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Biomedical subjects

D Goldberg

Publications and source records attributed to D Goldberg.

At least 145 records · Page 8Linked to original sources
PubMed1995

G/C element contributes to the cell line-specific expression of the proximal osteocalcin promoter.

Sequential activation of cell type-specific genes occurs during osteoblast development. The promoter of one such gene, osteocalcin, has been widely studied, but the DNA sequences that govern osteoblast-specific expression have not been defined. The proximal osteocalcin promoter linked to pTKCAT directs strong promoter activity in osteoblast-like ROS17/2.8 cells and comparatively weak promoter activity in nonosteoblastic NIH3T3 cells. To identify sequences important in conferring cell-specific expression of the osteocalcin gene, a deletion series of the human proximal promoter was constructed and the activities assessed in ROS17/2.8 and NIH3T3 cells. These studies identified a 30 bp sequence within the proximal promoter (osteocalcin repressor element-1 [ORE-1]) which is responsible for repressing the transcriptional activity in NIH3T3 cells. In electrophoretic mobility shift assays from both NIH3T3 and ROS17/2.8 cells, a protein complex bound to the ORE-1 that was related to a complex which binds the G/C-rich repressor element in the collagen type I (alpha 1) promoter. In addition, there was a second complex from NIH3T3 cells but not ROS17/2.8 cells that bound the ORE-1 fragment. The presence of this additional factor in NIH3T3 cells parallels the observation that constructs carrying the ORE-1 sequence have repressed promoter activity relative to the analogous constructs lacking the ORE-1 when transfected into NIH3T3 and suggests that the NIH3T3-specific factor is a repressor. These data indicate that the G/C element in the ORE-1 contributes to the repression of osteocalcin gene transcription in a nonosteoblast cell line. The high homology between the ORE-1 sequence and a related sequence in the collagen type I (alpha 2) proximal promoter suggests that homologous regions in other osteoblast-expressed genes may function similarly.

3T3 Cells↗
PubMed1995

The preparedness to share injecting equipment: an analysis using vignettes.

This paper reports on the use of vignettes to study drug injectors' preparedness to share injecting equipment. Separate vignettes referring to borrowing and passing on injecting equipment have been submitted to 505 injecting drug users in Glasgow. Injectors were asked to identify their own likely response in each of the situations described within the vignettes. It was shown that even among those injectors not reporting any actual sharing in the last 6 months a significant proportion would still be prepared to share injecting equipment within certain situations. The preparedness to share injecting equipment was seen to be influenced by such factors as social distance, sex and length of time injecting. It is suggested that even in situations where drug injectors may have modified their behaviour in the direction of lower levels of reported sharing, a propensity to share may remain. This suggests the continuing need to provide injectors with easy access to sterile injecting equipment; in addition, services working with injecting drug users may need to focus not only upon actual sharing behaviour but also upon what we have described here as the preparedness to share. Indeed, the latter dimension should stand as a warning to services of the potential for sharing injecting equipment to increase in the future.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The osteocalcin and collagen type I (alpha 1) promoters share common basal regulatory units.

Sequential activation of osteoblast-specific genes occurs during cell development. Regulation of these genes is through the cooperation between basal, hormone-responsive, and growth factor-responsive transcriptional control elements. The active hormone, 1,25-dihydroxyvitamin D3 plays an important role in the regulation of osteocalcin and other osteoblast-expressed genes. As well as containing a vitamin D response element, the upstream region of the osteocalcin promoter also has potent basal activity in the osteoblast-like ROS17/2.8 cell line. The present study identifies a short DNA sequence that contributes to basal promoter activity. This osteocalcin cis-acting response element (OSCARE-1) has two basal regulatory elements: a G/C-rich element and an adjacent reverse CCAAT element. Homologous sequences have been characterized as negative and positive basal regulatory elements, respectively, in the promoter of the collagen type I (alpha 1) gene. In electrophoretic mobility-shift assays, this collagen regulatory unit and OSCARE-1 produce similar banding patterns and bind common ROS17/2.8 nuclear proteins. Mutations of the G/C element in the collagen promoter showed that it functions as an inhibitory element in NIH-3T3 cells. Introduction of the same mutations into the G/C element of the OSCARE-1 unit exposed a similar repressive activity in NIH-3T3 cells, which correlated with an altered electrophoretic mobility-shift assay banding pattern. We have shown a similarity between a basal regulatory unit in the distal osteocalcin promoter and a unit in the proximal collagen type I (alpha 1) promoter. The fact that similar units are present in other osteoblast-specific promoters suggests that OSCARE-1-like units may be a common regulator of osteoblast-expressed genes.

3T3 Cells↗
PubMed1995

The field trial of the mental disorders section of ICD-10 designed for primary care (ICD10-PHC) in England.

This study reports the English field trial of a primary health care version of the section of ICD-10 dealing with mental disorders. The classification gives guidance on both diagnosis and management of 24 common disorders. Fifty doctors collaborated with the study, in four different locations, and 40 completed all their assessments. The new classification has been well received, and there was an increase in the participants' interest in mental disorders and in their confidence in making diagnoses. Use of the depression card increased the range of symptoms considered when making a diagnosis of depression, increased the threshold for prescription of antidepressants, and added to the management suggested for depressive illnesses. The many constructive comments made about the cards will be taken into account by WHO when the classification is revised later in 1995.

Adult↗
PubMed1995

HIV/AIDS-related behavior change among injecting drug users in different national settings.

OBJECTIVES: To identify factors associated with effective AIDS behavior change among injecting drug users (IDU) in different national settings. DESIGN: Cross-sectional surveys of IDU, with determination of HIV status. Trends in city HIV seroprevalence among IDU also used to validate effectiveness of behavior change. SETTING AND PARTICIPANTS: Subjects recruited from drug-use treatment programs and outreach efforts in Bangkok, Thailand (n = 601), Glasgow, Scotland (n = 919), New York City, USA (n = 2539), and Rio de Janeiro, Brazil (n = 466). RESULTS: Evidence for the effectiveness of self-reported risk reduction was available for all cities. Univariate followed by multiple logistic regression analyses were used to identify factors associated with self-reported AIDS behavior change. Separate analyses were conducted for each city. Talking about AIDS with drug-using friends was significantly associated with behavior change in all four cities. Talking with sex partners about AIDS, educational level, knowing that someone can be HIV-infected and still look healthy, and having been tested previously for HIV were each significantly associated with behavior change in three of the four cities. CONCLUSIONS: Despite the substantial differences in these national settings, there were common factors associated with effective risk reduction. In particular, risk reduction appears to occur through social processes rather than through individual attitude change. HIV prevention programs need to explicitly incorporate social processes into their work.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Cost-effectiveness studies in the evaluation of mental health services in the community: current knowledge and unsolved problems.

Care in the community has consistently been found to be cheaper, and has often been found to be better, for selected patients on demonstration sites. Most cost advantages are obtained by shortening or even eliminating the initial period of in-patient care. Health economists can compute cost equations which relate clinical characteristics of patients to treatment costs incurred later. As old long stay patients are discharged, a degree of cost inflation is inevitable for both the hospital and the community service. Strong links have been shown both between costs and client needs, and costs, and client outcomes. Integrating mental health services with primary care has been shown to increase total costs of the service, but to decrease costs per treated case. One weakness of CMH schemes is that they are vulnerable to sudden cutbacks, so that the shift of resource to the community may not actually occur. The evidence about the efficacy of case management is conflicting, but day-care can be used as a method of shortening initial admission for some patients.

Community Mental Health Services↗
PubMed1995

Affective and neurotic disorders in community-based services: a comparative study in south Verona and south Manchester.

The service utilization by patients with affective and neurotic disorders in two defined populations of south Verona in Italy and south Manchester in England was compared. The composition and function of the two community-based psychiatric services, and the sociodemographic characteristics of the two centers are described and related to epidemiologically based data on service use in the community, outpatient clinic, day hospital and inpatient care. The results suggest that close liaison with primary care in south Manchester results in more referrals, and therefore higher treated incidence and prevalence rates. The close integration between hospital and community staff in south Verona is associated with greater permeability of the filter between inpatient and community care, indicated by higher admission rates for patients known to the service, and shorter length of inpatient stay (only for affective disorders) in south Verona compared with south Manchester.

Adolescent↗
PubMed1995

A comparison of community-based care for schizophrenia in south Verona and south Manchester.

BACKGROUND: The community-oriented mental illness services providing care to defined populations in south Verona, Italy (17,628 adults) and south Manchester, England (12,021 adults) have been compared to explore relationships between service organisation and patterns of service use. METHOD: The composition and function of the two services and the sociodemographic characteristics of the two centres are described and related to epidemiological data on service use in the community, out-patient clinic, day hospital and in-patient care. RESULTS: Treated incidence of all psychiatric diagnoses and of schizophrenia were significantly higher in south Manchester than south Verona, indicating that the referral filter between primary and secondary care is more permeable in Manchester. Patients known to the service were more likely to be admitted and to have shorter in-patient stays in south Verona, indicating that the filter between in-patient care and the community is more permeable in Verona than Manchester. CONCLUSIONS: The organisation of services in Verona results in a smaller load on the mental health service; the shorter hospital stays can be related to better integration between hospital and community resources. The organisation of services in Manchester provides care for a greater proportion of the population, but would be likely to require increased resources for the mental health services over time.

Adolescent↗
PubMed1995

New classification for mental disorders with management guidelines for use in primary care: ICD-10 PHC chapter five.

A primary care version of the International classification of diseases (10th revision) chapter five for mental and behavioural disorders (ICD-10 PHC chapter five) has been developed. This provisional version focuses on 24 conditions which are frequently seen in primary care and which can be managed effectively by general practitioners. The classification is accompanied by a flipcard for each of the conditions. The cards have diagnostic guidelines on one side and management guidelines on the other. The latter provide information which should be given to the patient, advice on the content of counselling, the available treatment methods, and indications for specialist referral. This classification system is also supported by diagnostic decision making aids, medication cards, and patient leaflets to facilitate the recognition and management of patients with mental disorders in primary care settings. The draft version of ICD-10 PHC chapter five will be finalized after field trials which will test the applicability and usefulness of the system in different primary care settings in various countries.

Depression↗
PubMed1995

A new form of primary, localized, corneal amyloidosis: a case report with confocal microscopy.

We present a case of bilateral, primary, localized, corneal amyloid deposition with a unique appearance not, to our knowledge, previously described. The patient was a 73-year-old white man who complained of glare. Best corrected visual acuity was 20/25 in both eyes. Slit lamp examination revealed subepithelial/anterior stromal white-gray deposits in the peripheral cornea in both eyes. The corneal surface was smooth with no elevated areas. Superficial corneal scrapings showed focal deposits of an amorphous, glass-like material below the epithelial surface and within Bowman's membrane, which stained with Congo red. We examined the amyloid deposits using the confocal microscope to obtain high magnification images in vivo. The confocal microscopic views showed intercellular, cotton candy-like, fibrillar amyloid material scattered throughout the anterior stroma. The use of this instrument may permit clinical diagnosis of this rare disorder without the need for biopsy.

Aged↗
PubMed1994

Cdc25 is not the signal receiver for glucose induced cAMP response in S. cerevisiae.

The Ras/cAMP pathway in the yeast S. cerevisiae couples the cell cycle of this unicellular organism to the availability of nutrients. Glucose derepressed S. cerevisiae cells respond to glucose addition by an intracellular rise in cAMP. In the prevailing model, yeast Ras plays a similar role to that of heterotrimeric G-proteins coupled to cell surface receptors. A crucial element of this model is that the exchanger, Cdc25 is activated by glucose. Such activation would result in a glucose-dependent rise in GTP-bound Ras concentration. We here show, in contrast to this view, that Cdc25 cannot be the receiver of the glucose signal. We suggest that the Ras-GTP/cyclase complex is the molecular element directly receiving the signal while Cdc25-dependent exchange constitutes a prerequisite for complex formation.

Adenylyl Cyclases↗
PubMed1994

A new classification for mental disorders with management guidelines for use in primary care: the ICD-10 PHC.

A Primary Care Version of International Classification of Diseases (10th Revision) Chapter V. for Mental and Behavioural Disorders (ICD-10 PHC) has been developed. This version focuses on 24 conditions which are frequently seen in primary care and which can be managed effectively by general practitioners. The classification is accompanied by flipcards one for each of the conditions. The cards contain diagnostic guidelines on one side and management guidelines on the other. The latter provide information which should be given to the patient, advice on the content of counselling, the available treatment methods, and indications for specialist referral. This classification system is also supported by diagnostic decision making aids, medication cards, and patient leaflets to facilitate the recognition and management of patients in primary care settings. The draft ICD-10 PHC will be finalized after the field trials which will test the applicability and usefulness of the system in different primary care settings in various countries.

Humans↗
PubMed1994

Transcriptional activation of the human osteocalcin gene by basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) has been detected in bone cells and stimulates osteoblast proliferation; however, its role in the regulation of bone metabolism remains speculative. We demonstrated that the human osteocalcin promoter is activated by bFGF when transfected into rat osteoblastic (ROS 17/2.8) cells. This effect is concentration dependent, with a twofold induction at 10 ng/ml detected after 20 h. The bFGF response is independent of both the 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and retinoic acid activation of the osteocalcin promoter. To identify the promoter sequences through which bFGF exerts its effect, we tested a series of promoter deletion constructs for their response to bFGF. Deletion of the upstream region between -673 and -588 bp results in a significant loss of induction. Gel-shift analysis demonstrates that proteins present in ROS 17/2.8 nuclear extracts bind specifically to these sequences. This region alone was unable to confer the bFGF response on a minimal osteocalcin or an heterologous promoter. However, sequences between -678 and -476 bp, which also includes the vitamin D response element (VDRE), were able to confer bFGF inducibility on both a minimal osteocalcin and a heterologous promoter. These data suggest that induction of the human osteocalcin promoter by bFGF requires the interaction of more than one sequence element.

Animals↗