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Biomedical subjects

S Linn

Publications and source records attributed to S Linn.

At least 19 recordsLinked to original sources

Selective immunoneutralization of the multiple activities of Escherichia coli DNA polymerase I supports the model for separate active sites and indicates a complex 5' to 3' exonuclease.

DNA polymerase I (pol I) from Escherichia coli has three well-defined activities: DNA polymerase, 3'-5' exonuclease, and 5'-3' exonuclease. We have raised monoclonal antibodies to pol I which selectively neutralize each of these three activities, thus supporting the model of separate active sites for each activity, heretofore exclusively demonstrated with proteolytic fragments of pol I. Antibodies from each class could bind pol I in the presence of antibodies of another class, indicating the existence of significant spatial separation between each of the three sites. In addition, several of the neutralizing antibodies were able to distinguish particular activities of the 5'-3' exonuclease. One of them, for example, inhibited the RNase H activity but not the DNase activity. Two other antibodies could, in addition to inhibiting the polymerase and the 3'-5' exonuclease, either stimulate or inhibit the 5'-3' exonuclease depending upon the assay conditions, particularly the ionic strength.

Animals

Influence of cumulative sun exposure on the prevalence of common acquired nevi.

BACKGROUND: Conflicting evidence exists on the relation between sun exposure and the number of common acquired nevi. The increase in the number of common acquired nevi until early adulthood and their greater concentration on sun-exposed areas suggested that the growth of common acquired nevi is promoted by UV radiation. Nevertheless, it was noticed that although solar exposure accumulates with age, the number of common acquired nevi decreases after the third decade. OBJECTIVE: Our purpose was to examine the relation between the prevalence of common acquired nevi and accumulative sun exposure. METHODS: The number of common acquired nevi on 128 patients with multiple solar keratoses (SK) was compared with their number on 82 control subjects. The existence of SK served as a biologic marker for long-term solar effects. RESULTS: On patients with SK we counted 1285 nevi (mean 10.0 nevi per person) and on control subjects, 1521 nevi (mean 18.5 nevi) (p = 0.0046; Kruskal-Wallis test). The finding that persons exhibiting signs of accumulating sun effects have fewer nevi was maintained irrespective to differences of gender, occupation, and complexion. CONCLUSION: Our data suggest that accumulating solar effects may contribute to the natural maturation and elimination of common acquired nevi in late adulthood.

Aged

Biochemical heterogeneity in xeroderma pigmentosum complementation group E.

Cells from two patients with xeroderma pigmentosum complementation group E (XP-E) have been shown to lack an activity which binds specifically to UV-irradiated DNA (Chu and Chang, 1988). We investigated the occurrence of this binding activity in cell strains from nine additional, unrelated XP-E patients and found that all but one of these strains contained normal levels of the binding protein. Furthermore, the binding activity from these XP-E strains was indistinguishable from that of normal controls in thermal stability, behavior on ion-exchange chromatography, and electrophoretic mobility of protein-DNA complexes, indicating that there were no gross structural alterations in the protein. The association of XP-E with a deficiency in DNA-damage binding protein in cells from 3 of 12 XP-E patients (compared to 0 of 20 non-XP-E controls) is statistically significant (p less than 0.05), but there is no obvious correlation between the biochemical defect and the clinical or cellular characteristics of individual patients. Implications of these findings for the role of the binding protein in XP-E are discussed.

Cells, Cultured

DNA polymerase I modulates inducible stable DNA replication in Escherichia coli.

Mutants of Escherichia coli lacking RNase HI activity and cells induced for the SOS response express modes of DNA replication independent of protein synthesis, called constitutive and induced stable DNA replication, respectively. We report here that mutants deleted for the polA gene express induced stable DNA replication at approximately 25-fold the rate of wild-type cells, whereas constitutive stable DNA replication is not enhanced.

DNA Polymerase I

[Early vs delayed cholecystectomy for acute cholecystitis].

The timing of cholecystectomy in acute cholecystitis is still controversial. A marked change toward early surgery has been noted in the past decade. In a retrospective study of 197 patients we evaluated the results of cholecystectomy in 117 who underwent elective cholecystectomy, and in 80 operated on during the acute phase of cholecystitis. The diagnosis of acute cholecystitis was by isotope scan (HIDA) or ultrasound. There was no case of misdiagnosis. 3 patients died postoperatively: 2 in the early operation group (1 had emergency cholecystectomy) and 1 in the elective group. Postoperative complications were more frequent in the early surgery group (p = 0.06). The highest morbidity was in early cholecystectomy in those older than 60 years who had cardiovascular disease (p less than 0.0002). Hernia in the scar was a unique complication of the early operation. According to most studies reviewed, early operation eliminates the need for emergency operation when conservative treatment fails, without increasing morbidity or mortality. Therefore, early operation during the acute phase of cholecystectomy is advised. For patients older than 60 years who have cardiovascular disease, we recommend delaying surgery until the acute inflammation subsides. The waiting period before surgery should be as short as possible in order to reduce the risk of recurrent cholecystitis and its complications.

Acute Disease

Seborrheic skin and acne vulgaris as protective factors against the development of basal cell epithelioma.

This study was conducted in order to evaluate a possible protective role of seborrheic complexion and a history of acne on the development of basal cell epithelioma (BCE). For this purpose, 77 patients with this tumor were examined and asked to fill out a questionnaire. The questionnaire included demographic data and questions about skin type, eye and hair colors, sun exposure habits and a past history of acne. The nature, number and location of tumors, the texture of skin and acne scars were noted by a physician. A group of 93 age-, sex- and skin-color-matched patients served as controls. The results show a clear relationship between seborrheic features and a lower risk of developing BCE, after controlling for solar exposure using the Mantel-Haenszel summary measure. The same trend was found in patients with a history of acne. Whether ultraviolet light absorption by sebum, an anticancer activity of Propionibacterium acnes or other factors play a protective role against the development of BCE is as yet unclear.

Acne Vulgaris

Serum total cholesterol: HDL cholesterol ratios in US white and black adults by selected demographic and socioeconomic variables (HANES II).

BACKGROUND: Framingham Study findings suggest that total cholesterol (TC):High density lipoprotein cholesterol (HDL-C) ratio is a useful summary of the joint contribution of TC and HDL-C to coronary heart disease (CHD) risk. Information on the distribution of TC:HDL-C in the US population is limited to selected populations and the relationship of the ratio distribution and its correlates has received little attention. METHOD: TC/HDL-C ratios were examined in a representative sample of the United States adult population ages 20 to 74 years, between February 1976 and February 1980 during NHANES II, using stratification and multivariate regression analyses. RESULTS: Age-adjusted mean ratios were higher in men compared with women and were higher in Whites compared with Blacks. White men had the highest TC/HDL-C mean ratios. These relationships remained after stratification by age, education, body mass index, alcohol use, cigarette smoking, and physical activity. Using multivariate analyses, the ratios were positively related to BMI, age, and smoking; and negatively related to female sex, alcohol use, being Black, and physical activity. CONCLUSIONS: Using a ratio reference point of greater than or equal to 4.5 from the Framingham study, at least an estimated 44 million persons ages 25 to 74 years in the US were found to be at higher risk of developing coronary heart disease.

Adult

The association between skull fracture, intracranial pathology and outcome in pediatric head injury.

We prospectively studied 653 consecutive head-injured children (less than or equal to 14 years old) treated over a 54-month period (1984-88) at the Department of Neurosurgery of the Rambam Medical Center (Haifa, Israel). Demographic and clinical data were collected, the patients were divided into five age groups (birth to 2 years, 169; 3-5 years, 194; 6-9 years, 164; 10-12 years, 77; and 13-14 years, 49), and the information relative to each was then compared. All patients (except three who died on the operating table) underwent computed tomography (CT) scans; 225 (34.6%) had intracranial pathology, e.g. focal mass lesions, diffuse axonal injury, and subarachnoid haemorrhage. The rate of detected pathology increased with age. Skull fracture was documented in 468 (72%) patients. Craniotomies were done on 114 (17.5%) patients. After 3 months, the patients were classified as having good recovery (84.8%), moderate disability (5.5%), or severe disability (2.3%); 0.9% were in a vegetative state. The mortality was 6.6% (43 patients); of these, 39 (90.7%) had admission Glasgow Coma Scale scores below 8. In our area the annual incidence of neurosurgical hospitalization due to head injury in the pediatric group was 37.6 per 100,000 inhabitants per year. This study substantiates the findings of other series on the effects of prognosis of factors such as associated trauma, admission Glasgow Coma Score, mass lesions with persistent intracranial pressure elevation, or diffuse axonal injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Penetrating craniocerebral injuries in civilians.

During a 6-year period (1984-89), 31 patients were treated at Rambam Medical Center with penetrating craniocerebral injuries (PCCI) not associated with military action. Eighteen (58%) patients died during their initial hospitalization; only two of them had admission Glasgow Coma Scale (GCS) above five. The admission GCS coupled with the mode of injury (type of missile and motivation of shooting) were valuable for early accurate prognosis assessment. Patients with admission GCS of 3 and 4 invariably died despite rapid treatment and attempted haematoma evacuation. The neurological status, CT appearance, as well as the motivation of shooting should be considered in order to assess accurately the possible outcome. Compared with our military series of 113 patients with PCCI, there were more extensive injuries, although the mean period until neurosurgical treatment was the same. Long-term complications connected to dural tears remote from the entrance wound occurred in three of the survivors.

Adolescent

Seasonal variation in growth during growth hormone therapy.

Seasonal variation in growth of normal children has been well described, although the mechanism by which it occurs has not been elucidated. The growth of 52 growth hormone-deficient children treated with synthetic human growth hormone was analyzed. A similar seasonal variation was observed, with mean (+/- SEM) peak growth occurring in the summer (8.2 +/- 0.3 cm/y) and winter (7.7 +/- 0.2 cm/y), and trough growth occurring in the autumn (6.9 +/- 0.3 cm/y). Forty-seven percent of subjects grew minimally during the autumn, and only two children showed peak growth in that season. Individual variations between maximal and minimal growth seasons amounted to 3.5 +/- 0.3 cm/y. The seasonal pattern was statistically significant for the group as a whole, for the prepubertal subgroup, and for the boys. The variation persisted when the first year of treatment was excluded to avoid bias of the initial growth spurt. The season of onset of therapy did not affect total growth during the first year. The demonstration of a seasonal pattern in growth of these children suggests that the seasonal variation may be mediated by peripheral rather than central factors. Paired clonidine-provoked growth hormone levels and an integrated concentration of 24-hour growth hormone levels and serum levels of insulinlike growth hormone I measured in a control group of normally growing children were also analyzed and showed no seasonal variation. This further suggests that peripheral rather than central factors are responsible for the seasonal variation in children's growth.

Adolescent

Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease.

To determine the associations of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol with mortality from coronary heart disease and cardiovascular disease, we studied 2541 white men who were 40 to 69 years old at base line and followed them for an average of 10.1 years. Seventeen percent had some manifestation of cardiovascular disease at base line, whereas the others did not. Among the men who had cardiovascular disease at base line, we found, after multivariate adjustment, that those with "high" blood cholesterol levels (above 6.19 mmol per liter) had a risk of death from cardiovascular disease, including coronary heart disease, that was 3.45 times higher (95 percent confidence interval, 1.63 to 7.33) than that for men with "desirable" blood cholesterol levels (below 5.16 mmol per liter). The corresponding hazard ratios were 5.92 (95 percent confidence interval, 2.59 to 13.51) for LDL cholesterol levels above 4.13 mmol per liter as compared with those below 3.35 mmol per liter, and 6.02 (95 percent confidence interval, 2.73 to 13.28) for HDL cholesterol levels below 0.90 mmol per liter as compared with those above 1.16 mmol per liter. All three lipid levels were also significant predictors of death from coronary heart disease alone (P less than 0.005). Total cholesterol and LDL cholesterol levels were also significant predictors of death from cardiovascular and coronary heart disease in men without preexisting cardiovascular disease, although at a lower level of absolute risk of death. Thus, the 10-year risk of death from cardiovascular disease for a man with preexisting cardiovascular disease increased from 3.8 percent to almost 19.6 percent with increasing levels of total cholesterol from "desirable" to "high," whereas the corresponding risk for a man who was free of cardiovascular disease at base line increased from 1.7 percent to 4.9 percent. Our findings suggest that total, LDL, and HDL cholesterol levels predict subsequent mortality in men 40 to 69 years of age, especially those with preexisting cardiovascular disease.

Adult

[Head and brain injuries in bicyclists].

44 patients were hospitalized for neurosurgical care after bicycle accidents during a period of 50 months. Ten times as many were injured in other types of road accidents. 42 of the 44 cases had brain injury, with a mean hospitalization of 9.7 days. A third needed operation and a fourth were discharged with residual neurological deficits. The low incidence of 0.95 cases per 100,000 per year led us to examine the factors which limit the use of bicycles in our region. The severity of the injuries in our cases was much greater than in those in other countries, with a mean injury severity score of 14.2. None of our cases had worn a protective helmet, and we join in the world-wide plea for an educational campaign for their use.

Bicycling

Mammalian mitochondrial endonuclease activities specific for ultraviolet-irradiated DNA.

Mitochondrial forms of uracil DNA glycosylase and UV endonuclease have been purified and characterized from the mouse plasmacytoma cell line, MPC-11. As in other cell types, the mitochondrial uracil DNA glycosylase has properties very similar to those of the nuclear enzyme, although in this case the mitochondrial activity was also distinguishable by extreme sensitivity to dilution. Three mitochondrial UV endonuclease activities are also similar to nuclear enzymes; however, the relative amounts of these enzyme activities in the mitochondria is significantly different from that in the nucleus. In particular, mitochondria contain a much higher proportion of an activity analogous to UV endonuclease III. Nuclear UV endonuclease III activity is absent from XP group D fibroblasts and XP group D lymphoblasts have reduced, but detectable levels of the mitochondrial form of this enzyme. This residual activity differs in its properties from the normal mitochondrial form of UV endonuclease III, however. The presence of these enzyme activities which function in base excision repair suggests that such DNA repair occurs in mitochondria. Alternatively, these enzymes might act to mark damaged mitochondrial genomes for subsequent degradation.

Animals

DNA polymerases alpha, delta, and epsilon: three distinct enzymes from HeLa cells.

DNA polymerases alpha, delta, and epsilon have been purified and characterized from the same HeLa cell extract in order to determine their relationship by comparing them from the same cell type. The catalytic properties and the primary structures of the large subunits of the DNA polymerases as compared by partial peptide mapping with N-chlorosuccinimide are different. Likewise, the small subunit of DNA polymerase epsilon appears to be distinct from the large subunit of the same polymerase and from the smaller subunits of DNA polymerase alpha. HeLa DNA polymerase delta is processive only when HeLa proliferating cell nuclear antigen is present, whereas DNA polymerase epsilon is quite processive in its absence. Inhibitor and activator spectra of DNA polymerases alpha, delta, and epsilon also distinguish the three enzymes. These results and immunologic comparisons published elsewhere support the premise that HeLa DNA polymerases alpha, delta, and epsilon are distinct enzymes that have common properties with yeast DNA polymerases I, III, and II, respectively.

Autoantigens

Head trauma in northern Israel: incidence and types.

A descriptive epidemiological study of neurotraumatology was undertaken over a 4.5-year period at a regional hospital with a referral base of 1,200,000 residents served by a single neurosurgical department. Neurosurgical evaluations and treatments were given to 1,370 patients in this period. The data base consists of demographic, clinical and radiological features at the time of admission, as well as the hospital course through discharge. The crude incidence rate was 25.2 +/- 3.1 cases per 100,000 person-years (similar to that of three neurosurgical units in Scotland). Age adjustment showed almost twice this rate at the two extremes of age and a smaller elevation in early adulthood. The crude incidence was 36.9 for males and 13.4 for females (p less than 0.01). Age-specific incidence rates in Jews compared to other ethnic groups were reported. Falls had an incidence of 12.8 (51%), road accidents 9.0 (35.7%) and assaults 2.3 (9%) per 100,000 person-years. Other causes were accidents during work or sport and suicide. The rate of brain pathology as revealed by computerized tomography steadily increased from 19% in childhood to 71% in the elderly with a mean of 41.8%. A similar increasing trend with age was found in the rate of intracranial mass lesions (mean 28.3%), impaired consciousness (30.4%) and mortality (13%).

Adolescent