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61.
Carlos R Ferreira Dillon Kavanagh Ralf Oheim Kristin Zimmerman Julian Stürznickel Xiaofeng Li Paul Stabach R Luke Rettig Logan Calderone Colin MacKichan Aaron Wang Hunter A Hutchinson Tracy Nelson Steven M Tommasini Simon von Kroge Imke AK Fiedler Ethan R Lester Gilbert W Moeckel Björn Busse Thorsten Schinke Thomas O Carpenter Michael A Levine Mark C Horowitz Demetrios T Braddock 《Journal of bone and mineral research》2021,36(5):942-955
Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
62.
63.
Rachel Vanderkruik Lianne Gonsalves Grace Kapustianyk Tomas Allen Lale Say 《Bulletin of the World Health Organization》2021,99(5):359
ObjectiveTo systematically review the literature on the mental health of adolescents associated with sexual and reproductive outcomes, and compare the mental health outcomes with that of other age groups.MethodsWe searched seven databases for relevant peer-reviewed articles published between 1 January 2010 and 25 April 2019. Our inclusion criteria required that the study included age-disaggregated data on adolescents, and focused and assessed mental health outcomes associated with pregnancy or sexually transmitted infections. We extracted data on the specific health event, the mental health outcome and the method of measuring this, and comparisons with other age groups.FindingsAfter initially screening 10 818 articles by title and abstract, we included 96 articles in our review. We observed that a wide-ranging prevalence of mental ill-health has been reported for adolescents. However, most studies of mental health during pregnancy did not identify an increased risk of depression or other mental disorders among adolescents compared with other age groups. In contrast, the majority of studies conducted during the postpartum period identified an increased risk of depression in adolescents compared with other age groups. Three studies reported on mental health outcomes following abortion, with varying results. We found no studies of the effect of sexually transmitted infections on mental health among adolescents.ConclusionWe recommend that sexual and reproductive health services should be accessible to adolescents to address their needs and help to prevent any adverse mental health outcomes. 相似文献
64.
Brodin L Theordorsson E Christenson J Cullheim S Hökfelt T Brown JC Buchan A Panula P Verhofstad AA Goldstein M 《The European journal of neuroscience》1990,2(12):1095-1109
Neurotensin (NT)-like peptides in the CNS of the lamprey Lampetra fluviatilis were studied by radioimmunoassay (C-terminal specific NT antiserum), reverse-phase HPLC and immunohistochemistry. Multiple peaks of NT-immunoreactive (-ir) material were observed upon HPLC, of which a major peak eluted in the position of bovine NT. Immunofluorescence histochemistry showed that a monoclonal antibody recognizing the N-terminal (1 - 11) fragment of NT, as well as two polyclonal NT antisera labelled a large number of cell bodies in the periventricular area of hypothalamus, including the postinfundibular commissural nucleus and the ventral and dorsal hypothalamic nuclei. Additional groups of NT-ir cells were observed in the preoptic nucleus, the postoptic commissural nucleus, the mesencephalic tegmentum (L.fluviatilis), and in the spinal cord (L.fluviatilis and Ichtyomyzon unicuspis). Dense NT-ir fibre plexuses were present in the caudal hypothalamus, corpus striatum, ventral mesencephalon, and in the dorsal horn and lateral margin of the spinal cord. At the ultrastructural level the lateral spinal margin showed NT-ir terminal structures, which in most cases were not associated with synaptic specializations, although occasional synaptic contacts with unlabelled elements were found. The relation between NT-ir and monoamine-containing cells was examined with immunofluorescence double-staining, using antisera to tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), and histamine respectively. In the periventricular nuclei of hypothalamus numerous TH-, 5-HT-, as well as histamine-ir cells were located in close association with NT-ir cells, but none of the aminergic markers could be detected within NT-ir neurons. The chemical properties as well as the anatomical distribution of lamprey NT-like peptides show several similarities with those present in mammals, suggesting that NT-containing neuronal systems in the CNS developed early in vertebrate phylogeny. 相似文献
65.
The value of cancer treatment was assessed using a natural experiment where patients who refused treatment served as no-treatment controls in a situation where withholding treatment to form a control group is unethical. Each cancer patient who refused treatment in Alberta, Canada between 1975 and 1988 was compared with five subjects who accepted treatment, matched on cancer site, age, number of cancers, and time period. Variables associated with treatment-refusal were included in Cox's proportional hazards model of survival, with death from cancer as the endpoint and deaths from other causes as censored observations. Treatment was refused at a rate of 7.5 per 1,000. One-third of patients who refused treatment had lung cancer and most had unstaged disease. Treatment refusal was associated with a difference in median survival of approximately nine months. Site-specific analyses showed a range of effects. Case fatality among the treated patients fell by approximately 10 percent during the 14-year study period. Even in advanced disease, treatment can result in improved survival. However, the results of this study must be interpreted with caution and cannot be generalized to all cancer patients.Dr Huchcroft and Mr Snodgrass are with the Alberta Cancer Board, Calgary, Alberta, Canada. Address correspondence to Dr Shirley Huchcroft, Senior Scientist, Division of Epidemiology and Preventive Oncology, Alberta Cancer Board, Calgary, Alberta, Canada T2N 4N2. 相似文献
66.
Jana Jedlickova Marie Vajter Tomas Barta Graeme C. M. Black Rahat Perveen Jan Mares Marek Fichtl Bohdan Kousal Lubica Dudakova Petra Liskova 《Clinical genetics》2023,104(4):418-426
Four members of a three-generation Czech family with early-onset chorioretinal dystrophy were shown to be heterozygous carriers of the n.37C>T in MIR204. The identification of this previously reported pathogenic variant confirms the existence of a distinct clinical entity caused by a sequence change in MIR204. Chorioretinal dystrophy was variably associated with iris coloboma, congenital glaucoma, and premature cataracts extending the phenotypic range of the condition. In silico analysis of the n.37C>T variant revealed 713 novel targets. Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants. Haplotype analysis excluded relatedness with the original family reported to harbour the n.37C>T variant in MIR204. Identification of a second independent family confirms the existence of a distinct MIR204-associated clinical entity and suggests that the phenotype may also involve congenital glaucoma. 相似文献
67.
Lipoteichoic acids (LTAs) of pathogenic and apathogenic Listeria species and of Staphylococcus aureus were fractionated and tested for their ability to stimulate production of cytokines (IL-1α, IL-6, TNF-α) in resident peritoneal
macrophages (Mϕ) of endotoxin-resistant C3H/HeJ mice using a serum-free medium. For IL-1α and IL-6 there were no detectable
differences in the ability of LTA fractions of pathogenic and apathogenic Listeria species and of Staphylococcus aureus. However, LTA-2 fractions of Staphylococcus aureus, which might be less hydrophobic than the LTA-2 fractions of the listeriae-induced lower amounts of TNF-α. Furthermore, the
more lipophilic LTA-2 fractions of all LTAs employed were more potent inducers of cytokines than the less lipophilic LTA-1
fractions. The biologic effect of LTAs appears, therefore, to depend mainly on their hydrophobicity. 相似文献
68.
Zeller W Schafer B Benz A Gutensohn K Becker K Fiedler W Hossfeld D 《Oncology reports》1994,1(2):411-414
Monoclonal antibodies Leu 11a (CD16) and Leu 19 (CD56) were tested for reactivity with cells from 36 patients with acute myelogenous leukemia (AML) using two-colour flow cytometry. Blast cells were identified by a broad panel of monoclonal antibodies. In 33% (12/36) the monoclonal antibody Leu 19, which has been demonstrated to bind to the 140 kD isoform of the human neural cellular adhesion molecule N-CAM, found on peripheral natural killer (NK)-cells, neuroectodermal cells, activated T-cells, and myeloma cells, was shown to bind strongly to the leukemic cells. The monoclonal antibody Leu 11a, which recognizes a surface differentiation antigen associated with the low affinity FcRIII for IgG, expressed on NK-cells, granulocytes and macrophages were found to bind to leukemic cells of four of the 12 Leu-19 positive cases. 50% (6/12) of Leu-19 positive patients were classified as having M4 according to the French-American-British (FAB) morphology criteria. The potential diagnostic and clinical importance of CD 56 and/or CD 16 expression in acute myelogenous leukemia is presently under investigation. 相似文献
69.
Fiedler W Dahse R Schlichter A Junker K Kosmehl H Ernst G Schubert J Claussen U 《International journal of oncology》1996,9(6):1227-1232
Telomerase activity and telomere length were analyzed in a total of 59 surgically removed primary renal cell carcinoma (RCC). The study includes tissue from the centre of the tumor, several different peripheral tumor areas, metastases and secondary tumors. None of the normal renal cortex tissues used as control exhibited telomerase activity. In contrast, telomerase activity was detected in 55 out df 59 (=93%) tested primary RCC. There was no case with intratumoral heterogeneity concerning the telomerase activity status. All metastases and secondary tumors were telomerase-positive. In the four telomerase deficient tumors all measured telomeric repeat fragments were shortened in comparison to the normal tissue. As these patients exhibit no metastases or secondary tumors a less malignant variant of RCC is supposed. There was no correlation between telomerase activity and specific histopathological subtypes of RCC or specific chromosomal aberrations. As telomerase activity is not associated with advanced stages of tumors it may be an important early event in the development of RCC. Thus, telomerase activity may be a prevalent marker for early and late stages of all subtypes of RCC. 相似文献
70.
John C. Norman Clifford C. Dacso George J. Reul Edward K. Massin Tomas Klima Barry D. Kahan John T. Reiser Denton A. Cooley 《Artificial organs》1978,2(4):413-420
The abdominal left ventricular assist device (ALVAD) is an order of magnitude more effective than conventional intra-aortic balloon pumping (IABP) in unloading and providing circulatory support to the failing left ventricle. This is a report of a unique case which demonstrates that in the absence of pulmonary vascular obstruction or constriction, the ALVAD can substitute for both left and right heart function. A 21-year-old patient with a congenital bicuspid aortic valve developed acute valvular endocarditis which rapidly progressed to congestive heart failure. An operation was undertaken, the mitral and aortic valves were excised and replaced by porcine heterografts, and a fistula from the right sinus of Valsalva to the right ventricle was closed. When coronary circulation was restored, irreversible ischemic contracture of the left ventricle, or "stone heart" syndrome, developed and emergency ALVAD or partial artificial heart implantation was effected. This device functioned as a total artificial heart for nearly six days, while a donor heart was sought. The patient then underwent removal of the ALVAD and cardiac and renal allografting. The transplanted heart functioned well, but the patient expired fifteen days later from gram-negative sepsis. 相似文献