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Biomedical subjects

T Black

Publications and source records attributed to T Black.

At least 37 records · Page 2Linked to original sources
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Synthesis of nitrogenase in mutants of the cyanobacterium Anabaena sp. strain PCC 7120 affected in heterocyst development or metabolism.

Mutants of Anabaena sp. strain PCC 7120 that are incapable of sustained growth with air as the sole source of nitrogen were generated by using Tn5-derived transposons. Nitrogenase was expressed only in mutants that showed obvious morphological signs of heterocyst differentiation. Even under rigorously anaerobic conditions, nitrogenase was not synthesized in filaments that were unable to develop heterocysts. These results suggest that competence to synthesize nitrogenase requires a process that leads to an early stage of visible heterocyst development and are consistent with the idea that synthesis of nitrogenase is under developmental control (J. Elhai and C. P. Wolk, EMBO J. 9:3379-3388, 1990). We isolated mutants in which differentiation was arrested at an intermediate stage of heterocyst formation, suggesting that differentiation proceeds in stages; those mutants, as well as mutants with aberrant heterocyst envelopes and a mutant with defective respiration, expressed active nitrogenase under anaerobic conditions only. These results support the idea that the heterocyst envelope and heterocyst respiration are required for protection of nitrogenase from inactivation by oxygen. In the presence of air, such mutants contained less nitrogenase than under anaerobic conditions, and the Fe-protein was present in a posttranslationally modified inactive form. We conclude that internal partial oxygen pressure sufficient to inactivate nitrogenase is insufficient to repress synthesis of the enzyme completely. Among mutants with an apparently intact heterocyst envelope and normal respiration, three had virtually undetectable levels of dinitrogenase reductase under all conditions employed. However, three others expressed oxygen-sensitive nitrogenase activity, suggesting that respiration and barrier to diffusion of gases may not suffice for oxygen protection of nitrogenase in these mutants; two of these mutants reduced acetylene to ethylene and ethane.

Anabaena↗
PubMed1989

Gamma-globulin enhances survival in pneumococcal-challenged asplenic infant rats.

Early augmentation of a patient's immune system can be a valuable adjunct to standard supportive and antibiotic treatment of overwhelming postsplenectomy sepsis (OPSS). Normal humoral immune factors against pneumococcal sepsis are replenished by the parenteral administration of human gamma-globulin (HGG). Monthly prophylactic administration of HGG to asplenic individuals to prevent OPSS has been suggested. The cost of such measures is prohibitive, and the risk of serum-transmitted disease is significant. We administered HGG to splenectomized infant rats with pneumococcal sepsis to determine if mortality rates could be reduced and survival time prolonged. Fifty-six three-day-old rats underwent splenectomy and another 56, laparotomy without splenectomy. Twenty-eight animals from each operative group were administered HGG and the other 28, human serum albumin (HSA), 12 and 24 hours after inoculation with varying dosages of log-phase Streptococcus pneumoniae. The LD50 for asplenic animals was less than 50 colony forming units (cfu) per animal, while for the group with spleens, the LD50 was 250 to 500 cfu. There were no significant intragroup variations in LD50 between HGG and HSA subgroups. Survival times were compared using the BMDP1L-Life Tables and Survival Functions, and the generalized Wilcoxon t-test. These data show that host immunity to pneumococcal challenge in asplenic infant animals might be fully restored by the administration of HGG, even after the onset of symptoms. Survival of an asplenic child with evidence of OPSS might be enhanced by immediate administration of HGG.

Animals↗
PubMed1988

Influenza virus regulates protein synthesis during infection by repressing autophosphorylation and activity of the cellular 68,000-Mr protein kinase.

We investigated the mechanisms by which influenza virus prevents shutoff of protein synthesis by a cellular protein kinase normally activated during infection. Earlier work has shown that influenza virus superinfection of cells previously infected by the adenovirus VAI RNA-negative mutant dl331 resulted in selective translation of influenza virus mRNAs and suppression of the elevated protein kinase levels normally found in cells infected by the mutant alone (M. G. Katze, B. M. Detjen, B. Safer, and R. M. Krug, Mol. Cell. Biol. 6:1741-1750, 1986). We elucidated the mechanisms of this kinase repression and can now report that influenza virus encodes a gene product which functions to directly block the autophosphorylation and activity of the interferon-induced, double-stranded-RNA-activated protein kinase, P68. Suppressed P68 activity was found not only in doubly infected cells but also in cells infected by influenza virus alone. Moreover, the decrease in P68 activity correlated with a decrease in the endogenous levels of phosphorylation of the alpha subunit of the eucaryotic initiation factor eIF-2, the natural substrate of the protein kinase. Suppression of P68 activity occurred as early as 2 h after influenza virus infection and required viral gene expression beyond the level of primary mRNA transcription to take place. We confirmed our in vivo observations with in vitro mixing experiments which showed that the influenza virus inhibitor can act in trans to block P68 activity. Combined repression of P68 function and eIF-2 alpha phosphorylation during influenza virus infection is essential for continued catalytic recycling of eIF-2 and efficient mRNA translation.

Animals↗