus, the gene may affect tempo, contributing to the wide normal variation in pubertal progression in healthy boys. Our results also suggest that the variant LH not only affects the course of puberty, but is already involved in the regulation of the GH-insulin-like growth factor I axis during childhood.

Quality of life in early adolescence: a sixteen-dimensional health-related measure (16D).

While data on the health-related quality of life (HRQOL) of adults are accumulating, very little is known about the HRQOL--and especially the perceived HRQOL--of children. In our study we introduced a 16-dimensional, generic self-assessment measure of HRQOL (16D) for early adolescents, and demonstrated its use with four populations of children aged 12-15: (1) 239 normal schoolchildren, (2) patients waiting for organ transplantation (n = 5), (3) patients with genetic skeletal dysplasias (n = 19), and (4) patients with epilepsy (n = 32). The HRQOL profiles of the patients differed significantly according to the diagnosis, giving support to its construct validity. The reliability of the measure was high: its repeatability coefficient was 91%. The quality of life ratings of the healthy boys and their parents differed on the dimensions of distress, vitality, speech, mental function, and discomfort and symptoms (p < 0.05). In addition, there were significant differences in the health-related valuations between the girls, boys and their parents. We conclude that the assessment of quality of life of adolescents should be based on data collected from the adolescents themselves. Further, the 16D is so far the only generic HRQOL measure designed specifically for this purpose. It is capable of differentiating the HRQOL of healthy adolescents as well as patients with various diagnoses. Our experience also indicates that it is easy to use, yet it seems comprehensive, reliable, and valid.

Development of iron status and response to iron medication in pubertal boys.

During male puberty, rapid growth of body mass and the rise in hemoglobin concentration require much iron. The increasing need for iron may carry a risk of iron deficiency. Criteria for iron deficiency in adolescence are difficult to assess, as indicated by prevalences ranging from 0.5 to 30% in five recent studies from developed countries. We followed 60 prepubertal or early pubertal boys, testing them at 6-month intervals for 24 months and relating hemoglobin levels and other iron parameters to age, pubertal development, and response to iron medication. A significant increase in mean hemoglobin was first seen at genital stage G4. In early puberty, in contrast, between stages G1 and G3, ferritin decreased. Mean transferrin increased slightly during the study. The prevalence of iron deficiency increased both with age and with advancing puberty. However, the early decline in ferritin may be a physiologic response to guarantee increasing intestinal absorption. After iron medication, we observed improvements in the levels of our parameters of iron status, which showed that hemoglobin levels had been limited by iron deficiency. In pubertal boys, evaluation of iron deficiency should not be based on laboratory parameters alone; age, pubertal development, and growth should also be taken into account.

Serum transferrin and ferritin in pubertal boys: relations to body growth, pubertal stage, erythropoiesis, and iron deficiency.

We studied serum transferrin and ferritin concentrations in relation to individual body growth, stage of puberty, blood hemoglobin, and red blood cell iron (RBCI) in 60 prepubertal or early pubertal boys at 3-mo intervals for 18 mo. One-third of the boys had increased serum transferrin concentrations and almost all had decreased ferritin concentrations during the followup. No change in mean transferrin was observed but the individual 18-mo increments in transferrin correlated positively with the increments in hemoglobin (r = 0.55, P < 0.001) and in estimated RBCI (r = 0.31, P = 0.02). Serum transferrin remained stable at different genital stages, but ferritin was lower in the pubertal than in the prepubertal boys. Transferrin concentrations at 18 mo correlated positively with the preceding weight velocities. The rise in transferrin did not lead to an increase in iron-deficiency anemia. In contrast, transferrin rose in boys whose hemoglobin increased. In pubertal boys with relatively ample iron status, serum transferrin may be an indicator of increased availability of iron for erythropoiesis. The declining ferritin concentration indicates that part of the extra iron is mobilized through redistribution from stores to red blood cell mass and is generally associated with greatly increasing absorption. Thus, the pubertal changes in transferrin and ferritin are not necessarily indications of iron deficiency.

Sensitive immunoassay and in vitro bioassay demonstrate constant bioactive/immunoreactive ratio of luteinizing hormone in healthy boys during the pubertal maturation.

The quality of serum LH was assessed during pubertal maturation in boys by measuring immunoreactive (I) LH by a time-resolved immunofluorometric assay (IFMA, Delfia), and bioactive (B) LH by a sensitized in vitro bioassay. Seven samples were collected at 3-mo intervals from 14 healthy boys (median starting age 11.8 y) during pubertal maturation from Tanner stage I-III or II-IV (n = 7 for each). The mouse Leydig cell in vitro bioassay was sensitized 10-fold, to 0.05-0.1 IU/L, by including 1.5 mumol/L of forskolin in the incubation medium. The I- and B-LH levels showed good linear correlation throughout the concentration range analyzed. Mean I-LH increased between the pubertal stages I-IV from 0.42 to 2.24 IU/L and that of B-LH from 1.35 to 5.04 IU/L. No concomitant change occurred in the B-LH/I-LH (B/I) ratio, which was 2.84 +/- 0.54 in stage I and 2.58 +/- 0.48 in stage IV (mean +/- SEM, n = 7). Although the B/I ratios of LH varied from 0.59 to 5.85 in the samples analyzed, the intraindividual variation was small (mean coefficient of variance, 22%). In conclusion, IFMA and sensitized in vitro bioassay showed in healthy boys a similar 4-5-fold increase in the mean LH concentration during pubertal maturation, with no concomitant change in the B/I ratio. The sensitized in vitro bioassay of LH is useful for analysis of the low peripubertal LH levels. The good correlation between the I-LH and B-LH levels, and the lack of change in LH B/I ratio, indicate that IFMA correctly estimates the LH levels upon evaluation of pubertal maturation.

Insulin-like growth factor I and insulin-like growth factor binding protein 3 as determinants of blood hemoglobin concentration in healthy subjects.

We studied the serum concentrations of IGF-I, IGF-binding protein 3 (IGFBP-3), and testosterone in relation to blood Hb in 60 healthy prepubertal or early pubertal boys twice, with a 9-mo interval. Serum IGF-I and testosterone levels were measured by RIA, and serum IGFBP-3 was measured by monoclonal immunofluorometric assay. Positive correlations were observed between the concentrations of blood Hb and serum IGF-I at the first examination (r = 0.36, p = 0.008) and Hb and IGFBP-3 at both examinations (r = 0.53, p < 0.001, and r = 0.39, p = 0.003). No association between Hb and testosterone concentrations was found. Our results show that blood Hb is positively correlated to serum IGF-I and IGFBP-3 levels, indicating indirectly the involvement of growth hormone in the regulation of physiologic Hb concentration. Because no association was found between Hb and testosterone concentrations, this may indicate that the role of androgens in erythropoiesis may be different at different stages of puberty. It is concluded that the IGF system may be involved in the rise of Hb level during early puberty.

Serum transferrin receptor for assessment of iron status in healthy prepubertal and early pubertal boys.

A recently introduced test measures the concentration of transferrin receptor (TfR) in serum, which increases shortly after the onset of iron deficiency. In adults this increase reflects the degree to which tissue iron availability is impaired. We developed a fluoroimmunoassay to quantify TfR. The purpose of this study was to evaluate the role of TfR as an index of iron sufficiency in 62 healthy prepubertal or early pubertal boys. The mean concentration of serum TfR was 3.8 (-1 SEM = 3.6, +1 SEM = 3.9) mg/L. No associations were observed between the serum TfR and the concentration of Hb, the values of packed cell volume, reticulocyte production index, mean corpuscular Hb, mean corpuscular volume, or the concentrations of serum iron, transferrin, or ferritin. Because none of the subjects had signs of iron deficiency, we determined the 95% reference intervals for Hb, red blood cell indices, and the above-mentioned serum concentrations. The reticulocyte count and reticulocyte production index were higher than expected. Our results indicated that the individual concentration of TfR in serum does not depend on any of the several other parameters of iron status in a group of healthy individuals.