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Biomedical subjects

S Friedman

Publications and source records attributed to S Friedman.

At least 19 recordsLinked to original sources

Analysis of endogenous and exogenous nuclear translocation of fibroblast growth factor-1 in NIH 3T3 cells.

Nuclear localization of fibroblast growth factors (FGF) have been reported by many laboratories. We demonstrate here that FGF-1, the precursor for acidic FGF contains a putative nuclear translocation sequence (NTS) NYKKPKL, which is able to direct the expression of the bacterial beta galactosidase (beta gal) gene to the nucleus of transfected NIH 3T3 cells. However, this NTS is unable to target either FGF-1 itself or a FGF-1-beta gal fusion protein into the nucleus, suggesting that FGF-1 may contain an additional sequence which prevents endogenously expressed FGF-1 from being translocated into the nucleus. Indeed, when FGF-1 was fused to the NTS derived from the yeast histone 2B gene, the chimeric construct also failed to be transported into the nucleus either by itself or as a beta gal fusion protein. Interestingly, when 125I-FGF-1 was used to stimulate quiescent NIH 3T3 cells, a significant amount of internalized 125I-FGF-1 (approximately 10%) was found within the nucleus and the nuclear localization of FGF-1 through the exogenous pathway could be significantly reduced by suramin, an inhibitor of the interaction of FGF-1 with its receptor. These data suggest that while FGF-1 contains a NTS, nuclear translocation requires an exogenous and not an endogenous pathway.

3T3 Cells

Heat shock induces the release of fibroblast growth factor 1 from NIH 3T3 cells.

Fibroblast growth factor 1 (FGF-1) is a potent angiogenic and neurotrophic factor whose structure lacks a classical signal sequence for secretion. Although the initiation of these biological activities involves the interaction between FGF-1 and cell surface receptors, the mechanism responsible for the regulation of FGF-1 secretion is unknown. We report that murine NIH 3T3 cells transfected with a synthetic gene encoding FGF-1 secrete FGF-1 into their conditioned medium in response to heat shock. The form of FGF-1 released by NIH 3T3 cells in response to increased temperature (42 degrees C, 2 hr) in vitro is not biologically active and does not associate with either heparin or the extracellular NIH 3T3 monolayer matrix. However, it was possible to derive biologically active FGF-1 from the conditioned medium of heat-shocked NIH 3T3 cell transfectants by ammonium sulfate fractionation. The form of FGF-1 exposed by ammonium sulfate fractionation is similar in size to cytosolic FGF-1 and can bind and be eluted from immobilized heparin similarly to the recombinant human FGF-1 polypeptide. Further, the release of FGF-1 by NIH 3T3 cell transfectants in response to heat shock is reduced significantly by both actinomycin D and cycloheximide. These data indicate that increased temperature may upregulate the expression of a factor responsible for the secretion of FGF-1 as a biologically inactive complex that requires an activation step to exhibit the biological activity of the extracellular polypeptide mitogen.

3T3 Cells

Binding of the EcoRII methyltransferase to 5-fluorocytosine-containing DNA. Isolation of a bound peptide.

The properties of the interaction of 5-fluorocytosine-containing DNA with the EcoRII methyltransferase were studied. The DNA used was either a polymer synthesized in vitro, or a 20-mer containing one CCA/TGG sequence. The DNA could be methylated by the enzyme. In the process the enzyme formed a tight binding adduct with the DNA that could be identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Enzyme activity was inhibited by this interaction. The 20-mer could be used to titrate the active site of the enzyme. The DNA polymer formed a tight binding complex that could be identified following digestion of the DNA with pancreatic deoxyribonuclease or micrococcal nuclease. A peptide-DNA adduct could be isolated after digestion of the EcoRII-DNA adduct with staphylococcal protease V8 by high pressure liquid chromatography and polyacrylamide gel electrophoresis. Sequencing of the peptide indicated the DNA bound to a region of the protein that is conserved in all procaryotic DNA(cytosine-5)-methyltransferases. We have previously shown that this region contains a cysteine that can be photomethylated with adenosylmethionine. This region, in addition to forming part of, or being adjacent to, the AdoMet binding site, also forms part of the DNA binding site.

Amino Acid Sequence

Prevalence of minor congenital anomalies in newborns of diabetic mothers.

Minor congenital anomalies (MCA) were assessed in the offspring of 802 gestational diabetic mothers, 117 pre-gestational diabetic mothers, and 380 offspring born to normal mothers. The prevalence of infants with MCA ranged between 19.4% and 20.5% in the three groups without any significant difference between them. There was no correlation between the prevalence and type of MCA and the severity of the diabetic state. Neither was there any correlation between the prevalence or type of MCA and the appearance or type of major congenital anomalies.

Abnormalities, Multiple

Tissue response following CO2 laser application in apical surgery: light microscopic assessment in dogs.

The potential advantages of CO2 laser in apical surgery have not been established histologically. Therefore, the long-term effects of CO2 laser on the apical and periapical tissues were examined histologically in dogs 6 months after apical surgery. Lased specimens and unlased controls showed periapical inflammatory and osteogenic reactions. Lased root surfaces revealed craters with a superficial charred layer closely associated with new cementum-like matrix. The subjacent dentin appeared tubule-free and eosinophilic. Lased bone trabeculae showed a charred layer with a deeper osteocyte-free zone. The charred layer was covered by new bone. Detached charred segments in the marrow space and periapical inflammatory infiltrate were intimately associated with multinucleated giant cells, some containing minute char particles. Such cells were absent from the root and trabecular char linings. In addition, the charred surfaces were free of hard tissue resorption. These results suggest that CO2 laser does not hinder healing when applied in apical surgery.

Alveolar Process

Prenatal diagnosis of familial congenital pyloric atresia.

Familial congenital pyloric atresia is a rare malformation of the fetal gastrointestinal tract. It usually manifests as maternal polyhydramnios and enlarged fetal stomach on ultrasound scan. Sonographic prenatal diagnosis and management of a pregnancy complicated by familial congenital pyloric atresia are presented.

Adult

Efficacy of removing glass ionomer cement, zinc oxide eugenol, and epoxy resin sealers from retreated root canals.

Removal of gutta-percha and various sealers was assessed during retreatment of the root canal system. Sixty root canals were prepared and obturated with gutta-percha and Ketac-endo, Roth's 801 cement, or AH26. After 14 days, the canals were retreated by hand or ultrasonic technique and the retreatment time was recorded. The roots were split and the amount of debris that remained on the canal walls in three separate levels was recorded by use of a dissecting microscope. The mean scores were compared by one-way and two-way ANOVA. The total score was significantly the highest for Ketac-endo (p less than 0.04), followed by AH26 and Roth's 801 cement. The largest amount of debris was consistently found in the apical third, and generally it was comparable for both retreatment techniques. The ultrasonic technique was significantly faster than the hand technique for all sealers tested (p less than 0.0004, p less than 0.0003, p less than 0.02, respectively). Hand retreatment of Ketac-endo was the slowest, whereas ultrasonic retreatment of Roth's 801 cement was the fastest. The results indicated that Ketac-endo endodontic sealer can be effectively removed from the root canal by ultrasonic instrumentation.

Analysis of Variance

Active and passive P3 latency and psychometric performance: influence of age and individual differences.

The relationship of P3 latency of the event-related potential (ERP) to psychometric performance was investigated in 41 subjects who ranged in age from 20 to 88 years. P3 responses were recorded from subjects using an auditory oddball paradigm with and without task-demands. Subjects also received psychometric tests of verbal performance, visuospatial performance, concentration, and immediate, recent and remote memory. Factor analysis was used to reduce the set of psychometric measures to four factors (Verbal learning, general intelligence, narrative recall/fluency, and concentration). Both passive and active P3 latency showed a linear increase with age. Age was inversely correlated with verbal learning performance. After accounting for the influence of age, passive P3 latency correlated with the psychometric factor associated with narrative recall and verbal fluency. Active P3 latency was correlated with factors reflecting general intelligence and concentration. These findings suggest that cognitive processing speed contributes to psychometric performance in adults. The psychological or biological basis for this relationship remains to be identified.

Adult

Obsessive-compulsive disorder in patients with chronic pruritic conditions: case studies and discussion.

BACKGROUND: Relatively few persons with obsessive-compulsive disorder (OCD) come to psychiatric clinics for treatment. Our hypothesis was that patients with a form of OCD that involves compulsive hand and body washing might initially seek treatment from a dermatologist. OBJECTIVE: Our purpose was to screen patients attending a dermatology clinic to determine the frequency of OCD cases and to help dermatologists recognize this disorder. METHODS: Randomly selected patients who presented with one of several chronic pruritic conditions were interviewed to determine the presence of anxiety disorders. RESULTS: A significantly high percentage of the patients (14%) were found to have previously undiagnosed OCD. Case studies of five of these patients are presented. CONCLUSION: A significant number of patients with undiagnosed OCD appear to present to dermatology clinics. Identification and referral for psychiatric consultation may aid in the treatment of both OCD and concomitant dermatologic conditions.

Adult

Prevalence of dust mites in the homes of people with asthma living in eight different geographic areas of the United States.

The density and species prevalence of dust mites were determined at various times over a 5-year-period in 252 homes of dust mite sensitive people with asthma who lived in eight geographic areas of the United States (Cincinnati, Ohio; New Orleans, La.; Memphis, Tenn.; Galveston, Texas; Greenville, N.C.; Delray Beach, Fla.; San Diego and Los Angeles, Calif.). The most common dust mites found in the homes were Dermatophagoides farinae (DF), D. pteronyssinus (DP), Euroglyphus maynei (EM), and Blomia tropicalis. All homes in all locations contained Dermatophagoides spp. mites, but few homes were populated exclusively by either DF or DP alone. Most homes (81.7%) were coinhabitated by both DF and DP. In coinhabited homes one species was predominant and usually made up at least 75% of the total mite population. Prevalence of the dominant or only species present varied between homes within a geographic area. EM occurred in significant numbers in 35.7% of homes in New Orleans, Memphis, Galveston, Delray Beach, and San Diego. Blomia tropicalis occurred in these same cities but in low densities. For all dust samples, only 13 homes of the 252 sampled had 100 or fewer mites/gm dust, which is considered to be the threshold for sensitivity. Most homes had average mite densities of 500 or more mites/gm dust. The results of the present study suggest a significant and widespread occurrence of both DF and DP. Therefore extracts of both mite species should be considered for diagnostic tests and immunotherapy. Significant levels of EM were present in some areas. Thus sensitivity to EM should be considered in these areas.

Adolescent

Endodontic retreatment: a rational approach to root canal reinstrumentation.

During nonsurgical endodontic retreatment, endodontic instruments are forced apically to remove the root canal filling material and regain canal patency. Undiscriminating burrowing down the canal in the apical direction may be fruitless and harmful. To avoid complications, the dentin overhanging the canal orifice must be removed and an unobstructed access established to the root filling material, so as to facilitate its removal. Reinstrumentation of the filled canal must take into consideration the nature of the filling material and the physical properties of endodontic instruments, as well as the dynamic aspects of canal preparation. This article discusses the mechanical considerations pertaining to root canal retreatment and outlines a step by step rationale approach to retreatment.

Dental Cavity Preparation

Effect of different endodontic treatment protocols on periodontal repair and root resorption of replanted dog teeth.

This study examined, histologically, the healing of intentionally damaged root surfaces of replanted teeth with either uninfected or infected root canals treated with short- and long-term calcium hydroxide. Thirty beagle dog incisors were randomly divided into four groups. In group 1, uninfected obturated incisors were extracted, the roots were longitudinally grooved and the teeth were replanted within 2 min. In group 2 the root canals were artificially infected followed by extraction, longitudinal grooving, and replantation as described in group 1. Fourteen days after replantation, the root canals were fully instrumented and medicated with intracanal calcium hydroxide. One week later the root canals were permanently obturated with gutta-percha and sealer. The teeth in group 3 were treated as described in group 2 but after 1 wk the calcium hydroxide dressing was repacked for the duration of the study. In group 4 (positive control) the teeth were treated as described in groups 2 and 3 but no endodontic treatment was performed. After 8 wk, sacrifice and histological preparation were carried out. In group 1 complete cemental repair was seen in all teeth. In groups 2 and 3, complete and incomplete cemental repair was seen in seven and two teeth, respectively. An ankylotic area was present in one tooth in group 3. None of the teeth in group 4 showed cemental repair. It was concluded that short- and long-term calcium hydroxide treatment resulted in similar healing patterns when endodontic treatment is initiated 14 days after replantation of teeth.

Animals

Incidence of interappointment emergency associated with endodontic therapy.

Endodontic interappointment emergency (EIE) occurs in a low incidence following treatment by qualified operators. The purpose of this study was to assess the incidence of EIE after treatment by undergraduate students and to examine its correlation with preoperative and operative parameters. Randomly selected 334 records were retrospectively surveyed for unscheduled emergency appointments following endodontic treatment by undergraduate students. Treatment included step-back canal preparation in multiple visits with formocresol interappointment dressing. The incidence of EIE was 4.2%, and unrelated to the patients' sex and age or to tooth location. It was significantly higher in nonvital than in vital teeth (p < 0.05), with the highest occurrence in nonvital teeth unassociated with periapical radiolucency. Clinically, EIE was associated with swelling in half of the cases. It is concluded that the incidence of EIE following treatment by undergraduate students is low and related to tooth vitality.

Acute Disease

Periodontal healing of replanted dog teeth stored in Viaspan, milk and Hank's balanced salt solution.

This study examined, histologically, periodontal healing and root resorption of replanted dogs teeth stored in Viaspan for different time periods and compared these healing patterns to those after storage in milk or Hank's balanced salt solution (HBSS). Seventy-two beagle incisors were endodontically treated, extracted, randomly divided and placed in Viaspan or milk for 6, 12, 24 and 36 h, and Viaspan or HBSS for 36, 48, 72 and 96 h, after which they were replanted. Four negative control teeth were immediately replanted while four positive controls were allowed to dry for one hour before replantation. All replanted teeth were splinted for 14 days. Two months after replantation the dogs were killed and the teeth histologically examined for healing of the supporting tissues. For Viaspan neither replacement nor inflammatory root resorption was seen after 6 and 12 h storage. A statistically significant rise in the incidence of replacement resorption was seen at 24, 36 and 48 h which decreased again at 72 and 96 h to levels equal to storage for 6 and 12 h. The occurrence of inflammatory root resorption was low and significantly increased only at 48 h after which it decreased significantly again. Viaspan proved superior to milk as a storage medium. Teeth stored in HBSS showed healing results similar to those stored in Viaspan.

Adenosine

Effects of sodium lactate infusion on cisternal lactate and carbon dioxide levels in nonhuman primates.

OBJECTIVE: To further the understanding of lactate-induced panic in patients with panic disorder, the authors examined cisternal lactate and carbon dioxide levels in nonhuman primates after infusions of sodium lactate comparable to those used in studies of human beings. METHOD: CSF and venous blood lactate, pH, PCO2, PO2, and bicarbonate were measured in five ketamine-anesthetized nonhuman primates, without mechanical ventilation, before and after they underwent infusions of sodium lactate. In addition, the same measurements were made for three of the five subjects who were given saline infusions. RESULTS: Despite the development of the characteristic peripheral biochemical effects of infused sodium lactate--increased lactate and bicarbonate levels and metabolic alkalosis--no increases in central lactate or carbon dioxide levels were observed. Saline infusions produced no biochemical effects on venous and cisternal measures. CONCLUSIONS: The results of this study are in keeping with previous findings of nonpermeability of the blood-brain barrier to anionic compounds such as lactate. They therefore support theories of lactate panic based on cognitive and/or brainstem misevaluation of peripheral somatic sensations.

Animals

Suicidal ideation and suicide attempts among patients with panic disorder: a survey of two outpatient clinics.

OBJECTIVE: Recent epidemiologic studies found that 20% of subjects with the diagnosis of panic disorder had attempted suicide. This study sought to determine the prevalence of suicidal ideation and suicide attempts among patients with panic disorder and whether the presence of comorbid borderline personality disorder influenced the prevalence of suicidal thoughts and behavior. METHOD: At two outpatient clinics, experienced clinicians conducted retrospective reviews of data from the intake interviews and charts of 59 patients with panic disorder and comorbid borderline personality disorder and 234 patients with panic disorder with or without axis II disorders other than borderline personality disorder. RESULTS: Suicide attempts were reported by 2% of the patients with panic disorder, compared to 25% of the patients with both panic disorder and borderline personality disorder. In addition, 2% of the patients with panic disorder, compared to 27% of the patients with panic disorder and borderline personality disorder, reported suicidal ideation that was judged to be of clinical significance. CONCLUSIONS: The rate of suicidal ideation and suicide attempts for psychiatric outpatients with panic disorder was discrepant with the findings of the earlier studies. The increased suicide risk in this group of patients was associated with borderline personality disorder, increased substance abuse, and affective instability. While 61% of the panic disorder patients and 78% of the patients with both panic disorder and borderline personality disorder reported thinking about death, this must be distinguished from actual suicidal ideation and clinical risk of suicide.

Adult