Further modification of the dual-hemostat port closure technique.
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Hemostasis, Surgical↗
Biomedical subjects
J Horner
Publications and source records attributed to J Horner.
Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development.
XRCC4 is a non-homologous end-joining protein employed in DNA double strand break repair and in V(D)J recombination. In mice, XRCC4-deficiency causes a pleiotropic phenotype, which includes embryonic lethality and massive neuronal apoptosis. When DNA damage is not repaired, activation of the cell cycle checkpoint protein p53 can lead to apoptosis. Here we show that p53-deficiency rescues several aspects of the XRCC4-deficient phenotype, including embryonic lethality, neuronal apoptosis, and impaired cellular proliferation. However, there was no significant rescue of impaired V(D)J recombination or lymphocyte development. Although p53-deficiency allowed postnatal survival of XRCC4-deficient mice, they routinely succumbed to pro-B-cell lymphomas which had chromosomal translocations linking amplified c-myc oncogene and IgH locus sequences. Moreover, even XRCC4-deficient embryonic fibroblasts exhibited marked genomic instability including chromosomal translocations. Our findings support a crucial role for the non-homologous end-joining pathway as a caretaker of the mammalian genome, a role required both for normal development and for suppression of tumours.
Animals↗
DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway.
DNA ligase IV (LIG4) is a nonhomologous end-joining (NHEJ) protein used for V(D)J recombination and DNA repair. In mice, Lig4 deficiency causes embryonic lethality, massive neuronal apoptosis, arrested lymphogenesis, and various cellular defects. Herein, we assess potential roles in this phenotype for INK4a/ARF and p53, two proteins implicated in apoptosis and senescence. INK4a/ARF deficiency rescued proliferation/senescence defects of Lig4-deficient fibroblasts but not other phenotypic aspects. In contrast, p53 deficiency rescued embryonic lethality, neuronal apoptosis, and fibroblast proliferation/senescence defects but not lymphocyte development or radiosensitivity. Young Lig4/p53 double null mice routinely died from pro-B lymphomas. Thus, in the context of Lig4 deficiency, embryonic lethality and neuronal apoptosis likely result from a p53-dependent response to unrepaired DNA damage, and neuronal apoptosis and lymphocyte developmental defects can be mechanistically dissociated.
Animals↗
Role of mood in outcome of biofeedback assisted relaxation therapy in insulin dependent diabetes mellitus.
Stressful life events and negative mood have been associated with elevated blood glucose and poor self-care in individuals with diabetes. The purpose of this controlled study was to determine the effect of mood state, specifically depression, anxiety, and daily hassles on the outcome of biofeedback assisted relaxation in insulin dependent diabetes mellitus. Eighteen subjects completed the study, nine in biofeedback assisted relaxation and nine in the control group. There were no significant group differences in blood glucose between those receiving biofeedback assisted relaxation and the subjects continuing usual care. Five of the nine experimental subjects and one of the nine control subjects were identified as succeeders according to an arbitrary criterion. Treatment failures were more depressed, more anxious, and took longer to complete the protocol than succeeders. Statistically significant correlations were found between high scores on inventories measuring depression, anxiety, and hassles intensity and higher blood glucose levels and smaller changes in blood glucose as a result of treatment. It is suggested that mood has an important impact on the response to biofeedback assisted relaxation. Further research is necessary to determine whether assessment of anxiety and depression followed by appropriate treatment where necessary should precede biofeedback assisted relaxation in insulin dependent diabetes.
Adult↗
Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo.
This study examines in vivo the role and functional interrelationships of components regulating exit from the G1 resting phase into the DNA synthetic (S) phase of the cell cycle. Our approach made use of several key experimental attributes of the developing mouse lens, namely its strong dependence on pRb in maintenance of the postmitotic state, the down-regulation of cyclins D and E and up-regulation of the p57(KIP2) inhibitor in the postmitotic lens fiber cell compartment, and the ability to target transgene expression to this compartment. These attributes provide an ideal in vivo context in which to examine the consequences of forced cyclin expression and/or of loss of p57(KIP2) inhibitor function in a cellular compartment that permits an accurate quantitation of cellular proliferation and apoptosis rates in situ. Here, we demonstrate that, despite substantial overlap in cyclin transgene expression levels, D-type and E cyclins exhibited clear functional differences in promoting entry into S phase. In general, forced expression of the D-type cyclins was more efficient than cyclin E in driving lens fiber cells into S phase. In the case of cyclins D1 and D2, ectopic proliferation required their enhanced nuclear localization through CDK4 coexpression. High nuclear levels of cyclin E and CDK2, while not sufficient to promote efficient exit from G1, did act synergistically with ectopic cyclin D/CDK4. The functional differences between D-type and E cyclins was most evident in the p57(KIP2)-deficient lens wherein cyclin D overexpression induced a rate of proliferation equivalent to that of the pRb null lens, while overexpression of cyclin E did not increase the rate of proliferation over that induced by the loss of p57(KIP2) function. These in vivo analyses provide strong biological support for the prevailing view that the antecedent actions of cyclin D/CDK4 act cooperatively with cyclin E/CDK2 and antagonistically with p57(KIP2) to regulate the G1/S transition in a cell type highly dependent upon pRb.
Animals↗
Laparoscopic cholecystectomy, bile duct injury and the British and Irish surgeon.
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Bile Ducts↗
Carbon monoxide: the invisible killer.
Carbon monoxide (CO) is a colourless, odourless and tasteless gas. It is emitted when carbon containing compounds are incompletely combusted. This paper reports on concentrations of CO in the environment in relation to anthropogenic emission sources and assesses the extent of the health hazard from this common air pollutant. It includes the results of CO monitoring in a variety of locations in south west London. The conclusion is that indoor emission sources present a greater and more insidious health risk than do outdoor emission sources. Methods for reducing the dangers it poses are briefly summarised.
Air Pollutants↗
Laparoscopic cholecystectomy, bile duct injury and the British and Irish surgeon.
Laparoscopic cholecystectomy continues to attract controversy with regard to a perceived higher incidence of bile duct injury than in the open procedure. One possible cause for this is the trend away from intraoperative cholangiography previously considered an essential part of the open procedure. Under the auspices of The Association of Surgeons of Great Britain and Ireland, a questionnaire was sent to all its consultant fellows asking for details about their individual experience of the most serious injury, bile duct resection. In all, 1100 questionnaires were sent; 362 (33%) replies were returned. Of those who replied, 300 performed laparoscopic cholecystectomy as part of their practice. The experience of the respondents was divided into three groups; 19 surgeons had performed < 50 laparoscopic cholecystectomies, 53 between 50 and 100 and 228 had performed over 100. Ninety-five (32%) never performed intraoperative cholangiography, 167 (56%) on a selective basis and 38 (12%) routinely. In all, 58 bile duct resection injuries were reported by 48 surgeons. Of the bile duct resection injuries reported, 49 of 58 (85%) occurred when an intraoperative cholangiogram was not performed. These figures suggest that if the incidence of bile duct resection injury is to be decreased in laparoscopic cholecystectomy, the use of intraoperative cholangiography has an integral role to play.
Bile Ducts↗
Incidence and nature of bile duct injuries following laparoscopic cholecystectomy: an audit of 5913 cases.
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Bile Ducts↗
HRSA's strategies to combat family violence.
This paper discusses the efforts of the Health Resources and Services Administration (HRSA) to work with a broad constituency to combat and ultimately prevent family violence. In partnership with states and communities, HRSA implements programs to strengthen health care infrastructure, support direct community-based service delivery, and educate health care providers. Soliciting and incorporating community input are critical steps in designing innovative training approaches to deal with pressing health concerns, such as the efforts of family violence in a community. This type of collaboration is evident in HRSA's programs such as the Area Health Education Centers, the Geriatric Education Centers, and the AIDS Education and Training Centers. Health care delivery systems and special health interventions must respond to the far-reaching effects of family violence. HRSA is devising a comprehensive strategy to guide program development in violence intervention. This strategy would build on successful models of education, prevention, and service delivery, as well as identification of critical areas for collaboration between community activists, researchers, epidemiologists, health care providers, policymakers, academicians, survivors, philanthropists, representatives from state and local government, and the faith community.
Domestic Violence↗
Expression and activity of L-Myc in normal mouse development.
To determine the role of L-Myc in normal mammalian development and its functional relationship to other members of the Myc family, we determined the normal patterns of L-myc gene expression in the developing mouse by RNA in situ hybridization and assessed the phenotypic impact of L-Myc deficiency produced through standard gene targeting methodology. L-myc transcripts were detected in the developing kidney and lung as well as in both the proliferative and the differentiative zones of the brain and neural tube. Despite significant expression of L-myc in developing mouse tissue, homozygous null L-myc mice were found to be viable, reproductively competent, and represented in expected frequencies from heterozygous matings. A detailed histological survey of embryonic and adult tissues, characterization of an embryonic neuronal marker, and measurement of cellular proliferation in situ did not reveal any congenital abnormalities. The lack of an apparent phenotype associated with L-Myc deficiency indicates that L-Myc is dispensable for gross morphological development and argues against a unique role for L-Myc in early central nervous system development as had been previously suggested. Although overlapping expression patterns among myc family members raise the possibility of complementation of L-Myc deficiency by other Myc oncoproteins, compensatory changes in the levels of c- and/or N-myc transcripts were not detected in homozygous null L-myc mice.
Animals↗
Tegument changes of Schistosoma japonicum and Schistosoma mansoni in mice treated with artemether.
AIM: To study the effect of artemether (Art) on the tegument of schistosomes. METHODS: Mice infected with S japonicum cercariae for 7 and 35 d, or with S mansoni cercariae for 49 d were treated intragastrically with Art 200-300 mg.kg-1.d-1 for 2 d. Schistosomes were collected in groups of 2 mice at various intervals after medication for scanning electron microscopic observation. RESULTS: The tegumental changes induced by Art appeared to be similar in S japonicum and S mansoni: swelling and fusion of tegumental surfaces, vesicle formation and collapse of discoid-like sensory structures. In S japonicum the emergence of tegumental alterations was earlier in 7-d-old schistosomulae than that in 35-d-old adult worms. CONCLUSION: Art injured the teguments of S japonicum and S mansoni.
Animals↗
Contrasting roles for c-Myc and L-Myc in the regulation of cellular growth and differentiation in vivo.
Although myc family genes are differentially expressed during development, their expression frequently overlaps, suggesting that they may serve both distinct and common biological functions. In addition, alterations in their expression occur at major developmental transitions in many cell lineages. For example, during mouse lens maturation, the growth arrest and differentiation of epithelial cells into lens fiber cells is associated with a decrease in L- and c-myc expression and a reciprocal rise in N-myc levels. To determine whether the down-regulation of L- and c-myc are required for mitotic arrest and/or completion of differentiation and whether these genes have distinct or similar activities in the same cell type, we have studied the consequences of forced L- and c-myc expression in the lens fiber cell compartment using the alpha A-crystallin promoter in transgenic mice (alpha A/L-myc and alpha A/c-myc mice). With respect to morphological and molecular differentiation, alpha A/L-myc lenses were characterized by a severely disorganized lens fiber cell compartment and a significant decrease in the expression of a late-stage differentiation marker (MIP26); in contrast, differentiation appeared to be unaffected in alpha A/c-myc mice. Furthermore, an analysis of proliferation indicated that while alpha A/L-myc fiber cells withdrew properly from the cell cycle, inappropriate cell cycle progression occurred in the lens fiber cell compartment of alpha A/c-myc mice. These observations indicate that continued late-stage expression of L-myc affected differentiation processes directly, rather than indirectly through deregulated growth control, whereas constitutive c-myc expression inhibited proliferative arrest, but did not appear to disturb differentiation. As a direct corollary, our data indicate that L-Myc and c-Myc are involved in distinct physiological processes in the same cell type.
Amino Acid Sequence↗
Interfacial morphology and strength of bonds made to superficial versus deep dentin.
PURPOSE: To evaluate the interfacial morphology (SEM) of two bonding systems to superficial and deep dentin using a reverse-sandwich technique, coupled with measurement of micro-tensile bond strengths (MTBS). MATERIALS AND METHODDS: Superficial and deep dentin disks were prepared from the same tooth in freshly-extracted human third molars. All-Bond 2 (total etch versus no etch) or Imperva Bond (total etch versus no etch) were applied to superficial versus deep dentin surfaces and the two disks were bonded together into a reverse-sandwich configuration. RESULTS: SEM revealed that All-Bond 2 and Imperva Bond applied under total etch conditions formed thicker resin-infiltrated layers (4-8 micrometers) on deep dentin than on superficial dentin (2-4 micrometers), and that All-Bond 2 and Imperva Bond applied to unetched dentin formed very thin resin-infiltrated layers (less than 0.5 micrometers) on both dentin substrates. MTBS of All-Bond 2 and Imperva Bond were more than 20 MPa irrespective of dentin depth and were not significantly different. Without acid etching, the MTBS of both systems to deep dentin was significantly lower than to superficial dentin. These results suggested that for the total-etch systems, dentin depth affected the thickness of the resin-infiltrated layer, but the thickness of the resin-infiltrated layer had no significant relationship with MBTS. The present data also indicated that the acid-etch technique could prevent the decrease of bond strength seen in deep dentin in the absence of etching.
Acid Etching, Dental↗
Swallowing in Alzheimer's disease.
Using a prospective case series design, we examined the incidence of oropharyngeal swallowing abnormalities in 25 patients with moderate or severe Alzheimer's disease by videofluoroscopy. Aspiration occurred in 6 of 25 (28.6%). Only four patients showed unequivocally normal performance. Exploratory statistical analyses showed that swallowing abnormalities associated significantly with duration of dementia, eating dependency, and abnormal oral praxis. We observed a trend toward a higher incidence of aspiration in patients with more severe dementia. We conclude that oropharyngeal swallowing abnormalities, including aspiration, are more prevalent in patients with Alzheimer's disease than in normal elderly individuals.
Aged↗
Evaluation of the effects of diagnostic radiation on titanium dental implant osseointegration in the micropig.
The effect that diagnostic radiation may have on peri-implant supporting alveolar tissues is not well understood. Fifty-four (54) titanium dental implants were inserted into the posterior mandible of nine micropigs. At implant placement surgery, 18 implants were exposed to either 2 (diagnostic) or 10 (excessive) doses of diagnostic radiation; the remaining 36 implants served as controls. Fourteen weeks after implant placement, standardized clinical radiographs were taken, pigs were euthanized, and implants with supporting alveolar tissues were prepared and examined by light and scanning electron microscopy (SEM). Ninety-seven sections were evaluated by SEM for morphometric and morphologic analyses. The mean percent of implant length in contact with bone was 47% for the controls and 53% for the implants receiving radiation. Five implants were lost during the initial healing phase and four implants were clinically mobile at time of euthanasia, giving a success rate of 83% (45/54). Correlative light microscopy of peri-implant supporting tissues revealed no distinct differences between the microvasculature of controls versus implants exposed to radiation. Standardized clinical radiographs revealed crestal saucerization in both control and radiated implants. This study revealed no statistically significant difference for the percent of implant length in contact with alveolar bone for controls or implants exposed to 2 or 10 doses of diagnostic radiation at implant placement time.
Alveolar Process↗
Swallowing, speech, and brainstem auditory-evoked potentials in spasmodic torticollis.
To explore the controversial "brainstem theory" of spasmodic torticollis, eight consecutively referred patients were examined. Three independent examinations were conducted on the same day: a videofluoroscopic barium swallowing examination, an instrumental speech examination, and a brainstem auditory-evoked potential (BAEP) analysis. Swallowing was normal in two patients; speech physiology, in five; and BAEPs, in all. Normal BAEPs refute the brainstem theory, while abnormalities of speech and swallowing temper this conclusion. Several alternative explanations are proposed.
Adult↗