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Biomedical subjects

M Greenberg

Publications and source records attributed to M Greenberg.

At least 55 records · Page 3Linked to original sources
PubMed1999

Application of comparative genomic hybridization, spectral karyotyping, and microarray analysis in the identification of subtype-specific patterns of genomic changes in rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) in children occurs predominantly as two major histologically defined subtypes called embryonal RMS (RMS-E) and the prognostically less favorable alveolar RMS (RMS-A). Comparative genomic hybridization (CGH) was performed on 21 RMS and identified consistent gains affecting chromosomes 2 (8/10), 5 (5/10), 6 (3/10), 7 (7/10), 8 (9/10), 11 (6/ 10), and 12 (5/10) in RMS-E. Losses/deletions involved chromosomes 19 (2/10) and chromosomes 4, 9, 10, 17, 21 (1/10 each). High copy number amplification, involving the 2p24 region (5/11) and less frequently, the 12q13-21 (2/11), 9p22 (1/11), and 17q22-25 (1/11) regions, was detected in RMS-A. Gene amplification at band 2p24 was present in 6/12 alveolar tumors, and in each case, MYCN was amplified, together with the distally placed DDX1 gene. For these patients there was a shorter disease free interval and a higher mortality than patients with tumors without amplification. Detailed spectral karyotype analysis (SKY) was performed on two RMS cell lines (one of each subtype) and identified a surprisingly high level of structural change. Gene expression studies with the Atlas Human Cancer Array (588 genes) showed that 153 genes generated a signal of similar intensity in both cell lines, and 45 genes appeared to have subtype-specific expression. The chromosomal location of differentially expressed genes was compared to the pattern of genomic alteration in RMS as determined by CGH in this study and the literature.

Chromosome Aberrations↗
PubMed1999

Oncology nurses' perspectives on unconventional therapies.

Unconventional therapies have become increasingly popular with health care consumers in recent years. As patients seek information and attempt to make decisions about unconventional therapies, they often turn to nurses, asking their opinion about certain therapies. The nurse's attitudes and beliefs about unconventional therapies very likely will influence the response to the patient's inquiries. This work represents the findings of interviews with 48 nurses regarding their perspectives on unconventional therapies. Without exception, all nurses interviewed emphasized the need for information regarding unconventional therapies to be readily available for patients and health care professionals. The other themes identified in the interviews included the following: various people use unconventional therapies; people seek unconventional therapies for a variety of reasons; communication about unconventional therapies needs to be open; and conventional and unconventional practitioners ought to work collaboratively. The participants interviewed saw a clearly defined role for nurses regarding unconventional therapies.

Attitude of Health Personnel↗
PubMed1999

Nurses' perspectives on unconventional therapies.

Unconventional therapies have become increasingly popular with health care consumers in recent years. As patients seek information and attempt to make decisions about unconventional therapies, they often turn to nurses, asking the nurse's opinion about certain therapies. The nurse's attitudes and beliefs about unconventional therapies quite likely will influence the response to the patient's inquiries. This article represents the findings of interviews with 20 nurses regarding their perspectives on unconventional therapies. Without exception, all nurses who were interviewed emphasized that information regarding unconventional therapies needs to be available readily for both patients and health care professionals. Other themes identified in the interviews included the following: Various people use unconventional therapies; people seek unconventional therapies for a variety of reasons; communication about unconventional therapies needs to be open, and a place should be found for unconventional therapies. The interviewees saw a clearly defined role for nurses regarding unconventional therapies.

Attitude of Health Personnel↗
PubMed1999

Apexification & apexogenesis.

When there is pulpal involvement of permanent teeth with incompletely formed roots, techniques for the induction of apical closure should be completed before endodontic therapy is begun. Apexification is a method of inducing a calcified barrier at the apex of a nonvital tooth with incomplete root formation. Apexogenesis refers to a vital pulp therapy procedure performed to encourage physiological development and formation of the root end.

Adolescent↗
PubMed1999

Applications for guided bone regeneration in endodontic surgery.

Regeneration of apical bony defects remains a significant problem in endodontic surgery. When a resorbable membrane is placed over a defect, it acts as a barrier between the defect and the overlying gingival tissue. This barrier membrane provides sufficient time for bone to regenerate while preventing the faster growing connective tissue from invaginating into the area. When new tissue replicates the structure and function of the lost tissue, then apical regeneration has occurred.

Absorbable Implants↗
PubMed1999

Collection devices for human papillomavirus.

BACKGROUND: Human papillomavirus (HPV) testing has relied to date on samples collected by experienced health professionals. Self-administered testing devices could allow HPV testing to occur in large-scale epidemiologic studies of primary care screening populations. The purpose of this study is to determine whether a self-collection device for cervicovaginal HPV infection could be developed. METHODS: A prospective randomized trial of a consecutive sampling of 93 women, 18 years or older, receiving routine cervical cancer screening and colposcopy in the urban gynecologic clinics in Philadelphia, Pennsylvania, were randomized into 2 arms. Women in arm 1 used a self-administered tampon before the physician-directed swabs of the cervix; in arm 2, women underwent the physician-directed swab testing before using the self-administered tampon. The concordance of HPV DNA positivity between sampling methods detected by a Hybrid Capture HPV tube test for both low- and high-risk types of HPV was the main outcome measure. RESULTS: The concordance rate (ie, women whose cultures were classified as negative on both tests or positive on both tests) for arms 1 and 2 were similar: 78.3% and 80.9%, respectively. CONCLUSIONS: The tampon was equivalent to the physician-directed swab in HPV detection and suggests its feasibility in long-term primary care studies of screening populations.

Adolescent↗
PubMed1999

Achieving success with the silicone expander for overacting superior obliques.

PURPOSE: To report the results of and complications with silicone expander surgery for the overacting superior oblique. METHODS: A total of 26 patients with bilateral overaction of the superior oblique and A-pattern strabismus and 5 patients with unilateral overacting superior oblique secondary to inferior oblique palsy were treated with a 7 mm silicone expander. Care was taken not to enter the sub-Tenon's space. RESULTS: The group that underwent bilateral superior oblique surgery had an average preoperative pattern of 37.42 diopters (D) and an average correction of 35.37 D. Three patients had a severe unilateral postoperative inflammatory incident that was successfully treated with oral and topical corticosteroids. One of these patient developed Brown's syndrome. Another patient, who had no postoperative inflammatory incident, also developed Brown's syndrome. In these 4 patients, the sub-Tenon's space was inadvertently entered during surgery. CONCLUSION: The silicone expander surgery has a very high success rate in treating the A-pattern associated with the bilateral overacting superior oblique. This procedure also works well for the unilateral superior oblique that overacts owing to an inferior oblique palsy. No cyclotorsion symptoms occurred after this surgery. However, 4 patients had complications because the sub-Tenon's space was exposed during surgery. With this procedure, there is a learning curve to obtain the skill not to enter the sub-Tenon's space.

Adolescent↗
PubMed1998

A dileucine motif in HIV-1 Nef is essential for sorting into clathrin-coated pits and for downregulation of CD4.

Nef, a approximately 200 residue multifunctional regulatory protein of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), interacts with components of host cell signal transduction and clathrin-dependent protein sorting pathways. The downregulation of surface CD4 molecules and major histocompatibility complex (MHC) class I antigens by Nef is believed to be important in AIDS pathogenesis [1-7]. Nef contains a globular core domain and two disordered segments--a myristylated arm at the amino terminus and a carboxy-terminal loop projecting from the globular core [8,9]. Here, we aimed to determine the sorting signals in HIV-1 Nef that were responsible for its involvement in the clathrin-mediated pathway. We found that a sequence in the carboxy-terminal disordered loop of Nef is essential for downregulation of CD4. This sequence resembles the dileucine motif, one of two well-characterized sorting signals that target membrane proteins to clathrin-coated vesicles. The dileucine-motif-containing segment of Nef bound directly and specifically to the beta-adaptin subunit of the clathrin adaptor complexes AP-1 and AP-2, which are responsible for recruiting sorted proteins into coated pits. Unlike wild-type Nef, a mutant form of Nef that lacked the dileucine motif did not localize to clathrin-coated pits and did not downregulate CD4 expression, although it could downregulate MHC class I surface expression. Thus, the dileucine motif in HIV-1 is required for CD4 downregulation and for interaction with clathrin adaptor complexes.

Amino Acid Sequence↗
PubMed1998

Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1 alpha is mediated by the chemokine receptor CXCR4.

CXCR4, a seven transmembrane domain G-protein-coupled receptor for the Cys-X-Cys class of chemokines, is one of several chemokine receptors that can act as a co-receptor with CD4 for the human immunodeficiency virus (HIV-1) glycoprotein gp120 [1-3]. CXCR4 can mediate the entry of HIV-1 strains that specifically infect T cells, such as the IIB strain (see [4] for review). Recent reports indicate that gp120 can signal through CXCR4 [5] and it has been suggested that signal transduction, mediated by the viral envelope, might influence viral-associated cytopathicity or apoptosis [6]. Neuronal apoptosis is a feature of HIV-1 infection in the brain [7,8], although the exact mechanism is unknown. Here, we address the possible role of CXCR4 in inducing apoptosis using cells of the hNT human neuronal cell line; these cells resemble immature post-mitotic cholinergic neurons and have a number of neuronal characteristics [9-15]. We have previously shown that gp120 from the HIV-1 IIIB strain binds with high affinity to CXCR4 expressed on hNT neurons [15]. We now find that both IIIB gp120 and the Cys-X-Cys chemokine SDF-1 alpha can directly induce apoptosis in hNT neurons in the absence of CD4 and in a dose-dependent manner. To our knowledge, this is the first report of a chemokine and an HIV-1 envelope glycoprotein eliciting apoptotic responses through a chemokine receptor.

Apoptosis↗
PubMed1998

Direct and indirect estimates of HIV-1 incidence in a high-prevalence population.

While the worldwide AIDS epidemic continues to expand, directly measured incidence data are difficult to obtain. Methods to reliably estimate human immunodeficiency virus type 1 (HIV-1) incidence from more easily available data are particularly relevant in those parts of the world where prevalence is rising in heterosexually exposed populations. The authors set out to estimate HIV-1 incidence in a population of heterosexual sexually transmitted disease clinic attendees in Trinidad who had a known high prevalence of HIV-1 subtype B. Over the period 1987-1995, HIV-1 incidence estimates from serial cross-sectional studies of HIV-1 prevalence, passive follow-up of clinic recidivists, modeling of early markers of HIV-1 infection (p24 antigen screening), and a cohort study of seronegative genital ulcer disease cases were compared. Measuring incidence density in the genital ulcer disease cases directly gave the highest estimate, 6.9% per annum. Screening for the detection of early HIV-1 markers yielded an incidence of 5.0% per annum, while estimating incidence from serial cross-sectional prevalence data and clinic recidivists gave estimates of 3.5% and 4.5% per annum, respectively. These results were found to be internally consistent. Indirect estimates of incidence based on prevalence data can give accurate surrogates of true incidence. Within limitations, even crude measures of incidence are robust enough for health planning and evaluation purposes. For planning vaccine efficacy trials, consistent conservative estimates may be used to evaluate populations before targeting them for cohort studies.

Blotting, Western↗
PubMed1998

Cytological changes in endotracheal aspirates associated with chronic lung disease.

Endotracheal aspirates taken serially from mechanically ventilated premature infants born at < 28 weeks gestation between March 1992 and August 1993 were studied to determine whether early cytological changes would be a good predictor of lung damage in infants who develop chronic lung disease (CLD). CLD was diagnosed if the infant required supplemental oxygen at 36 weeks corrected gestational age. Fifty-five infants were enrolled in the study, five died and of the 50 infants remaining, 17 (34%) developed CLD. The infants with CLD had a significantly lower gestation (25.5 +/- 1.8 (mean +/- 1 SD) versus 26.2 +/- 0.9 weeks, p < 0.05), significantly more required surfactant (14/17 vs. 16/33, p < 0.05) and were ventilated for a significantly longer period (43.3 +/- 26.6 vs. 19.3 +/- 12.8 days, p < 0.0001). Endotracheal aspirate cytology showed that infants with CLD had significantly more degenerated columnar epithelial cells on day 3 (p = 0.001), and more neutrophils on day 10 (p = 0.007). Though not predictive of CLD, cytological changes consistent with bronchial epithelial and pulmonary damage followed by an inflammatory response were found in the tracheal aspirates of a group of infants clinically diagnosed with CLD.

Chronic Disease↗
PubMed1998

Identification and characterization of the CXCR4 chemokine receptor in human T cell lines: ligand binding, biological activity, and HIV-1 infectivity.

The CXCR4 chemokine receptor has been shown to respond to the C-X-C chemokine stromal-derived factor (SDF-1) and has recently been shown to be an important coreceptor for HIV-1 infection. In the present paper we have tested a number of human lymphocyte cell lines, including Jurkat, HUT78, CEM, and Sup-T1 for the presence of CXCR4 receptors. We found that these T cell lines bind SDF-1alpha and SDF-1beta with high affinity. The CXCR4 Ab 12G5 inhibited both SDF-1 binding and HIV-1LAI-mediated fusion of CEM. Scatchard analysis revealed the presence of approximately 150,000 SDF-1alpha-binding sites per cell with a Kd between 5 and 10 nM. Cross-competition experiments using unlabeled SDF-1alpha and SDF-1beta revealed that both chemokines are equally capable of displacing their radiolabeled counterparts. Internalization studies with [125]I-SDF-1alpha revealed that Jurkat cells internalized greater than 90% of the ligand by 2 h at 37 degrees C. SDF-1alpha was also chemotactic for Jurkat cells and caused an increase in the rate of extracellular acidification that was half-maximal at 18 nM SDF-1alpha and could be inhibited by pretreatment with the SDF-1 proteins, pertussis toxin, or the Ab 12G5. Finally, SDF-1alpha also caused an increase in the cytosolic Ca2+ concentration in Sup-T1 cells that was abolished by preincubating the cells with pertussis toxin or PMA and inhibited by the Ab 12G5. This molecular characterization of CXCR4 receptors should prove useful in clarifying receptor interaction with SDF-1 proteins and with HIV-1 glycoprotein, with the ultimate aim of targeting the viral interaction for therapeutic intervention.

Binding Sites↗
PubMed1998

Electronic measurement of compliance with mercaptopurine in pediatric patients with acute lymphoblastic leukemia.

UNLABELLED: Twenty-four pediatric patients with acute lymphoblastic leukemia (ALL) on maintenance therapy were evaluated for their compliance with taking their prescribed doses of oral mercaptopurine (6-MP). PROCEDURE AND RESULTS: We utilized the Medication Event Monitoring System (MEMS; Aprex Corporation, Fremont, CA) for the study. Compliance was defined as the number of days doses were taken as a percentage of the total number of days doses were prescribed during the study period. The mean age of the patients was 7.3 years (range 2.6-17.2 (years). Patients were evaluated for a mean of 44 days (range 15-94 days). Thirty-three percent of patients (8) took less than 90% and 17% (4) took less than 80% of their prescribed pills. Eight patients were also evaluated for a difference in compliance between morning and evening administration. For the comparison of compliance between a morning vs. an evening schedule a tren toward improved compliance in the evening was found. Five patients had an increase and one patient a decrease in compliance with an evening schedule (differences ranged from 0.2% to 51.3%), with two patients having 100% compliance on both schedules. CONCLUSIONS: Our data raise concern that a significant proportion of pediatric patients are non-compliant with pill taking and demonstrate that the timing of administration of 6-MP in children with ALL may be crucial in some patients and supports the hypothesis that evening administration of 6-MP is associated with a lower risk of relapse.

Adolescent↗
PubMed1998

Subsequent quality of life for children irradiated for a brain tumor before age four years.

BACKGROUND: We wanted to evaluate survival and functional morbidity following radiation treatment of brain tumors in children less than 4 years old. PROCEDURE: Outcome was evaluated for 222 children who were less than 4 years old when they were irradiated at University of Toronto Centres, 1958-1995. The status of the survivors with regard to focal neurological defects, vision, hearing, and education at last follow-up was recorded. In 23 adult survivors older than 21 years at last follow-up, information was obtained with regard to higher education, occupation, and living arrangements. RESULTS: The overall 10-year survival rate was 40%, not significantly different than the 45% for 776 4-16-year-olds with irradiated brain tumors treated at the same institutions. Forty-five percent of the survivors had no major focal neurological, visual, or hearing defects. There were no major differences in the frequencies of these criteria or of schooling between 0-2- and 2-4-year-olds. Among adult survivors, older than 21 at last follow-up, 26% successfully completed higher education, 31% were in full-time employment, and 37% had never been employed. For medulloblastoma, the 5-year survival rate was 61% for 30 children less than 3 years old and treated from 1975-1995. This compared favorably with recent reports of survival following primary chemotherapy with delayed or omitted radiation treatment. SUMMARY: Radiation treatment of a young child with a brain tumor was associated with cure in 1 of every 3 patients. Unfortunately, quality of life for many survivors was not good. Only one of every 3 adult survivors was able to have a normal life-style. This shortfall was the result of focal neurological defects which were present from the time of first treatment, and of the long-term effects of radiation treatment. CONCLUSIONS: The search for less toxic treatment remains appropriate, but is experimental and researchers must recognize that there may be a trade-off between morbidity and mortality.

Astrocytoma↗
PubMed1998

Communication of psychiatric diagnosis.

We examined whether psychiatric patients knew their diagnosis, the significance they attached to it, and the impact of being informed in a systematic fashion according to their wishes. We also assessed whether the nature of the psychiatric diagnosis influenced what patients were told by their psychiatrists. The three parts of the study included questionnaire responses from 28 consultant psychiatrists: case-note reviews and questionnaire responses of 200 adult psychiatric in-patients: and a pilot study informing 28 adult psychiatric day hospital patients of their diagnosis according to their wishes. The results showed that of 126 in-patients, 53% had not been told their diagnosis, although most wanted to know. Of those informed, 75% agreed with their diagnosis. The majority of patients considered a psychiatric diagnosis to be as real as a physical diagnosis and helpful in their treatment. Patients with schizophrenia were less likely to have been informed of their diagnosis, and psychiatrists were also more reticent regarding the diagnosis of personality disorder. All patients who were systematically informed, in the pilot study agreed with their diagnosis. We conclude that most patients agree with their diagnosis and its usefulness. All patients should be asked whether they want to know their diagnosis and be informed appropriately.

Adolescent↗