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Biomedical subjects

S Henderson

Publications and source records attributed to S Henderson.

At least 127 records · Page 7Linked to original sources

New modalities under development for adhesion prevention: immunomodulatory agents and poloxamer barrier materials.

Obviously, no single modality will prove to be universally applicable or completely effective at preventing postoperative adhesion formation. Increasing understanding of the pathophysiology of peritoneal healing provides the intellectual basis for the development of specific interventions at critical points along the adhesion formation cascade. We believe that multimodality therapy, including the use of pharmacologic adjuvants such as immunomodulatory drugs and fibrinolytic/anticoagulant agents in conjunction with a barrier material tailored to the specific operative procedure may provide optimal results. Hopefully, developments in the 1990's will provide reproductive surgeons with the means to help patients derive maximal benefit from their reconstructive procedures.

Adjuvants, Immunologic↗

Reaction time and movement time in children with a Developmental Coordination Disorder.

The Test of Motor Impairment (TOMI) was used to select 12 children with a Developmental Coordination Disorder (DCD) and 12 age-matched controls. In an aiming task, movement latency, movement duration and its variability were significantly prolonged in the DCD group. In a coincidence timing version of the task, absolute timing error was significantly greater in the DCD group. The most robust chronometric effect for differentiating the two groups seemed to be the duration of movement when the target was small. Multiple regression showed that TOMI was a powerful indicator of movement duration.

Child↗

The Epstein-Barr virus (EBV) nuclear antigen 1 BamHI F promoter is activated on entry of EBV-transformed B cells into the lytic cycle.

In Epstein-Barr virus (EBV)-positive Burkitt's lymphoma cell lines exhibiting the latency I form of infection (i.e., EBV nuclear antigen 1 [EBNA1] positive in the absence of other latent proteins), the EBNA1 mRNA has a unique BamHI Q/U/K splice structure and is expressed from a novel promoter, Fp, located near the BamHI FQ boundary. This contrasts with the situation in EBV-transformed lymphoblastoid cell lines (LCLs) exhibiting the latency III form of infection (i.e., positive for all latent proteins), in which transcription from the upstream Cp or Wp promoters is the principal source of EBNA mRNAs. We carried out cDNA amplifications with oligonucleotide primer-probe combinations to determine whether Fp is ever active in an LCL environment. The results clearly showed that some LCLs express a Q/U/K-spliced EBNA1 mRNA in addition to the expected Cp/Wp-initiated transcripts; this seemed inconsistent with the concept of Cp/Wp and Fp as mutually exclusive promoters. Here we show that Fp is indeed silent in latency III cells but is activated at an early stage following the switch from latency III into the virus lytic cycle. Four pieces of evidence support this conclusion: (i) examples of coincident Cp/Wp and Fp usage in LCLs are restricted to those lines in which a small subpopulation of cells have spontaneously entered the lytic cycle; (ii) transcripts initiating from Fp can readily be demonstrated in spontaneously productive lines by S1 nuclease protection; (iii) the presence of Fp-initiated transcripts is not affected by acyclovir blockade of the late lytic cycle; and (iv) infection of latently infected LCLs with a recombinant vaccinia virus encoding the EBV immediate-early protein BZLF1, a transcriptional transactivator which normally initiates the lytic cycle, results in the appearance of the diagnostic Q/U/K-spliced transcripts.

Antigens, Viral↗

General practitioners' reported knowledge about depression and dementia in elderly patients.

Previous studies have shown that general practitioners often fail to detect dementia and depression in their elderly patients. The present study aimed to find out how much knowledge general practitioners have of these disorders. The knowledge of 36 general practitioners was assessed and it was found that they had a limited knowledge of the symptoms and signs of dementia and depression. Furthermore, almost 60% of the general practitioners did not know that Alzheimer's disease is the most common dementing disorder.

Aged↗

Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death.

Epstein-Barr virus (EBV) not only induces growth transformation in human B lymphocytes, but has more recently been shown to enhance B cell survival under suboptimal conditions where growth is inhibited; both effects are mediated through the coordinate action of eight virus-coded latent proteins. The effect upon cell survival is best recognized in EBV-positive Burkitt's lymphoma cell lines where activation of full virus latent gene expression protects the cells from programmed cell death (apoptosis). Here we show by DNA transfection into human B cells that protection from apoptosis is conferred through expression of a single EBV latent protein, the latent membrane protein LMP 1. Furthermore, we demonstrate that LMP 1 mediates this effect by up-regulating expression of the cellular oncogene bcl-2. The interplay between EBV infection and expression of this cellular oncogene has important implications for virus persistence and for the pathogenesis of virus-associated malignant disease.

Antigens, Viral↗

Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis.

Epstein-Barr virus (EBV), a human herpesvirus, establishes a persistent asymptomatic infection of the circulating B-lymphocyte pool. The mechanism of virus persistence is not understood but, given the limited lifespan of most B cells in vivo, it seems most likely that EBV-infected cells must gain access to the long-lived memory B-cell pool. Here we show in an in vitro system that EBV, through expression of the full set of eight virus-coded 'latent' proteins, can protect human B cells from programmed cell death (apoptosis), the deletion mechanism which normally restricts entry into memory. We have found that EBV-positive Burkitt's lymphoma (BL) cell clones retaining the original tumour cell phenotype and expressing only one of the virus latent proteins, the nuclear antigen EBNA 1, are extremely sensitive to apoptosis; in this respect they resemble the tumour's normal cell of origin found in the germinal centres of lymphoid tissue. By contrast, isogenic BL cell clones which have activated expression of all eight EBV latent proteins are resistant to the induction of apoptosis. The EBV latent proteins should therefore be seen not just as activators of B-cell proliferation but, perhaps more importantly, as mediators of enhanced B-cell survival.

Antigens, Differentiation, B-Lymphocyte↗

Epstein-Barr virus (EBV)-associated lymphoproliferative disease in the SCID mouse model: implications for the pathogenesis of EBV-positive lymphomas in man.

When human peripheral blood lymphocytes (PBLs) from Epstein-Barr virus (EBV)-seropositive donors are injected intraperitoneally into SCID mice, EBV+ B cell tumors develop within weeks. A preliminary report (Mosier, D. E., R. J. Gulizia, S. M. Baird, D. D. Richman, D. B. Wilson, R. I. Fox, and T. J. Kipps, 1989. Blood. 74(Suppl. 1):52a) has suggested that such tumors resemble the EBV-positive malignancy, Burkitt's lymphoma. The present work shows that generally the human (hu) PBL-SCID tumors are distinct from Burkitt's lymphoma and instead resemble lymphoblastoid cell lines (LCLs) generated by EBV-infection of normal B cells in vitro in terms of: (a) their cell surface phenotype, with expression of B cell activation antigens and adhesion molecules, (b) normal karyotype, and (c) viral phenotype, with expression of all the transformation-associated EBV latent proteins and, in a minority of cells, productive cycle antigens. Indeed, in vitro-transformed LCLs also grow when inoculated into SCID mice, the frequency of tumor outgrowth correlating with the in vitro growth phenotype of the LCL which is itself determined by the identity of the transforming virus (i.e., type 1 or type 2 EBV). Histologically the PBL-derived hu-SCID tumors resemble the EBV+ large cell lymphomas that develop in immuno-suppressed patients and, like the human tumors, often present at multiple sites as individual monoclonal or oligoclonal foci. The remarkable efficiency of tumor development in the hu-SCID model suggests that lymphomagenesis involves direct outgrowth of EBV-transformed B cells without requirement for secondary genetic changes, and that selection on the basis of cell growth rate alone is sufficient to explain the monoclonal/oligoclonal nature of tumor foci. EBV+ large cell lymphoma of the immunosuppressed may arise in a similar way.

Animals↗

The effects of ingesting polylactate or glucose polymer drinks during prolonged exercise.

Five trained, fasted male cyclists rode a cycle ergometer three times at 50% of VO2max for 180 min. Using a balanced order, double-blind procedure, subjects were given either a solution containing polylactate (PL: 80% polylactate, 20% sodium lactate, in 7% solution with water), glucose polymer (GP: multidextrin in 7% solution with water), or control (C: water sweetened with aspartame) 5 min before exercise and at 20-min intervals during exercise. Venous blood samples were taken at rest and at 20-min intervals during exercise. In general, PL and GP rendered similar results except that pH and bicarbonate (HCO3-) were higher in PL. There were no differences between treatments in perceived exertion, sodium, potassium, chloride, lactate, heart rate, oxygen consumption, rectal temperature, or selected skin temperatures. These data show that polylactate may help maintain blood glucose and enhance blood buffering capacity during prolonged exercise and could be a useful component in an athletic fluid replacement beverage.

Adult↗

General practitioners' detection of depression and dementia in elderly patients.

In a study of 11 general practitioners' detection of dementia and depression in 101 elderly patients it was found that general practitioners were more accurate in their detection of dementia than depression. The general practitioners did not identify 12 of the 15 patients assessed as depressed by a Diagnostic Interview for Depression, but their assessments of dementia corresponded quite well with the results of dementia tests. The general practitioners' knowledge of the symptoms and signs of dementia and depression was limited. If the patient talked to the general practitioner about feeling depressed, sad or irritable, the depression recognition rate increased.

Activities of Daily Living↗

The effects of shear stress on endothelial cell retention and function on expanded polytetrafluoroethylene.

We evaluated the adherence of indium 111-radiolabeled endothelial cells to fibronectin-treated expanded polytetrafluoroethylene surfaces exposed to high (437 s-1) vs low (218 s-1) shear and the influence of shear on prostacyclin production. Canine jugular vein factor VIII-positive endothelial cells in passages 3 through 6 were incubated with 111Indium-oxine, and labeled cells were seeded onto fibronectin-treated expanded polytetrafluoroethylene patches. Patches with confluent cells were exposed to shear in a Weissenberg rheogoniometer for intervals ranging up to 60 minutes. Percent endothelial cell retention was determined by gamma counting of patches and media and by histologic evaluation. Prostacyclin production (tritiated radioimmunoassay of 6-keto-prostaglandin F1 alpha) was assayed on perfusing media. Results showed no differences in 6-keto-prostaglandin F1 alpha production between shear rates or time periods. Endothelial cell retention did not differ between the shear rates. Rotational shear caused persistent cell loss over time in either high- or low-shear conditions. This persistent cell loss in response to steady rotational shear differs from that in response to identical rates of pulsatile linear shear in our laboratory where cell loss approached zero after 15 minutes.

Animals↗

Twins: a test of the equal environments assumption.

We asked a sample of 343 adult same-sex twin pairs a number of questions about the similarity of their social environment during childhood and early adolescence. A factor analysis of their responses indicated that their common environment was derived from two sources, one being similar treatment "imposed" upon them by their parents, the other being "elicited" by the twins' similar interests and behavior. Monozygotic (MZ) twins reported experiencing more similar "imposed" and "elicited" environments than dizygotic (DZ) twins. The extent of imposed similar treatment received during childhood and early adolescence was unrelated to either MZ or DZ twins' current behavioral similarity, as indicated by absolute intrapair differences in their Neuroticism, Anxiety, and Depression scores. Similar treatment imposed upon MZ twins on the basis of their zygosity alone is therefore not a threat to the validity of the twin method.

Adolescent↗