Search PubMed⌕ Search

Biomedical subjects

D M Green

Publications and source records attributed to D M Green.

At least 73 records · Page 4Linked to original sources

Transendothelial migration of lymphocytes from HIV-1-infected donors: a mechanism for extravascular dissemination of HIV-1.

To identify factors that cause HIV-1 to establish perivascular foci of infected cells, we studied the transendothelial migration of blood mononuclear leukocytes (MNL) from 76 HIV+ patients and 41 controls. The fraction of patients' lymphocytes that migrated across endothelial cell monolayers in vitro was significantly increased (p < or = 0.03) compared with that of control donors. Migration of patients' CD4+ T cells was particularly enhanced, whereas the migration of monocytes did not differ between patients and controls. Lymphocyte migration correlated with expression of CD11a/CD18 and CD49d/CD29 and with the quantity of TNF-alpha produced as MNLs migrated through the endothelium. Measurement of HIV-1 proviral DNA copies in the patients' MNLs (n = 26) suggested that in half the cases virus-infected cells accumulated preferentially amidst the migratory leukocytes. We observed the same behavior with normal donor MNLs infected, in vitro, with each of 4 strains of HIV-1. The number of HIV-1 proviral DNA copies per million MNLs was 40 to 178 times higher in the migratory population than in the original population added to the endothelium. To test whether only certain strains of HIV-1 stimulate transendothelial migration of infected cells, we used single strand conformation polymorphism analysis to identify quasispecies of HIV-1 in the MNLs. If all strains of HIV-1 were equal in their ability to stimulate transendothelial migration, we expected to find no differences in the quasispecies present in the original and migratory cell populations. In fact the quasispecies differed in 14 of 19 paired samples, suggesting that only certain HIV-1 quasispecies promote transendothelial migration of infected cells.

Acquired Immunodeficiency Syndrome↗

Complement C5a, TGF-beta 1, and MCP-1, in sequence, induce migration of monocytes into ischemic canine myocardium within the first one to five hours after reperfusion.

BACKGROUND: Recent studies suggest that reperfusion promotes healing of formerly ischemic heart tissue even when myocardial salvage is no longer possible. Since monocyte-macrophage infiltration is the hallmark of the healing infarct, we have attempted to identify mechanisms that attract monocytes into the heart after reperfusion of ischemic canine myocardium. METHODS AND RESULTS: Isolated autologous 99mTc-labeled mononuclear leukocytes injected into the left atrium localized preferentially in previously ischemic myocardium within the first hour after reperfusion. Histological studies revealed CD64+ monocytes in small venules and the perivascular connective tissue within the first hour after reperfusion. Flow cytometric analysis of cells in cardiac lymph showed systematically increasing numbers of neutrophils and monocytes between 1 and 4 hours after reperfusion; monocyte enrichment was eventually greater than neutrophil enrichment. Monocyte chemotactic activity in cardiac lymph collected in the first hour after reperfusion was wholly attributable to C5a. Transforming growth factor (TGF)-beta 1 contributed significantly to this chemotactic activity after 60 to 180 minutes, and after 180 minutes, monocyte chemotactic activity in lymph was largely dependent on monocyte chemoattractant protein (MCP)-1 acting in concert with TGF-beta 1. CONCLUSIONS: Beginning in the first 60 minutes after reperfusion, C5a, TGF-beta 1, and MCP-1, acting sequentially, promote infiltration of monocytes into formerly ischemic myocardium. These events may promote the healing of myocardial injury facilitated by reperfusion.

Animals↗

Birth defects and childhood cancer in offspring of survivors of childhood cancer.

OBJECTIVE: To determine the effect of chemotherapy for cancer during childhood and adolescence on subsequent pregnancy outcome and the occurrence of cancer in the offspring. DESIGN: We reviewed the history of 405 former patients with pediatric cancer. A self-administered questionnaire was completed by members of a cohort of consecutively treated patients who were aged 18 years or older at the most recent follow-up visit and who were at least 5 years beyond the initial diagnosis of their cancer. SETTING: Department of Pediatrics of a National Cancer Institute-designated comprehensive cancer center. RESULTS: One hundred forty-eight patients reported 280 pregnancies. Ninety-one of the patients who reported 1 or more liveborn or stillborn infants following the completion of treatment had received 1 or more chemotherapeutic agents as part of their treatment of cancer. The frequency of congenital anomalies was 3.3% among the liveborn offspring of the treated women and 3.3% among the liveborn offspring of the spouses or female companions of the treated men. No cases of childhood cancer have been diagnosed among the offspring. CONCLUSIONS: The present data suggest that prior treatment with mutagenic chemotherapeutic agents, in the dosage ranges examined, does not increase the frequency of congenital anomalies in the offspring of former pediatric and adolescent patients with cancer. Although no cases of childhood cancer have been observed thus far among the offspring, additional follow-up is necessary to adequately assess their risk of childhood cancer.

Abnormalities, Drug-Induced↗

SIOP Working Committee on psychosocial issues in pediatric oncology: guidelines for communication of the diagnosis.

This is the fourth official document of the SIOP Working Committee on psychosocial issues in pediatric oncology constituted in 1991. This document develops another topic discussed and approved by the SIOP Committee: "communication of the diagnosis" is addressed to the pediatric oncology community as guidelines that could be followed. The highly stressful nature of the diagnostic period must be acknowledged, and communication involving the staff and all family members should cover both medical and psychosocial issues. A well-planned and extensive initial session should be followed by continuing discussions. The goal is a knowledgeable family that can talk openly with its members and with the staff.

Adolescent↗

Wilms' tumor.

Wilms' tumor is the most common renal malignancy of childhood. Survival rates for favorable histology of Wilms' tumor currently approach 90%. Recent advances in the molecular genetics of Wilms' tumor have led to insights into the genetic factors involved in the development of Wilms' tumor, normal renal development, and the mechanisms of tumorigenesis.

Combined Modality Therapy↗

Platelet gel: an autologous alternative to fibrin glue with applications in oral and maxillofacial surgery.

The preparation and use of platelet gel, an autologous formulation of fibrin glue, are described. The unique features of this biologic sealant are that it is derived from autologous blood collected in the immediate preoperative period by the anesthesiologist, it contains a high concentration of platelets, and it can be used in patients who are not candidates for blood bank donation. Platelet gel has been used successfully in the area of reconstructive oral and maxillofacial surgery in conjunction with ablative surgery of the maxillofacial region, mandibular reconstruction, surgical repair of alveolar clefts and associated oral-antral/ oral-nasal fistulas, and adjunctive procedures related to the placement of osseointegrated implants.

Blood↗

Percutaneous penetration of N-nitroso-N-methyldodecylamine through human skin in vitro: application from cosmetic vehicles.

The human skin penetration of N-nitroso-N-methyldodecylamine (NDOMA) from isopropyl myristate (IPM) and two vehicles representative of cosmetic/personal care formulations was determined in vitro. When applied as an infinite dose in IPM (1 microgram/microliter) the average total absorption over 48 hr was 0.10 +/- 0.01% of the applied dose (all data are expressed as means +/- SE). When applied as a finite dose in a representative oil-in-water emulsion formulation the average total absorption over 48 hr was 4.66 +/- 0.76% of the applied dose. When applied as a finite dose in a representative shampoo formulation for 10 min, followed by rinsing (to represent in-use exposure conditions), the average total absorption over 48 hr was 0.75 +/- 0.17% of the applied dose. Approximately 72% of the NDOMA in the applied shampoo formulation was removed by rinsing. The overall data indicated that NDOMA could penetrate the skin but that penetration was low. The rate and extent of absorption, however, could be affected by differences in the vehicle of application, time of exposure and whether the formulation is (and the conditions are designed to mimic) a rinse-off or leave-on product.

Carcinogens↗

Wilms' tumour.

Explore the source record for details and available documents.

Antineoplastic Agents↗

Evaluation of maximum-likelihood estimators in nonintensive auditory psychophysics.

This is a brief report on the use of maximum-likelihood (ML) estimators in auditory psychophysics. Slope parameters of psychometric functions are characterized for three nonintensive auditory tasks: forced-choice discrimination of interaural time differences (delta ITD), frequency (delta f), and duration (delta t). Using these slope estimates, the ML method is implemented and threshold estimates are obtained for the three tasks and compared with previously published data. delta ITD thresholds were additionally measured for human observers by means of two other psychophysical procedures: the constant-stimuli (CS) and the 2-down 1-up methods (Wetherill & Levitt, 1965). Standard errors were smallest for the ML method. Finally, simulations showed ML estimates to be more efficient than the CS and k-down 1-up procedures for k = 2 to 5. For up-down procedures, efficiency was highest for k values of 3 and 4. The entropy (Shannon, 1949) of ML estimates was the smallest of the simulated procedures, but poorer than ideal by 0.5 bits.

Auditory Perception↗

Renal failure in Wilms' tumor patients: a report from the National Wilms' Tumor Study Group.

This report defines the incidence and determines the etiology of renal failure (RF) in patients undergoing treatment for Wilms' tumor (WT). The database of the National Wilms' Tumor Study (NWTS) was searched to identify all children reported to have developed chronic renal failure. There were 55 patients found to have RF. Of these, 39 patients had bilateral tumors, 15 with unilateral disease and one with a WT in a solitary kidney. The median interval from diagnosis to the onset of renal failure was 21 months. The incidence of RF in bilateral WT was 16.4% for NWTS-1 & -2, 9.9% for NWTS-3, and 3.8% for NWTS-4. The incidence of RF in unilateral WT remained stable. The most common etiologies of RF were: bilateral nephrectomy for persistent or recurrent tumor (24 pts), Drash syndrome (12 pts), progressive tumor in the remaining kidney (5 pts), radiation nephritis (6 pts), and other causes (5 pts). The etiology of renal failure was not reported in three children. Children with unilateral WT and a normal contralateral kidney have a very low incidence of RF, and this review does not support a recommendation for parenchymal sparing procedures in these patients. Children with bilateral WT are at risk for the development of RF, and parenchymal sparing procedures are warranted.

Child↗

Treatment of children with stage IV favorable histology Wilms tumor: a report from the National Wilms Tumor Study Group.

The purpose of this study was to evaluate the effect of the sequential addition of doxorubicin and cyclophosphamide to the combination of vincristine and actinomycin D on the relapse-free survival of children with stage IV/favorable histology Wilms tumor. We reviewed the clinical courses of all randomized patients from National Wilms Tumor Study (NWTS)-2 and 3 with stage IV/favorable histology (FH) Wilms tumor. We determined the four-year relapse-free survival percentage for patients treated on NWTS-2 with the combination of vincristine (VCR) and actinomycin D (AMD) with (regimen D) or without (regimen C) doxorubicin (DOX), and for patients treated on NWTS-3 with the combination of VCR+AMD+DOX with (regimen J) or without (regimen DD-RT) cyclophosphamide (CTX). All children received whole lung radiation therapy. The four-year relapse-free survival percentage for children with stage IV/FH Wilms tumor treated with regimen C was 53.3%, compared to 57.7% for those treated with regimen D (P = 0.63). The four-year relapse-free survival percentage for children with stage IV/FH Wilms tumor treated with regimen DD-RT was 79.0%, compared to 80.9% for those treated on regimen J (P = 0.79). The four-year relapse-free survival for children with lung metastases only treated with regimen D on NWTS-2 was significantly lower than that of children treated with the related regimen DD-RT on NWTS-3 (P = 0.03). We conclude that the addition of doxorubicin to the combination of vincristine and actinomycin D and pulmonary irradiation did not clearly improve the four-year relapse-free survival percentage of children with stage IV/FH Wilms tumor, although the benefit may have been masked by the greater frequency of death due to toxicity in NWTS-2. There was no evidence that the addition of CTX to the three-drug treatment regimen improved the four-year relapse-free survival percentage of children with stage IV/FH Wilms tumor. The data with only two drugs derived from NWTS-2 suggest that there is a population of children with stage IV/FH Wilms tumor who can be successfully treated without an anthracycline. The goal of future research will be to identify this subgroup at the time of initial diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment of endodermal sinus tumor in children using a regimen that lacks bleomycin.

BACKGROUND: The EPO-VAC protocol was initiated to study 1) the efficacy of adding a cisplatin regimen (EPO) to VAC alone (the previous standard of care) and 2) the effect of replacing bleomycin with etoposide in the treatment of pediatric endodermal sinus tumors. METHODS: The eligibility requirements for entry included age <21 years at diagnosis, diagnosis of a primary gonadal or extragonadal tumor (excluding central nervous system tumors and stage I testicular tumors), and histological confirmation of endodermal sinus tumor. Children who met the eligibility criteria were treated with four courses of EPO (etoposide, cisplatin, vincristine) alternating with three courses of VAC (vincristine, dactinomycin, and cyclophosphamide). RESULTS: Eleven children were entered on the protocol. Six patients had extragonadal disease, five patients had ovarian primaries. Seven patients had low-stage tumor (I or II) and four had advanced-stage tumor (III or IV). Three of six evaluable patients attained a complete response at 21 weeks. Three patients with a residual soft tissue mass at restaging underwent further therapy. No patient has relapsed after a median of 51 (range 14-88) months of follow-up. CONCLUSIONS: The results of this protocol suggests that a cisplatin-containing regimen that lacks bleomycin is active in childhood endodermal sinus tumors.

Adolescent↗