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M Greenberg

Publications and source records attributed to M Greenberg.

At least 19 recordsLinked to original sources
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

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↗
PubMed1998

Lack of cisplatin-ranitidine kinetic interactions: in vivo study in children, and in vitro study using dog renal brush border membrane vesicles.

The interactions between cisplatin and organic ions have been extensively investigated in animal models for the potential to reduce cisplatin cellular uptake and resultant nephrotoxicity. To further investigate the beneficial interaction clinically, we studied the effects of the organic cation, ranitidine, on the renal handling of cisplatin in children. In parallel, we examined the effects of cisplatin on the uptake kinetics of organic cations and anions by brush border membrane vesicles (BBMV) prepared from dog renal cortex. The results indicate that: 1) there is no measurable effect of ranitidine on renal clearance of cisplatin in children; and 2) BBMV uptake of anionic p-aminohippurate, but not cationic N-methylnicotinamide, is inhibited by cisplatin at concentrations of <1 mM. These findings suggest that cisplatin may not share transport systems with organic cations to a clinically significant degree. Assuming that renal tubular transport is a prerequisite for cisplatin nephrotoxicity, the lack of apparent kinetic interactions between cisplatin and organic cations may preclude clinical use of organic cations as a modality to prevent cisplatin nephrotoxicity.

Adolescent↗
PubMed1998

The information needs of well, longer-term survivors of breast cancer.

Nine focus groups for well, longer-term survivors of breast cancer were held in Ontario, Canada. Prevalent themes identified through analysis of focus group transcripts fell into two broad categories, one reflecting the context within which women seek information and the other reflecting the content of information desired and sought. Themes related to context included: the ongoing impact on women of their initial disease experience and continued uncertainty about possible recurrence; womens' lack of information and understanding about processes involved in developing medical knowledge; prevailing mistrust about the impact of cost curtailment policies; and, concerns related to how professional communication can aid or hinder the goal of obtaining information. Themes related to content issues included: follow-up protocols, tamoxifen, detecting signs of possible recurrence, prevention for daughters, neglected side effects of treatment, insurance, lifestyle, and unconventional therapies.

Adult↗
PubMed1998

A strategy for informing patients and health professionals about unconventional cancer therapies.

BACKGROUND: A Guide to Unconventional Cancer Therapies was produced by the Ontario Breast Cancer Information Exchange Project with the intention of meeting needs of patients, family members, and health professionals for information about unconventional therapies. Concerns raised by health professionals during the development of the guide serve as a focus for considering its impact on cancer patients who purchased it. MATERIALS AND METHODS: Purchasers of the guide were sent a survey questionnaire inquiring about their access to, use of, and attitudes toward it. RESULTS: A total of 634 individuals responded to the survey, including cancer patients, health professionals, and family members. The guide was rated moderately helpful overall, and health professionals found it significantly more helpful than did cancer patients. A minority of patients were influenced to try an unconventional therapy as a result of reading the guide. Those who did try a new therapy typically chose ones that are most popular and have few potential negative effects. CONCLUSIONS: As an informational strategy, the Guide to Unconventional Cancer Therapies has been successful. Concerns expressed by some health professionals about potential harm through implementing the strategy have been shown to be largely unwarranted, at least for study respondents.

Breast Neoplasms↗
PubMed1998

A survey of New Jersey industrial hygienists and safety engineers: health and safety conditions, practices, and priorities for OSHA reform.

This study reports the results of an analysis of responses from more than 400 New Jersey industrial hygienists and safety engineers to a survey examining a wide range of health and safety conditions and practices. Findings are reported on a number of variables including the types and seriousness of safety and health hazards encountered at the respondents' work sites, perceived improvements in health and safety conditions, compliance with right-to-know requirements, the effectiveness of resources used in correcting hazards, and the barriers encountered in addressing hazardous conditions. The respondents were also asked to rank their priorities regarding 14 proposals for Occupational Safety and Health Administration (OSHA) reform. Opinion questions were scaled to reflect the respondent's sense of the importance of each variable. One finding of particular interest is that worker involvement in health and safety committees was perceived as an "effective" or "very effective" resource by more than one-half of the respondents. Changes in the Occupational Safety and Health Act that would strengthen requirements for worker participation were among the respondents' top priorities for OSHA reform.

Attitude of Health Personnel↗
PubMed1998

Outcome analysis of rhabdomyosarcoma of the lower urinary tract.

PURPOSE: Multimodal therapy has resulted in a high cure rate for genitourinary rhabdomyosarcoma. We propose that the strategy of induction chemotherapy followed by excision and reconstruction without radiotherapy may provide a high cure rate without the late sequelae of pelvic radiotherapy. MATERIALS AND METHODS: We reviewed the records of 13 patients with a mean age of 3.3 years diagnosed with rhabdomyosarcoma of the urinary tract from 1986 to 1996. The primary site was the bladder in 4 cases and prostate in 9. After biopsy confirmation of the diagnosis patients were treated with chemotherapy and subsequent surgery, while radiotherapy was reserved for those with residual disease. RESULTS: After induction chemotherapy 8 patients underwent tumor excision via an organ sparing approach, which involved radical prostatectomy and partial cystectomy with or without bladder augmentation. In 5 patients the final pathological analysis showed positive margins. Repeat surgery in 6 patients included complete cystectomy and urinary diversion in 2 who had positive margins and recurrence after radiotherapy, urethrectomy and continent diversion for positive margins in 1, partial cystectomy and continent diversion in 1, and radical prostatectomy, partial cystectomy and continent diversion in 1 with stage IV disease who had local recurrence. In the latter case ileocystoplasty had been performed for a small noncompliant bladder. Six patients with microscopic residual or metastatic disease received radiotherapy. At a mean followup of 5.6 years 11 patients are disease-free. Continence was preserved in all reconstructed cases. Erections were reported in 8 patients, and renal function was maintained in 10. CONCLUSIONS: Our results suggest that urinary tract reconstruction may be safely performed at primary excision surgery, radiotherapy induced morbidity may be minimized by limiting radiotherapy to residual and metastatic disease, frozen section results may be false-negative, potency may be achieved and radiological disappearance of the tumor should be confirmed histologically.

Child↗
PubMed1998

Information needs of women with metastatic breast cancer.

Eight focus groups involving women with metastatic breast cancer were held across Ontario over approximately 6 months in 1996-97. Prevalent themes identified during the sessions are reported under 2 broad dimensions: the women's expressed desire for information in specific content areas, and issues related to whether information can be either beneficial or harmful, depending on how it is provided. The women reported high needs for information, especially that which would relate to their situation. Perceived adequacy of information is closely linked to health professional engagement and care. Although the provision of information is important, the needs of these women for maintenance of hope and provision of interpersonal support and comfort are also critical.

Adult↗
PubMed1997

Autonomic response to change of posture among normal and mild-hypertensive adults: investigation by time-dependent spectral analysis.

In this study, we applied the time-dependent spectral analysis approach (SDA) to investigate the autonomic changes occurring during a transition from supine to standing position (CP), in normal and unmedicated mild hypertensive subjects. The SDA method enables an accurate follow-up of the instantaneous changes in autonomic activity, even during the unsteady phase of the transition, where sudden changes in heart rate (HR) and arterial blood pressure (ABP) are observed. We were able to quantify the vagal withdrawal (reflected in the high frequency component of the time-dependent spectrum of HR fluctuations) in the immediate response to CP and the more slowly following sympathetic increase (reflected in the low frequency component of ABP). This general pattern was observed in both groups. In addition, our results identified an altered sympathetic response to CP in mild-hypertensives, as compared to normal adults. Their basal sympathetic activity is enhanced (higher mean HR and increased low frequency fluctuations in ABP) and their response to CP is reduced, as reflected only in the LF content of ABP fluctuations, relative to normals. No difference was observed in HR fluctuations, showing that there is no parasympathetically mediated alteration of the baroreflex control of HR in mild-hypertension.

Adult↗
PubMed1997

Cervical specimens collected in liquid buffer are suitable for both cytologic screening and ancillary human papillomavirus testing.

BACKGROUND: Several new techniques have been developed to improve the sensitivity of cervical carcinoma screening and reduce equivocal cytologic diagnoses referred to as atypical squamous cells of undetermined significance (ASCUS). This study evaluates the effectiveness of combining two newly introduced diagnostic techniques: preparation of thin-layer cytologic slides from ThinPrep liquid buffer and selected Hybrid Capture testing for human papillomavirus (HPV) DNA. Because HPV DNA detection has been strongly associated with the presence of a cervical carcinoma precursor ("squamous intraepithelial lesion," or SIL), HPV testing might be useful for identifying women with ASCUS who have an underlying SIL. METHODS: Two hundred specimens demonstrating diverse cervical abnormalities were selected from a prospective population-based study of 9174 women conducted in Costa Rica. The entire cohort had been screened with conventional cervical smears; ThinPrep slides made from liquid buffer, PAPNET, a computerized slide reading system; and Cervicography. Patients with any abnormal screening test were referred for colposcopy, punch biopsy, and loop excision of cases with high grade cytologic abnormalities not explained by punch biopsy. For this investigation, the results of ThinPrep cytology and HPV testing alone and in combination were compared with the final diagnoses, with an emphasis on the detection of carcinoma and high grade SIL. RESULTS: The 200 subjects studied included 7 women with a final diagnosis of carcinoma, 44 with high grade SIL, 34 with low grade SIL, 51 with a variety of equivocal diagnoses, and 64 with normal diagnoses. A ThinPrep cytologic diagnosis of SIL or carcinoma was made in 39 (76%) of the 51 women with final diagnoses of high grade SIL or carcinoma. Hybrid Capture testing detected carcinoma-associated types of HPV DNA in 100% of women with carcinoma, 75% with high grade SIL, 62% with low grade SIL, 20% with equivocal final diagnoses, and 12% of normal women. If colposcopy referral had been limited to women with a ThinPrep diagnosis of SIL or a diagnosis of ASCUS associated with the detection of carcinoma-associated HPV DNA from the same vial, 100% of women with carcinoma and 80% with high grade SIL would have been examined. To achieve this high sensitivity in the entire population of 9174 women would have required the referral of about 7% of the population. The combined screening strategy would have performed marginally better than optimized conventional screening with referral of any abnormal cytology (ASCUS and above). CONCLUSIONS: A cervical carcinoma screening technique which uses a single sample for cytopathology and HPV testing to triage equivocal diagnoses may be promising if it proves to be cost-effective.

Carcinoma↗
PubMed1997

A battle for compensation for Welsh coal miners: JS Haldane v "Sericite" Jones, 1932-1934.

Toward the end of the 1920s, technical advances in mining led to an increase in airborne burdens of dust in the South Wales coal mines. This coincided with a dramatic increase in the incidence of disability and death from respiratory disease among the miners. For their condition to be compensable, claimants were required to have worked with rock containing more than 50% 'free silica.' Dr W.R. Jones, a mining geologist, was asked to help obtain compensation for those claimants who could not satisfy the 'free silica' condition. He was unable to identify high-silica rocks where none had been said to exist. He did however, successfully argue the brief against the eminent Professor J.S. Haldane (who was the dominant authority, having had lengthy experience in the field of health and mining), for the fibrous form of sericite being commonly the important agent responsible for pneumoconiosis. As a consequence, the category of miner eligible for compensation was broadened. Evidence was gathered worldwide that supported the hypothesis that silicates and not just crystalline silica could cause pneumoconiosis. Despite the suspicions raised about the special power of mineral fibers during this public debate, some 40 years were to elapse before potential health hazards from fibers other than asbestos were to be taken seriously and investigated.

Coal↗
PubMed1997

Professor Matthew Stewart: asbestosis research 1929-1934.

Matthew Stewart, Professor of Pathology at Leeds University, developed an interest in asbestosis during the late 1920s. In 1929, the Medical Research Council (MRC), encouraged by an advisory committee, funded research into asbestosis at Leeds University. Stewart supported by physicians designed a program of clinical, radiological and physiological studies to follow up Merewether's affected asbestos workers. Unfortunately, this met with opposition from industry, and the Home Office Factory Department was reluctant to assist, so it was abandoned. Industry did, however, cooperate with Stewart's studies on the effects of exposing guinea pigs in the factory environment, but this led to little in the way of publication. The failure of the Leeds School to realize its potential in investigating the effects of asbestos in humans, results in part from the discouragement it received and in part from the limited time and energies available to persons with a wide range of active interests. Some 45 years were to elapse before the MRC were enabled to carry out an analysis of the clinical, radiological and physiological data of a population of asbestos workers.

Asbestosis↗