Impediments to effective fertility reduction. Contraception should be moved out of the hands of doctors.
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Contraception↗
Biomedical subjects
T Black
Publications and source records attributed to T Black.
Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand.
A receptor that mediates osteoprotegerin ligand (OPGL)-induced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cDNA library and is identical to the tumor necrosis factor receptor (TNFR) family member RANK. The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo. Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo. Furthermore, polyclonal Ab against the RANK extracellular domain promotes osteoclastogenesis in bone marrow cultures suggesting that RANK activation mediates the effects of OPGL on the osteoclast pathway. These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells.
Animals↗
Inflammatory cytokines and vascular endothelial growth factor stimulate the release of soluble tie receptor from human endothelial cells via metalloprotease activation.
Activation of endothelial cells, important in processes such as angiogenesis, is regulated by cell surface receptors, including those in the tyrosine kinase (RTK) family. Receptor activity, in turn, can be modulated by phosphorylation, turnover, or proteolytic release of a soluble extracellular domain. Previously, we demonstrated that release of soluble tie-1 receptor from endothelial cells by phorbol myristate acetate (PMA) is mediated through protein kinase C and a Ca2+-dependent protease. In this study, the release of soluble tie-1 was shown to be stimulated by inflammatory cytokines and vascular endothelial growth factor (VEGF), but not by growth factors such as basic fibroblast growth factor (bFGF) or transforming growth factor alpha (TGFalpha). Release of soluble tie by tumor necrosis factor alpha (TNFalpha) or VEGF occurred within 10 minutes of stimulation and reached maximal levels within 60 minutes. Specificity was shown by fluorescence-activated cell sorting (FACS) analysis; endothelial cells exhibited a significant decrease in cell surface tie-1 expression in response to TNF, whereas expression of epidermal growth factor receptor (EGF-R) and CD31 was stable. In contrast, tie-1 expression on megakaryoblastic UT-7 cells was unaffected by PMA or TNFalpha. Sequence analysis of the cleaved receptor indicated that tie-1 was proteolyzed at the E749/S750 peptide bond in the proximal transmembrane domain. Moreover, the hydroxamic acid derivative BB-24 demonstrated dose-dependent inhibition of cytokine-, PMA-, and VEGF-stimulated shedding, suggesting that the tie-1 protease was a metalloprotease. Protease activity in a tie-1 peptide cleavage assay was (1) associated with endothelial cell membranes, (2) specifically activated in TNFalpha-treated cells, and (3) inhibited by BB-24. Additionally, proliferation of endothelial cells in response to VEGF, but not bFGF, was inhibited by BB-24, suggesting that the release of soluble tie-1 receptor plays a role in VEGF-mediated proliferation. This study demonstrated that the release of soluble tie-1 from endothelial cells is stimulated by inflammatory cytokines and VEGF through the activation of an endothelial membrane-associated metalloprotease.
Amino Acid Sequence↗
Testing the potential of sodium fluoride to affect spermatogenesis: a morphometric study.
This study provides quantitative information on the effect of sodium fluoride (NaF) on the testes of F1 generation male rats exposed in utero and during lactation to NaF at one of four concentrations (25, 100, 175, 250 ppm). At weaning, the F1 generation males were exposed to NaF in their drinking water for 14 weeks, after which time testicular tissues were perfusion-fixed with glutaraldehyde and observed after being embedded in plastic. The seminiferous tubules comprised 89%, 87%, 88%, 88% and 88% of the total testis volume while the interstitial space occupied 9.3%, 11.2%, 10.2%, 9.8% and 9.9% of the total testis volume for the 0, 25, 100, 175 and 250 ppm NaF treatment groups, respectively. Statistically significant differences between control and NaF-treated rats were not observed with respect to absolute volume of the seminiferous tubules, interstitial space, Leydig cells, blood vessels boundary layer, lymphatic space, macrophages, tubular lumen or absolute tubular length and absolute tubular surface area, mean Sertoli cell nucleoli number per tubular cross-section, mean seminiferous tubule diameter and the mean height of the seminiferous epithelium. A statistically significant decrease in the absolute volume and volume percent of the lymphatic endothelium was observed in the 175 and 250 ppm NaF-treated groups and in the testicular capsule in the 100 ppm NaF-treated groups. The significance of this finding is unknown at the present time. Overall, the quantitative information obtained suggests that exposure to NaF at the doses used in the present study does not adversely affect testis structure or spermatogenesis in the rat.
Animals↗
Differentiated thyroid cancer: determinants of disease progression in patients <21 years of age at diagnosis: a report from the Surgical Discipline Committee of the Children's Cancer Group.
OBJECTIVE: This study was done to define the extent of disease and evaluate the effect of staging and treatment variables on progression-free survival in patients with differentiated thyroid carcinoma who were less than 21 years of age at diagnosis. SUMMARY BACKGROUND DATA: Differentiated thyroid cancer in young patients is associated with early regional lymph node involvement and distant parenchymal metastases. Despite this, the overall long-term survival rate is greater than 90%, which suggests that biologic rather than treatment factors have a greater effect on outcome. METHODS: Variables analyzed for their impact on progression-free survival in a multi-institutional cohort of 329 patients included age, antecedent thyroid irradiation, extrathyroidal tumor extension, size, nodal involvement, distant metastases, technique of thyroid surgery and lymphatic dissection, initial treatment with 131Iodine, residual cervical disease, and histopathologic subtype. Surgical complications were correlated with the specific procedures completed on the thyroid gland or cervical lymphatics. RESULTS: The overall progression-free survival rate was 67% (95%, CI: 61%-73%) at 10 years with 2 disease-related deaths. Regional lymph node and distant metastases were present in 74% and 25% of patients, respectively. Progression-free survival was less in younger patients (p = 0.009) and those with residual cervical disease after thyroid surgery (p = 0.001). Permanent hypocalcemia was more frequent after total or subtotal thyroidectomy (p = 0.001) while wound complications increased after radical neck dissections (p < 0.00001). CONCLUSIONS: The progression-free survival rate was better after a complete resection and in older patients. Progression-free survival rate was the same after lobectomy or more extensive thyroid procedures, but comparison was confounded by the increased use of total or subtotal thyroidectomy in patients with advanced disease. The risk of permanent hypocalcemia increased when total or subtotal thyroidectomy was done. Thyroid lobectomy alone may be appropriate for patients with small localized lesions while total or subtotal thyroidectomy should be considered for more extensive tumors.
Adolescent↗
Osteoblast precursor cells are found in CD34+ cells from human bone marrow.
It is known that osteoblast precursor cells are found in the low-density mononuclear (LDMN) fraction of human bone marrow (BM) aspirates. The purpose of this study was to investigate whether CD34, a hematopoietic progenitor cell marker, is present on osteoblast progenitor cells. LDMN, CD34+, and CD34- cells were cultured under conditions that promote growth and differentiation of mineral-secreting osteoblasts in a limiting dilution manner. With LDMN cells, osteoblast progenitor cells were found at an average frequency of 1/36,000 cells. With CD34- cells, osteoblast progenitor frequency remained at an average of 1/33,000, similar to LDMN cells. With CD34+ selected cells, osteoblast progenitor frequency increased to an average of 1/5,000. This osteoblast progenitor frequency is maintained in sorted CD34+/CD38+ cells. The osteoblasts generated from CD34+ cells were morphologically normal, and expression of skeletal-specific alkaline phosphatase and osteonectin increased upon differentiation induced by dexamethasone (DEX) treatment. Ultrastructurally, these CD34+ cell-derived osteoblasts displayed osteoblast-specific features. Functionally, these CD34+ cell-derived osteoblasts differentiated with DEX treatment, increased the level of cyclic adenosine monophosphate in response to parathyroid hormone stimulation, increased the level of alkaline phosphatase activity, and increased mineral secretion. These results demonstrate that osteoblast progenitor cells are enriched in the CD34+ cell population from BM and that these progenitor cells can differentiate into functional osteoblasts in culture.
ADP-ribosyl Cyclase↗
The Hickman peel-away sheath: alternative for pediatric percutaneous nephrolithotomy.
Percutaneous nephrolithotomy presents a therapeutic challenge in children because of the disproportion between the sizes of the instruments and the kidneys. A technique for pediatric nephrolithotomy used on a 2-year-old female child is presented. The patient was born prematurely and developed kidney stones as a complication of furosemide therapy. She failed medical management with hydrochlorothiazide, and the stone did not disintegrate following extracorporeal shockwave lithotripsy (ESWL). A Chiba needle was used to access the renal collecting system percutaneously. Using a guidewire, sequential dilatation was performed to 16F. A 15F Hickman catheter introduction kit was then used, and the sheath was partially peeled away. A 10F pediatric cystoscope and grasper were inserted through the sheath to remove the stones. A 12F catheter was then placed through the sheath; the sheath was peeled away, and the catheter was left indwelling for 48 hours. No complications ensued. A postoperative nephrostogram showed free drainage and absence of residual stones. Utilization of the Hickman peel-away sheath constitutes an excellent alternative nephrolithotomy technique for children with stones unresponsive to more conservative treatment.
Catheters, Indwelling↗
Coagulation factor activation in stored platelet concentrates is modulated by the platelets.
To assess alterations in coagulation proteins in stored platelet concentrates, we used a series of platelet parameters and measures of coagulation activation to compare samples collected before unit donation, during the processing of platelet concentrates (PC) from CPDA-1 blood, and in storage up to 5 days as well as stored platelet-poor plasma (PPP). Storage-dependent increases in activated partial thromboplastin time and prothrombin time were seen in both PC and PPP. However, FVII, FXI, FXII, kallikrein activity and prothrombin F1.2 levels remained unchanged in stored PC. Surprisingly, in stored PPP, significant alterations in FXII, FVII, kallikrein and prothrombin F1.2 levels were seen. Platelet morphology and surface marker studies demonstrated platelet activation during storage. These data suggest that the presence of platelets in the CLX storage container partially suppresses coagulation activation at significant cost to platelet viability.
Blood Coagulation↗
Purification of recombinant human rhinovirus 14 3C protease expressed in Escherichia coli.
A gene encoding the human rhinovirus 14 (HRV14) sequence for expression of the viral polypeptide protein delta 3ABC was inserted into a plasmid driven by the heat-inducible bacteriophage lambda PL promoter. The coding sequence was also inserted into a pET vector for expression in the T7 system to produce 13C, 15N-labeled protein. The expressed HRV14 3C protease (3Cpro) autocatalytically cleaved itself from the polyprotein delta 3ABC, and the mature HRV14 3Cpro partitioned predominantly, in the case of the T7 system, in the insoluble fraction and exclusively, in the case of the PL system, in the insoluble fraction. The insoluble HRV14 3Cpro was solubilized in urea and purified using anion- and cation-exchange chromatography. The protease was refolded/activated and further purified using a size-exclusion column. HRV14 3Cpro was purified to > 90% homogeneity as shown by SDS-PAGE and to 95% by HPLC. A continuous fluorescence assay was developed which utilized an intramolecularly quenched 9-amino-acid substrate. The substrate anthranilic acid (Anc)-Thr-Leu-Phe-Gln-Gly-Pro-Val-(p-NO2)-Phe-Lys mimicked the natural 2C/3A cleavage site (Thr-Leu-Phe-Gln-Gly-Pro-Val-Tyr-Phe) using an N-terminal anthranilic acid donor group on one side of the scissile bond (Gln/Gly) and a p-NO2-Phe acceptor group at the P4 position. Measured by the fluorescence assay, HRV14 3Cpro had a Km of 300 microM for the substrate.
3C Viral Proteases↗
Receipt of recommended medical care in HIV-infected and at-risk persons.
The authors evaluated receipt of recommended medical care for 133 HIV-infected and 101 at-risk San Francisco public health clinic patients. Fewer than half the patients received syphilis and tuberculosis screening, hepatitis B immunity testing or vaccination, and tetanus boosters. The HIV-infected persons were significantly (p < or = 0.01) more likely than the at-risk persons to receive preventive care, except for interventions specific to women. More than 80% of the HIV-infected persons received CD4 testing, zidovudine and Pneumocystis carinii pneumonia prophylaxis, and pneumococcal vaccine. Only 40% of the at-risk persons reported having HIV-antibody testing recommended. Interventions to increase care delivery to HIV-infected and at-risk persons are needed.
Adult↗
Venovenous bypass as an adjunct for the management of a retrohepatic venous injury in a child.
We report the successful utilization of venovenous bypass in the case of an 8-year-old-boy who suffered a major hepatic injury with a retrohepatic venous injury after a kick by a horse. Initial nonoperative management was successful, but a delayed hemorrhage required operation. Vascular access was obtained via the peripheral circulation, and venovenous bypass was performed without systemic heparinization. Venovenous bypass improved vascular control and allowed the repairs to be performed in a relatively bloodless field, while not compromising venous return.
Child↗
A Pit-1 binding site in the human renin gene promoter stimulates activity in pituitary, placental and juxtaglomerular cells.
One of the principal aims of our research is to determine the mechanisms which direct renin gene expression to different sites. We recently demonstrated that human renin (hRen) 5'-flanking DNA sequences -148 +/- 11 can drive the transient expression of a linked luciferase reporter gene transfected into pituitary GC cells. This activity was found to be dependent on the binding of Pit-1 to a site approximately 70 bp upstream from the transcription start site. Pit-1 is a pituitary-specific transcription factor which is involved in directing the cell-specific expression of growth hormone (GH) and prolactin (PRL) gene expression to somatotrope and lactotrope cells of the anterior pituitary. Thus, Pit-1 may be play a role in directing the expression of renin to primate lactotrope cells. Renin promoter-driven luciferase or CAT hybrid genes were found to be expressed following transfection into primary, or early passage cell cultures of placental chorionic membranes, and the renin-secreting renal tumor cell line As4.1. As with GC cells, deletion or mutagenesis of the Pit-1 site reduced activity several-fold in both placental and renal cells. These results suggest that members of the POU family of transcription factors, or some other closely related group such as the Hox proteins, participate in directing renin gene expression to placental and juxtaglomerular cells.
Binding Sites↗
Mechanism of viroid pathogenesis: differential activation of the interferon-induced, double-stranded RNA-activated, M(r) 68,000 protein kinase by viroid strains of varying pathogenicity.
Purified potato spindle tuber viroid (PSTVd) was added to an in vitro assay system containing purified interferon-induced, dsRNA-activated protein kinase (P68). Viroid RNA activated (phosphorylated) the enzyme, although with less efficiency than did the synthetic, perfectly matched poly I-poly C. In binding experiments, RNA transcripts of the intermediate strain of PSTVd were shown to specifically bind to a P68-antibody complex. Activation of the enzyme by a strain of PSTVd that results in severe symptoms in infected tomato plants was at least ten-fold that by the mild strain. Activation by a strain that results in intermediate symptoms was quantitatively similar to activation by the severe strain. To our knowledge, this is the first demonstration of a differential effect of viroid strains inducing different levels of pathology on any biochemical or metabolic system investigated. This differential effect suggests that activation of a plant enzyme homologous to mammalian P68 protein kinase may represent the triggering event in viroid pathogenesis. Differential activation of P68 is surprising, because the primary structures of the mild and severe PSTVd strains analyzed differ by only a two-nucleotide inversion (UUC-->CUU) in the lower portion of the 'pathogenicity' region of the molecules. This change, according to thermodynamic calculations, should have only a minor effect on the secondary structure of the viroid molecule. Binding assays indicated that PSTVd specifically binds to P68.
Animals↗
Diagnostic classification of patients with low back pain: report on a survey of physical therapy experts.
BACKGROUND AND PURPOSE: A survey of expert orthopedic physical therapists was conducted to assist in the development of a classification system for patients with low back pain (LBP). The goal of the survey was to measure levels of agreement on labels and accompanying constellations of signs and symptoms for subgroups of patients with LBP. SUBJECTS: Twenty-four of the 30 expert orthopedic physical therapists who were originally contacted responded to the survey request. METHODS: A modified Delphi technique was used. The first stage involved a review of the literature and identification of 25 diagnostic classes of LBP. Experts were asked to rate the "appropriateness" of each diagnostic class for inclusion in a classification scheme. Clinical findings relevant to each diagnostic class were identified and rated on the degree of "essentialness" to that class. RESULTS: Three diagnostic classes--hypomobility dysfunction, nerve root adhesion, and sacroiliac hypermobility--were distinct in that the agreement criteria for the appropriateness of diagnostic classes as well as the surveyed essential signs and symptoms were met. Six of the 25 diagnostic classes did not meet the minimum levels required for agreement as appropriate diagnostic classes: facet syndrome, chronic pain behavior, muscle strain, iliolumbar ligament sprain, posterior ligament sprain, and myofascial dysfunction. CONCLUSION AND DISCUSSION: The importance of developing homogeneous subgroups of patients with LBP based on constellations of reliable clinical findings is emphasized.
Australia↗
Change is good: one hospital's experience with optical disk.
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Hospital Bed Capacity, 100 to 299↗
Primary treatment of pelvic osteosarcoma. Report of five cases.
Five patients, ages 12 to 20 years, with nonresectable primary (Patients 2, 3, and 5) and metastatic (Patients 1 and 4) pelvic osteosarcomas were treated with intraarterial cisplatin and concurrent radiation therapy from 1983 to 1987. Long-term local tumor control was achieved in all five patients. Patients 1 and 3 are alive with no evidence of local recurrence or metastatic disease at 77 and 56 months of follow-up, respectively, since diagnosis of the pelvic tumor. Patients 2, 4, and 5 died of metastatic lung disease at 25, 39, and 12 months, respectively, after diagnosis of the pelvic tumor. Patient 4 had no clinical or radiologic evidence of local recurrence. Control of tumor growth in patients with pelvic osteosarcomas can be achieved with regional chemotherapy and concurrent radiation therapy. These patients also should receive adjuvant intensive systemic chemotherapy to increase the probability of eliminating potential subclinical metastatic disease.
Adolescent↗
Hirschsprung's disease: a possible cause of anastomotic failure following repair of intestinal atresia.
Despite several reported cases, the association of Hirschsprung's disease and intestinal atresia is not widely recognized. We describe three patients with jejunoileal atresia who all had a preoperative barium enema that failed to show a transition zone. All three patients developed an anastomotic leak of the atresia repair, and required a temporary diverting enterostomy. Two patients had total colonic Hirschsprung's disease and in one, the transition zone was in the midtransverse colon. Histological examination of the appendix at the time of repair may be helpful in patients with small intestinal atresia. In patients who develop an anastomotic breakdown, rectal biopsy should be performed to rule out Hirschsprung's disease.
Anastomosis, Surgical↗