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Biomedical subjects

S Friedman

Publications and source records attributed to S Friedman.

At least 109 records · Page 6Linked to original sources

A carboxyl-terminal domain in fibroblast growth factor (FGF)-2 inhibits FGF-1 release in response to heat shock in vitro.

The fibroblast growth factor (FGF) prototypes, FGF-1 and FGF-2, lack a signal sequence, but both contain a nuclear localization sequence. We prepared a series of FGF-1 deletion mutants fused to the reporter gene, beta-galactosidase (beta-gal) and determined that a domain between residues 83 and 154 is responsible for FGF-1 cytosol retention in NIH 3T3 cells. Using a series of FGF-beta-gal chimeric proteins prepared by the shuffling of cassette-formatted synthetic FGF prototype genes, we were able to demonstrate that the nuclear localization sequence from the 5'-CUG region of FGF-2 is not able to direct the nuclear association of FGF-1 due to its inability to repress the function of the FGF-1 cytosol retention domain. We also observed that while the FGF-1:beta-gal chimera was released in response to heat shock, the FGF-2:beta-gal protein was not. Further, replacement of the FGF-1 cytosol retention domain with the corresponding domain from FGF-2 repressed the release of the chimeric protein. These data suggest that the specificity of the stress-induced secretion pathway for FGF-1 involves a carboxyl-terminal domain that is absent in FGF-2 and that the FGF-1 secretion pathway does not restrict the release of high molecular weight forms of FGF-1.

3T3 Cells↗

Comparison of injury during cadet basic training by gender.

OBJECTIVES: To describe the rate and distribution of injuries during basic training in male and female cadets and to assess the contribution of pretraining conditioning and height to the male-female differential in injuries. DESIGN: Cohort study. SETTING: The US Military Academy, West Point, NY. PARTICIPANTS: A total of 558 cadets from the class of 1995 at the US Military Academy. MAIN OUTCOME MEASURES: The rate of injuries resulting in 1 or more days excused from physical activities per 100 cadets and the rate of injuries resulting in hospitalization of 1 night or longer per 100 cadets. RESULTS: Women had 2.5 times the rate of injuries as men and 3.9 times the rate of injuries resulting in hospitalization. Women had significantly more stress fractures and stress reactions than men. The median number of days excused from physical activities for women's injuries was significantly higher than that from men's injuries. Pretraining conditioning, measured by performance on a 2-mile (3.2-km) run, accounted for approximately half the difference in rates of injuries between men and women; differences in height among men and women did not account for differences in injury rates. CONCLUSIONS: The women had a higher risk for injury during military training than men. Increased pretraining conditioning may substantially decrease the risk for injury.

Adolescent↗

Effect of the vaccines for children program on inner-city neighborhood physicians.

OBJECTIVE: To determine the probable effect of the Vaccines for Children (VFC) program on immunization coverage. DESIGN: Preintervention and postintervention study design, with data collected before and after enrollment in the VFC program. SETTING: Twenty-three inner-city neighborhood physicians' offices in New York City. PARTICIPANTS: In 1993, 30 physicians were randomly selected from 8 neighborhoods with the highest proportions of Medicaid-eligible individuals in New York City. In 1995-1996, the 30 physicians were contacted again. Twenty-three agreed to an interview and medical record review. Within each office, the medical records of children aged 3 to 35 months, with at least 3 visits in a 3-month or longer period, were randomly selected. Medical record reviews were conducted for 173 eligible children in 1993 and 528 in 1995-1996. INTERVENTIONS: The VFC program was implemented in October 1994. The administration fee increased from $2 to $17.85; physicians received vaccines free. MAIN OUTCOME MEASURES: Up-to-date status for immunizations and lead and tuberculosis screening; percentage of visits that are missed opportunities to immunize; and percentage of visits that were well-child visits. Up-to-date status, missed opportunities to immunize, and well-child visits were compared across time using chi 2 analysis, corrected for the use of cluster sampling. RESULTS: Up-to-date status changed significantly before and alter enrollment in the VFC program (P < .05) for all immunizations and for lead and tuberculosis screening. For the diphtheria toxoid, tetanus toxoid, and pertussis vaccine, oral poliovirus vaccine, and measles, mumps, and rubella vaccine combined, coverage increased from 17.9% to 42.2%, up by 24.3 percentage points (P < .05). Missed opportunities to immunize did not change, but well-child visits increased from 15.0% to 21.6% (P < .05). Physicians generally attributed performance improvements to the VFC program and not to other competing hypotheses. CONCLUSIONS: The VFC program seems to be responsible for an increase in immunization rates among these physicians.

Child, Preschool↗

Response to nutritional and growth hormone treatment in progeria.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare condition with an unknown molecular defect. Patients with HGP progressively develop failure to thrive (FTT), alopecia, loss of subcutaneous fat, scleroderma, stiffening of various joints, and severe atherosclerosis. The median life span is 13 years, and the main cause of death is cardiovascular complications. There are few reports of endocrine and metabolic studies because of the rarity of this condition, and the response to long-term growth hormone (GH) treatment has not been described. We report the results of endocrine and metabolic studies performed to investigate the etiology of growth failure in five patients with HGP. Additionally, the response to nutritional therapy (NT) and GH treatment in three of these patients is presented. Our results suggest that elevated GH levels are characteristic of this disease and that an elevated basal metabolic rate (BMR) could be the cause of the FTT seen in HGP. Nonaggressive NT slightly improved weight gain and growth velocity (GV). Combined NT and GH treatment in three patients improved the GV, increased the levels of growth factors, and paradoxically resulted in decreased BMRs. However, the response to these therapies decreased over time and did not seem to prevent the progression of atherosclerotic disease.

Adolescent↗

In vivo model for assessing the functional efficacy of endodontic filling materials and techniques.

Endodontic fillings were challenged with bacterial ingress in mandibular premolars of 4 beagle dogs. Groups 1, 2, and 3 (n = 9), had canals filled with gutta-percha and sealer, gutta-percha alone, and sealer alone, respectively. After 2 wk, pulp chambers were inoculated with plaque. Group 4 (n = 9) and group 5 (n = 5) had canals either filled as in groups 1 to 3 or unfilled, respectively, but not inoculated. Group 6 (n = 5) had canals unfilled and inoculated. Teeth were radiographed periodically for 14 wk, dogs terminated, and jaw blocks retrieved and processed for light microscopic examination. Rarefying osteitis appeared in group 6 at 3 wk and in groups 2, 3, and 5 at 11 wk. Periradicular inflammation was none, mild, or severe. Occurrence of severe inflammation in groups 1 to 6 was 0, 11%, 33%, 0, 60%, and 100%, respectively. Groups 1 to 3 combined differed significantly from group 4 (repeated-measures ANOVA, p < 0.05). This model could be used to assess the functional efficacy of endodontic fillings in vivo.

Animals↗

Retained foreign bodies.

OBJECTIVE: To evaluate the frequency of occurrence and outcome of patients having retained foreign bodies after treatment in an urgent-care setting. MATERIALS AND METHODS: Closed case records from the files of the Medical Professional Mutual Insurance Company involving claims of retained foreign body were reviewed for a 7-year period. MAIN RESULTS: Thirty-two patients filed 54 claims against 32 physicians and 22 health care institutions. Defense costs were $298,906, and indemnity payments were $1,279,171. Glass was the most frequent retained foreign body, constituting 53% of claims. Despite the fact that glass is radiopaque, x-ray films were ordered for only 35% of these patients. Retention of glass fragments when no radiologic study was obtained resulted in unsuccessful defense of 60% of the claims and higher indemnity payments. Radiologic studies were ordered for only 31% of all patients. CONCLUSIONS: All wounds should be considered to be at risk for foreign body entry. Documentation in the medical record of wound exploration and patient follow-up, and ordering of plain films and other diagnostic imaging studies should be used more frequently toward this end.

Diagnostic Errors↗

Characterization of the intergenic region which regulates the MspI restriction-modification system.

The 110-bp intergenic region between mspIM and mspIR, the genes encoding the MspI modification (M.MspI) and restriction (R.MspI) enzymes, respectively, was fused, in both orientations, with lacZ. Expression of a single-copy mspIM-lacZ fusion is more than 400-fold stronger than expression of an mspIR-lacZ fusion. M.MspI in trans represses expression of the mspIM-lacZ fusion by binding to the DNA but does not affect expression of the mspIR-lacZ fusion. Transcription start sites of the genes were identified, and a set of nonoverlapping promoters was assigned. DNase I footprinting showed that M.MspI binds to a site within the intergenic region that includes only the mspIM regulatory elements.

DNA Footprinting↗

Inhibition of growth factor mitogenicity and growth of tumor cell xenografts by a sulfonated distamycin A derivative.

Interference with growth factor-receptor interactions may have particular relevance in efforts to intervene clinically in both autocrine and paracrine aspects of malignancy. Suramin is a synthetic anticancer agent that works, in part, by blocking the binding of growth factors to their receptors. While initial clinical trials have been encouraging, its use in clinical applications is associated with significant toxicities. Suradista is a novel sulfonated distamycin derivative that is also effective at complexing and inactivating growth factors and cytokines while remaining relatively nontoxic. The goal of this study was to compare the antineoplastic properties of suramin and Suradista. To achieve this, the effects of these compounds on growth factor induced mitogenesis in normal mouse fibroblasts and human umbilical vein endothelial cells were examined, as well as their ability to inhibit the growth of NIH/3T3 cells that had been transformed by the introduction of a fibroblast growth factor (FGF) 1 coding region (residues 1-154) fused to the signal peptide of the hst/KS3 gene (sp-hst/KS3:FGF1-154). In each case, Suradista was more effective than suramin in inhibiting mitogenesis in normal cells, as well as the growth of the transformed cells. Furthermore, Suradista was also shown to be as effective as suramin at inhibiting the growth of sp-hst/KS3:FGF1-154-transformed NIH/3T3 xenografts grown in athymic nude mice when given at only 50% the dosage used for suramin (50 mg/kg for Suradista versus 100 mg/kg for suramin). In summary, these results indicate that novel compounds acting like suramin may be developed as effective antineoplastic agents and may also prove to be of clinical benefit.

3T3 Cells↗

On the "true-false" memory syndrome: the problem of clinical evidence.

A patient in twice-a-week psychoanalytic psychotherapy began to recover childhood memories of chronic sexual abuse, including oral, anal and genital penetration. These memories sometimes included bizarre content that created skepticism regarding their authenticity. However, this dubious quality was in marked contrast to the internal consistency, continuity, and emotional authenticity of the psychotherapeutic process. Criteria for attempting to distinguish between fantasy and reality are noted. Despite their tenuous nature, these criteria are important because, most frequently, they will be the only data available within the clinical situation.

Adult↗

Internal bleaching: long-term outcomes and complications.

Internal bleaching with a 30 percent hydrogen peroxide solution is aesthetically very successful in the short term; however, in the long term, the success rate falls below 50 percent. This procedure is associated with a risk of external root resorption, documented both clinically and experimentally. The etiology of resorption and the effects of 30 percent hydrogen peroxide on dental tissues suggest that this chemical should be avoided. Internal bleaching is possible using sodium perborate mixed with water. The aesthetic outcome is still acceptable and the potential for resorption may be minimized.

Borates↗

Treatment outcome of surgical and non-surgical management of endodontic failures.

The principal modalities available to manage endodontic treatment failures are orthograde retreatment and apical surgery. Both modalities have specific advantages, clinical implications, and risks, and their selection involves a complex decision-making process. A review of the literature pertaining to the treatment outcome of each modality was undertaken to establish an objective reference for practitioners involved in the management of endodontic treatment failures. Based on a weighted average calculation of the results reported in the reviewed studies, the orthograde retreatment of teeth associated with apical periodontitis results in a success rate of 66 per cent, an uncertain healing rate of 11 per cent, and a failure rate of 23 per cent. Apical surgery results in a success rate of 59 per cent, an uncertain healing rate of 22 per cent, and a failure rate of 19 per cent. These figures are discussed with reference to the characteristics of the reviewed studies. It appears that many of the reviewed studies have lesser relevance today, due to the current technical improvements in both treatment and modalities.

Apicoectomy↗

Isolated sleep paralysis in African Americans with panic disorder.

Isolated sleep paralysis (ISP) was assessed in African Americans and Whites diagnosed with panic disorder and other anxiety disorders. Participants were recruited from an outpatient clinic where they were diagnosed with panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, social phobia, and simple phobia. Control groups of volunteers without a history of psychiatric disorder were included. All research participants completed a questionnaire to assess for ISP. Group differences were analysed through a series of chi-square analyses. The incidence of recurrent ISP was significantly higher in African Americans with panic disorder (59.6%) as compared with African Americans with other anxiety disorders (11.1%), African American control group participants (23%), Whites with panic disorder (7.5%), Whites with other anxiety disorders (0%), and White control group participants (6%). Recurrent ISP was found to be more common among African American participants, particularly for those with panic disorder. African Americans with panic disorder may experience recurrent ISP as a feature of their disorder.

Adult↗

Elevated AGE-modified ApoB in sera of euglycemic, normolipidemic patients with atherosclerosis: relationship to tissue AGEs.

BACKGROUND: Advanced glycation endproducts (AGEs) are implicated in the pathogenesis of atherosclerotic vascular disease of diabetic and nondiabetic etiology. Recent research suggests that advanced glycation of ApoB contributes to the development of hyperlipidemia. AGE-specific receptors, expressed on vascular endothelium and mononuclear cells, may be involved in both the clearance of, and the inflammatory responses to AGEs. The aim of this study was to examine whether there is a relationship between serum AGE-ApoB and AGEs in arterial tissue of older normolipidemic nondiabetic patients with occlusive atherosclerotic disease, compared with age-matched and younger asymptomatic persons. MATERIALS AND METHODS: Serum AGE-ApoB was measured by ELISA in 21 cardiac bypass patients. Furthermore, an AGE-specific monoclonal antibody, and polyclonal antibodies against anti-AGE-receptor (anti-AGE-R) 1 and 2 were used to explore the localization and distribution of AGEs and AGE-R immunoreactivity (IR) in arterial segments excised from these patients. RESULTS: Serum AGE-ApoB levels were significantly elevated in the asymptomatic, older population, compared with those in young healthy persons (259 +/- 24 versus 180 +/- 21 AGE U/mg of ApoB, p < 0.01). Higher AGE-ApoB levels were observed in those patients with atherosclerosis (329 +/- 23 versus 259 +/- 24 AGE U/mg ApoB, p < 0.05). Comparisons of tissue AGE-collagen with serum AGE-ApoB levels showed a significant correlation (r = 0.707, p < 0.01). In early lesions, AGE-IR occurred mostly extracellularly. In fatty streaks and dense, cellular atheromatous lesions, AGE-IR was visible within lipid-containing smooth muscle cells and macrophages, while in late-stage, acellular plaques, AGE-IR occurred mostly extracellularly. AGE-R1 and -R2 were observed on vascular endothelial and smooth-muscle cells and on infiltrating mononuclear cells in the early-stage lesions, whereas in dense, late-stage plaques, they colocalized mostly with lipid-laden macrophages. On tissue sections, scoring of AGE-immunofluorescence correlated with tissue AGE and plasma AGE-ApoB. CONCLUSIONS: (1) The correlation between arterial tissue AGEs and circulating AGE-ApoB suggests a causal link between AGE modification of lipoproteins and atherosclerosis. AGE-specific receptors may contribute to this process. (2) Serum AGE-ApoB may serve to predict atherosclerosis in asymptomatic patients.

Adult↗

Experiences with ARTEMIS--an Internet-based telemedicine system.

ARTEMIS is one of the first systems to exploit the Internet/Intranet technologies for exchanging patient information among health care providers. The primary project goal was to develop and demonstrate a regional telehealth environment specifically to support real-time consultations among health care providers via a computer network, provide secure access to multi-media patient records and discharge summaries, facilitate authentication/digital sign-off, multi-media mail-based referrals, and network-based dictation/transcription. A prototype is deployed in southern West Virginia in a Community Care Network (CCN). The CCN consists of providers, hospitals, clinics, laboratories, that make up one "Virtual" clinic on the "Intranet". ARTEMIS employs new technologies such as Java and JavaScript for the browser, and CORBA-based "middleware" for interoperability at the server-end. Several experiments were designed for evaluating the impact of ARTEMIS on patient care. In this paper we discuss the challenges we faced and the means by which we plan to meet these challenges. We conclude by outlining new thrust areas in which we are concentrating in our next phase of development of ARTEMIS.

Computer Communication Networks↗