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Biomedical subjects

A Reich

Publications and source records attributed to A Reich.

At least 37 records · Page 2Linked to original sources
PubMed2003

Expression of chicken 75-kDa gelatinase B-like enzyme in perivascular chondrocytes suggests its role in vascularization of the growth plate.

UNLABELLED: A newly cloned avian 75-kDa gelatinase B-like enzyme is expressed by the cells surrounding the blood vessels of the growth plate and upregulated by angiogenic substances in cultured chondrocytes. Despite its low homology to mammalian gelatinase-B, the avian 75-kDa seems to function similarly in the context of endochondral bone formation. INTRODUCTION: Gelatinase B/metalloproteinase (MMP)-9, a zinc-dependent protease of the MMP family, is a key regulator in the final step of endochondral ossification. Recently an avian 75-kDa gelatinase B-like enzyme that shows low sequence similarity to the mammalian enzyme (59% on the protein level) was cloned and characterized. However, its expression pattern in the chicken growth plate and its role in bone formation have not, so far, been examined. RESULTS: Based on the published sequence, we cloned a 700-bp fragment from cDNA of the chicken growth plate and studied its expression pattern in primary chondrocytes. Because the basal expression level of gelatinase B was almost undetectable, we induced its expression by different culturing conditions, the most dramatic induction achieved by treatment with retinoic acid, which is known as an inducer of vascular invasion in the epiphyseal plates. The gelatinolitic activity, checked by zymography, detected bands corresponding to the gelatinase A and B as well as a new high-molecular weight band of approximately 200 kDa. We further studied the expression pattern of gelatinase B by in situ hybridization. The gelatinase B was expressed by the cells surrounding the blood vessels penetrating the growth plate and by chondrocytes located in the front of these vascular invasions in the borders between the bone and the cartilage, resembling the expression of mouse gelatinase B in the growth plate. The induction of rickets by a vitamin D-deficient diet reduced the expression levels of gelatinase B in the growth plate of 12-day-old chickens but did not affect the expression of gelatinase A mRNA. CONCLUSION: The chicken growth plate has a distinctly different structure from the mammalian one: it is much wider, it contains more cells in each zone, and the blood vessels penetrate deeper into the hypertrophic zone. Nevertheless, the upregulation of the avian 75-kDa gelatinase B-like enzyme by vitamins A and D, coupled with its perivascular expression pattern in the growth plate, implies a similar role for the mammalian and avian genes in bone formation.

Animals↗
PubMed2001

Clinical aspects of obesity in childhood and adolescence--diagnosis, treatment and prevention.

The level of fatness at which morbidity increases is determined on an acturial basis. Direct measurements of body fat content, eg hydrodensitometry, bioimpedance or DEXA, are useful tools in scientific studies. However, body mass index (BMI) is easy to calculate and is frequently used to define obesity clinically. An increased risk of death from cardiovascular disease in adults has been found in subjects whose BMI had been greater than the 75th percentile as adolescents. Childhood obesity seems to increase the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge on the role of neuropeptides such as POMC, neuropeptide Y (NPY) and the melanocyte concentrating hormone receptors (MC4R). Environmental/exogenous factors contribute to the development of a high degree of body fatness early in life. Twin studies suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders including a number of endocrine disorders (Cushing's syndrome, hypothyroidism, etc) and genetic syndromes (Prader-Labhard-Willi syndrome, Bardet-Biedl syndrome etc) that can present with obesity. A simple diagnostic algorithm allows for the differentiation between primary or secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia and psychosocial problems. Therapeutic strategies include psychological and family therapy, lifestyle/behavior modification and nutrition education. The role of regular exercise and exercise programs is emphasized. Surgical procedures and drugs used as treatments for adult obesity are still not recommended for children and adolescents with obesity. As obesity is the most common chronic disorder in the industrialized societies, its impact on individual lives as well as on health economics has to be recognized more widely. This review is aimed towards defining the clinical problem of childhood obesity on the basis of current knowledge and towards outlining future research areas in the field of energy homoeostasis and food intake control.

Adolescent↗
PubMed2001

Clinical aspects of obesity in childhood and adolescence.

The level of fatness of a child at which morbidity acutely and/or later in life increases is determined on an acturial basis. Direct measurements of body fat content, e.g. hydrodensitometry, bioimpedance, or DEXA, are useful tools in scientific studies. However, body mass index (BMI) is easy to calculate and is generally accepted now to be used to define obesity in children and adolescents clinically. An increased risk of death from cardiovascular disease in adults has been found in subjects whose BMI had been greater than the 75th percentile as adolescents. Childhood obesity seems to substantially increase the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge on the role of neuropeptides such as POMC, neuropeptide Y (NPY) and the melanocyte concentrating hormone receptors (for example, MC4R). Environmental/exogenous factors largely contribute to the development of a high degree of body fatness early in life. Twin studies suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders including a number of endocrine disorders (Cushing's syndrome, hypothyroidism, etc.) and genetic syndromes (Prader-Labhard-Willi syndrome, Bardet Biedl syndrome, etc.) that can present with obesity. A simple diagnostic algorithm allows for the differentiation between primary or secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia, back pain and psychosocial problems. Therapeutic strategies include psychological and family therapy, lifestyle/behaviour modification and nutrition education. The role of regular exercise and exercise programmes is emphasized. Surgical procedures and drugs used in adult obesity are still not generally recommended in children and adolescents with obesity. As obesity is the most common chronic disorder in industrialized societies, its impact on individual lives as well as on health economics has to be recognized more widely. This review is aimed towards defining the clinical problem of childhood obesity on the basis of current knowledge and towards outlining future research areas in the field of energy homoesostasis and food intake in relation to child health. Finally, one should aim to increase public awareness of the ever increasing health burden and economic dimension of the childhood obesity epidemic that is present around the globe.

Adolescent↗
PubMed2001

The DSL analog free testosterone assay: serum levels are not related to sex hormone-binding globulin in normative data throughout childhood and adolescence.

In this study we tested the performance of easy-to-use and rapid, commercially available immunoassays to measure free testosterone (fT) and sex hormone-binding globulin (SHBG). We asked whether fT and SHBG serum levels are age-dependent and whether or not there is a gender dependence of fT and SHBG in this age group. Finally, by measuring fT and SHBG in sera of a cohort of healthy children and adolescents using commercially available immunoassays, we established normative data for fT and SHBG in this age group: in boys fT levels increased significantly (r=0.83, p<0.0001) from 0.63 pmol/l (median) in the age group below 5 years to 56.9 pmol/l in the age group 16-20 years. In girls fT levels also increased with age (r=0.66, p<0.0001): from 0.72 pmol/l (median) in the age group below 5 years to 3.34 pmol/l in the age group 16-20 years. In contrast, SHBG serum concentrations significantly decreased with age in boys (r=-0.62, p<0.0001) but remained constant in girls (r=0.04, n.s.). Importantly, fT values were independent of SHBG levels as determined by our methods. In conclusion, fT can be measured in an acceptable quality using the DSL analog tracer-based immunoassay and normative data are now available. In addition, SHBG levels in healthy children and adolescents are also given and may permit for studies of pathophysiologic states in this age group.

Adolescent↗
PubMed2001

Obesity in childhood and adolescence: clinical diagnosis and management.

The industrialized countries around the world are experiencing an epidemic of childhood obesity. The level of fatness of a child at which morbidity increases acutely and/or later in life is determined on an individual basis. Overall, however, childhood obesity substantially increases the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge of the role of neuropeptides such as pro-opiomelanocortin, neuropeptide Y and the melanocyte-concentrating hormone receptors. Environmental and exogenous factors are the main contributors to the development of a high degree of body fatness early in life. Studies involving twins suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders, including a number of endocrine disorders, such as Cushing's syndrome and hypothyroidism, and genetic syndromes, such as Prader-Labhard-Willi syndrome and Bardet-Biedl syndrome, that can present with obesity. A simple diagnostic algorithm allows for differentiation between primary and secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia, back pain and psychosocial problems. It is somewhat ironic that the definition of obesity in childhood is not an easy one. Direct measurements of body fat content, such as hydrodensitometry, bioimpedance, or dual-energy X-ray absorptiometry, are useful tools in scientific studies. Body mass index (BMI) is, however, now generally accepted to be a good clinical measure for the definition of obesity in children and adolescents. In preadolescent boys, BMI also relates to muscle mass and should be used for the definition of fat mass with great caution. An increased risk of death from cardiovascular disease in adults has been found in patients whose BMI had been greater than the 75th percentile as adolescents. Therapeutic strategies include psychological and family therapy, modification of lifestyle and behavior, and nutritional education. The role of regular exercise and exercise programs is emphasized, while surgical procedures and drugs used in adult obesity are still not generally recommended for obese children. Obesity is the most common chronic disorder in industrialized countries, and its impact on individual lives as well as on health economics must be recognized by physicians and the public alike. This review aims to increase awareness of the health burden and economic dimension of the epidemic of childhood obesity that is occurring around the globe.

Adolescent↗
PubMed2000

Immune down-regulation and peripheral deletion of CD8 T cells does not require TNF receptor-ligand interactions nor CD95 (Fas, APO-1).

TNF receptor-ligand interactions and CD95 (Fas / APO-1) have been demonstrated to be involved in activation-induced death of mature T cells. Here, we examined the role of these molecules in the murine model of lymphocytic choriomeningitis virus (LCMV) infection using LCMV TCR transgenic (tg) mice lacking TNF, TNF receptor I (TNFR1), CD95 or both TNFR1 and CD95. This report demonstrates that neither TNF receptor-ligand interactions nor CD95 was required for down-regulation of LCMV-specific CD8 T cells following acute LCMV infection in vivo. Even LCMV-specific CD8 T cells lacking both TNFR1 and CD95 molecules declined after the acute phase of the infection with normal kinetics. Furthermore, peripheral deletion of LCMV-specific CD8 T cells induced by LCMV peptide injection or by adoptive transfer of tg spleen cells expressing the corresponding LCMV epitope was not impaired in mice lacking TNF, TNFR1 and / or CD95. Our data speak against an indispensable role of these molecules in antigen-induced apoptosis of CD8 T cells in vivo and suggest that T cell homeostasis after antigen challenge is controlled by additional mechanisms.

Animals↗
PubMed2000

Autotransfusion and blood-sparing techniques in infants and children.

While several techniques to reduce perioperative blood loss have been established for surgery in adults, not all of them are applicable in paediatric surgery. Further, far less is known about the efficacy of these techniques in this specific population. Consequently, techniques for the prevention of blood loss are often neglected. However, it is these young patients, with their remaining life expectancy, who will benefit the most from any prevented infection (HIV, hepatitis, etc.) or from any immunological complications. Hemodilution is limited because of the high percentage of fetal hemoglobin in small infants, as well as the additional anaesthetic needed to obtain blood. Until recently, intraoperative autotransfusion was ineffective in small children due to technical limitations; however, advanced technology now renders intraoperative autotransfusion possible, even in infants weighing less than 20 kg.

Journal Article↗
PubMed2000

Biological characterisation of superficial bladder cancer by bivariate cytokeratin 7/DNA analysis, flow cytometric assessment of MIB- 1, and an immunohistochemical study.

A total of 238 cases of bladder carcinoma stages Ta, Tis, T1 were submitted prospectively to multiparameter flow cytometry and immunohistochemical study in order to determine the biological aggressiveness of the tumour. DNA index (DI), S-phase fraction (SPF) obtained by bivariate cytokeratin 7/DNA analyses, and the immunohistochemical evaluation of p53 and MIB-1 were studied in relation to the traditional prognostic factors in bladder cancer (stage and grade). the variance analysis results showed that DNA aneuploidy was significantly associated with high stage (p = 0.0001), high grade (p = 0.0001), high SPF value > or = 5.5% (p = 0.0001), MIB-1 positivity > or = 31% (p = 0.0001) and high expression of p53 (staining involving > 50% of cells, p = 0.0001). Even if there was no statistical significance the hypotetraploid class (1.70 < DI < 1.89) showed poor prognostic biomarkers more frequently than the other aneuploid classes. Out of 238 cases, 101 were also submitted to flow cytometric measurement of MIB-1 (fMIB-1) to study the correlation between cell proliferation and DNA content. Data obtained from fresh, 3:1 methanol/acetone fixed samples were compared with values obtained from both cell cycle analysis methods and routine application of the MIB-1 immunostaining in histological sections. fMIB-1 values were positively correlated with SPF values (r = 0.801, p < 0.01) and S+G2M fraction (percentage of cells in S and in G2M phases) (r = 0.763, p < 0.01) but no correlation with paraffin sections was found. A fMIB-1 value > 7% was strongly associated with aneuploidy (p = 0.0001). The determination of DNA content coupled with the study of the epithelial (cytokeratin 7) and proliferative (MIB-1) markers could be useful in providing important information on the biological behaviour of superficial bladder tumours.

Adult↗
PubMed2000

Cortisol and 17-hydroxyprogesterone levels in saliva of healthy neonates: normative data and relation to body mass index, arterial cord blood ph and time of sampling after birth.

The measurement of cortisol and 17-hydroxyprogesterone (17-OHP) in saliva has become a reliable tool for both the scientist and the clinician for studying adrenal cortical function in the adult and the older child. We have now established in parallel normative data for salivary cortisol and 17-OHP levels in healthy neonates. We have asked whether or not there is a circadian rhythm of cortisol and 17-OHP saliva levels in neonates. Furthermore, we have asked whether salivary hormone levels correlated with auxologic and clinical data and time of sampling. Cortisol and 17-OHP levels in saliva samples from 119 healthy neonates (55 girls, 64 boys) were measured using in-house time-resolved fluorescent immunoassays. Saliva samples were obtained using a saliva collecting tube three times a day on the first or second day of life. Gender and gestational age did not influence salivary cortisol and 17-OHP levels. No significant circadian rhythm of salivary hormone levels was detected in this group of newborns. However, body mass index, arterial cord blood pH and time of saliva sampling significantly influenced salivary hormone levels. In conclusion, measurement of cortisol and 17-OHP in saliva is feasible in healthy neonates. The existence of normative data forms the basis for future studies on pathophysiologic states in the newborn period.

17-alpha-Hydroxyprogesterone↗
PubMed2000

Body fat mass, leptin and puberty.

Leptin, the ob gene product, provides a molecular basis for the lipostatic theory of the regulation of energy balance. Leptin circulates as a monomeric 16 kDa protein in rodent and human plasma and is also bound to leptin binding proteins that may form large high molecular weight complexes. Initial models of leptin action included leptin-deficient ob/ob mice and leptin-insensitive db/db mice. Peripheral or central administration of leptin reduced body weight, adiposity, and food intake in ob/ob mice but not in db/db mice. In ob/ob mice leptin treatment restored fertility. Leptin interacts with many messenger molecules in the brain. For example, leptin suppresses neuropeptide Y (NPY) expression in the arcuate nucleus. Increased NPY activity has an inhibitory effect on the gonadotropin axis and represents a direct mechanism for inhibiting sexual maturation and reproductive function in conditions of food restriction and/or energy expenditure. By modulating the hypothalamo-pituitary-gonadal axis both directly and indirectly, leptin may thus serve as the signal from fat to the brain about the adequacy of fat stores for pubertal development and reproduction. Normal leptin secretion is necessary for normal reproductive function to proceed and leptin may be a signal allowing for the point of initiation of and progression toward puberty.

Adipose Tissue↗
PubMed1999

The Drosophila STAM gene homolog is in a tight gene cluster, and its expression correlates to that of the adjacent gene ial.

Drosophila STAM is a homolog of mammalian STAM genes, which encode Jak associated signal-transducing adapter molecules. A 20-kilobase stretch of genomic DNA at 32B on chromosome arm 2L, which contains Drosophila STAM, has been sequenced. By comparison to cDNAs isolated and characterized, this region contains four tightly clustered genes: ial, mitochondrial porin, and the two newly discovered genes, STAM and DNZ1. Like its mouse and human homologs, STAM bears SH3 and ITAM domains. DNZ1 is a founding member of a sub-family of proteins bearing a DHHC/NEW1 zinc finger domain. Although these four genes are contained in a defined Deficiency overlap interval, no available P-element mutations in the region disrupt any of the genes, and no other discrete mutations in the genes have been identified. Among the four genes, ial and STAM share a common 5' control region, suggesting coordinate expression. Developmental Northern data and embryonic and ovariole expression data show that STAM and ial expression are correlated. The other two genes in the cluster appear to be expressed at constitutive levels throughout development.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Lipophilic antioxidants in blood plasma as markers of atherosclerosis: the role of alpha-carotene and gamma-tocopherol.

Oxidative theory of atherosclerosis implies that plasma levels of lipophilic antioxidants might serve as indicators of lipoprotein oxidation in the arterial wall and as markers of the development of atherosclerosis. However, it is unknown whether the measurement of plasma antioxidants is able to reflect atherogenesis or its risk. In order to assess whether the levels of lipophilic antioxidants in human plasma can discriminate between subjects with and without atherosclerosis, we measured the lipophilic antioxidants alpha-tocopherol, gamma-tocopherol, alpha-carotene, beta-carotene and ubiquinol-10 in plasma of 34 patients with coronary heart disease (CHD) and in 40 control subjects. We found that alpha-carotene and gamma-tocopherol were significantly lower in plasma of CHD patients compared to controls. This decrease was significantly independent of whether the antioxidants were expressed as its absolute amounts in plasma (P < 0.001 for alpha-carotene, and P = 0.001 for gamma-tocopherol) or normalized to plasma lipids (P < 0.001 for both). In contrast, beta-carotene was only lower in plasma of CHD patients in comparison to controls, when normalized to the lipids (P = 0.02). Independent contributions of different parameters to the variation in these plasma antioxidants were estimated using multiple regression approach. The analysis showed that both the decrease in alpha-carotene and the decrease in gamma-tocopherol were significantly associated only with the presence of CHD (P < 0.001 for each regression), while the decrease in beta-carotene was significantly related to the presence of hyperlipidaemia (P < 0.001). In striking contrast, no decrease in plasma alpha-tocopherol and ubiquinol-10 was detected in the patient group independently of how these antioxidants were expressed. These data suggest that plasma levels of alpha-carotene and gamma-tocopherol may represent markers of atherosclerosis in humans. Measuring these antioxidants may be of clinical importance as a practical approach to assess atherogenesis and/or its risk.

Adult↗
PubMed1999

Cloning, mapping, and expression of ial, a novel Drosophila member of the Ipl1/aurora mitotic control kinase family.

The members of the Ipl1-aurora like kinase (IARK) subfamily are conserved serine/threonine kinases that play a key role in the control of chromosome segregation, centrosome separation, and cytokinesis from yeast to mammals. We report on the isolation of a new Drosophila member of the family, designated Ipl1-aurora-like kinase (ial) Phylogenetic analysis of kinase domains established that ial is more divergent from known mammalian IARKs than is aurora. Mapping based on examination of chromosomal aberrations, together with mapping within contigs identified by the Drosophila Genome Project, placed the gene at 32B on the left arm of the second chromosome. Discrete single-gene mutations in this region, including all known relevant P-element disruptions, were examined and proven not to be mutations in ial. Characterization of spatial and temporal expression of ial and its gene product showed that it manifests itself in patterns which can be consistent with a role in cell cycle control.

Amino Acid Sequence↗
PubMed1999

A role for leptin in sexual maturation and puberty?

Leptin, the ob gene product, is involved in the regulation of body weight in rodents, primates and humans. It provides a molecular basis for the lipostatic theory of the regulation of energy balance. White adipose tissue and placenta are the main sites of leptin synthesis. There is also evidence of ob gene expression in brown fat. Leptin seems to play a key role in the control of body fat stores by coordinated regulation of feeding behaviour, metabolic rate, autonomic nervous system regulation and body energy balance. Apart from the function of leptin in the central nervous system on the regulation of energy balance, it may well be one of the hormonal factors that signal to the brain the body's readiness for sexual maturation and reproduction. During late pregnancy and at birth when maternal fat stores have been developed, leptin levels are high. During these developmental stages leptin could be a messenger molecule signalling the adequacy of the fat stores for reproduction and maintenance of pregnancy. At later stages of gestation leptin could signal the expansion of fat stores in order to prepare the expectant mother for the energy requirements of full-term gestation, labour and lactation. Leptin serum concentrations change during pubertal development in rodents, primates and humans. In girls, leptin serum concentrations increase dramatically as pubertal development proceeds. The pubertal rise in leptin levels parallels the increase in body fat mass. In contrast, leptin levels increase shortly before and during the early stages of puberty in boys and decline thereafter. Testosterone has been found to suppress leptin synthesis by adipocytes both in vivo and in vitro. The decline of leptin levels in late puberty in boys accompanies increased androgen production during that time and most likely reflects suppression of leptin by testosterone and a decrease in fat mass and relative increase in muscle mass during late puberty in males. This overview focuses on those topics of leptin research which are of particular interest in reproductive and adolescent medicine.

Animals↗
PubMed1999

Sprouty is a general inhibitor of receptor tyrosine kinase signaling.

Sprouty was originally identified as an inhibitor of Drosophila FGF receptor signaling during tracheal development. By following the capacity of ectopic Sprouty to abolish the pattern of activated MAP kinase in embryos, we show that Sprouty can inhibit other receptor tyrosine kinase (RTK) signaling pathways, namely the Heartless FGF receptor and the EGF receptor. Similarly, in wing imaginal discs, ectopic Sprouty abolishes activated MAP kinase induced by the EGF receptor pathway. Sprouty expression is induced by the EGFR pathway in some, but not all, tissues in which EGFR is activated, most notably in follicle cells of the ovary, the wing imaginal disc and the eye disc. In the ovary, induction of sprouty expression follows the pattern of EGFR activation in the follicle cells. Generation of homozygous sprouty mutant follicle-cell clones demonstrates an essential role for Sprouty in restricting EGFR activation throughout oogenesis. At the stage when dorso-ventral polarity of the follicle cells is established, Sprouty limits the ventral expansion of the activating Gurken signal. Later, when dorsal appendage fates are determined, reduction of signaling by Sprouty facilitates the induction of inter-appendage cell fates. The capacity of Sprouty to reduce or eliminate accumulation of activated MAP kinase indicates that in vivo it intersects with the pathway upstream to MAP kinase. The ability of ectopic Sprouty to rescue lethality caused by activated Raf suggests that it may impinge upon the pathway by interacting with Raf or downstream to it.

Animals↗