Simultaneous aortic aneurysm repair and colonic surgery.
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Aged↗
Biomedical subjects
J F Kelly
Publications and source records attributed to J F Kelly.
Child care and employment in relation to infants' disabilities and risk factors.
The impact of disability- and risk-related characteristics of 166 infants on their mothers' employment and child-care characteristics and decisions was investigated. Mothers' employment plans and child-care decisions were affected by their children's special needs (chronic health problems; use of adaptive equipment; total risks; diagnosis; and mental, motor, and adaptive functioning). Child-care characteristics were related most consistently to the children's diagnoses. Infants diagnosed with Down syndrome compared with those whose developmental delays were of unknown origin entered child care earlier and were more likely to be in centers and to be receiving lower quality care.
Adult↗
The effect of depression on return to drinking: a prospective study.
BACKGROUND: The effect of depression on return to drinking among individuals with alcohol dependence is controversial. From February 1, 1993, to April 15, 1996, we consecutively recruited 40 women and 61 men hospitalized for alcohol dependence and followed them up monthly for 1 year to assess the effect of depression on drinking outcomes. METHODS: We conducted structured interviews during hospitalization and monthly following discharge for 1 year to determine whether depression at treatment entry affected the likelihood of return to drinking and whether this effect differed between sexes. Using survival analysis, we examined the effect of depressive symptoms and a diagnosis of current major depression at treatment entry on times to first drink and relapse during follow-up. RESULTS: A diagnosis of current major depression at the time of hospitalization was associated with shorter times to first drink (hazard ratio, 2.03; 95% confidence interval [CI], 1.28-3.21; P=.003) and relapse (hazard ratio, 2.12; 95% CI, 1.32-3.39; P=.002). There was no significant difference between women and men in this effect. Depressive symptoms as measured by the Beck Depression Inventory did not predict time to first drink or relapse in women or men. CONCLUSIONS: A diagnosis of current major depression at entry into inpatient treatment for alcohol dependence predicted shorter times to first drink and relapse in women and men. Our results differ from earlier reports that men and women differ in the effect of depression on return to drinking.
Adult↗
The role of peroxisomes in aging.
Reactive oxygen species and alterations in membrane lipid homeostasis are thought to be important events in aging process and aging-related degenerative diseases. The peroxisome is a small cellular organelle involved in both oxygen and lipid metabolism, and defects in peroxisomal function are associated with major, and often fatal, changes at the neurological level during human development. Recent reports of aging-related changes in peroxisomal function raised the hypothesis that peroxisomes may also have a significant role in the aging process and aging-related degenerative diseases. This review presents the current data on changes in peroxisomal function during aging and discusses the implications of these changes for health.
Aging↗
Differential effect of aging on cholesterol modulation of carbachol-stimulated low-K(m) GTPase in striatal synaptosomes.
Previous research has suggested that age-related decline in physiological functions may be the result of substantial alterations in membrane molecular structure. The purpose of the present experiments was to elucidate the role of cholesterol domains in the age-related decline in receptor-G-protein interactions in striatal synaptosomes. We observed a significant age-related deficit in muscarinic cholinergic stimulated Low-Km GTPase activity and its age-related susceptibility to cholesterol treatment in range of 10(-10)-10(-5) M. Treatment of synaptosomes from old rats with cholesterol in range of 10(-8)-10(-6) M restored the Low-Km GTPase activity up to the level seen in young animals and reached a maximum at 10(-7) M. In synaptosomes from young rats, however, cholesterol treatment did not have any effect on striatal Low-Km GTPase activity. We observed significant alterations in the membrane lipid composition of striatal synaptosomes as a function of age. Our results suggested a significant interaction of age and cholesterol treatment on physical properties of striatal synaptosomes. Thus, the present results of experiments in vitro support our previous results of experiments in vivo and suggested an interaction of cholesterol domains with muscarinic-cholinergic receptor G-protein alpha subunit coupling/uncoupling through regulation of physical properties of striatal synaptosomes.
Aging↗
Early British surgical instruments.
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History, Ancient↗
Endothelial cell vehicles for delivery of cytotoxic genes as a gene therapy approach for carcinoma of the ovary.
Human umbilical vein endothelial cells (HUVECs) were evaluated for utility as a vector to achieve a bystander effect and killing of ovarian carcinoma cell lines. After demonstrating that HUVECs could be transduced with the reporter gene LacZ encoded by an adenoviral vector, appropriate cell killing of the AdCMVHSV-TK-transduced HUVECs was exhibited after treatment with 20 microM ganciclovir. Mixing experiments were then performed to determine whether the transduced HUVECs would demonstrate a bystander effect with the ovarian cancer cell lines. When 50% AdCMVHSV-TK-transduced HUVECs were mixed with untransduced ovarian cancer cells, > 70% of all cells were killed. Finally, s.c. and i.p. injections of herpes simplex-thymidine kinase-expressing HUVECs and SKOV3ip1 tumor cells were performed to evaluate the effects of HUVECs in in vivo models. These studies showed a decrease in tumor growth s.c. as well as a statistically significant survival prolongation (P < 0.05) in the i.p. model. These findings suggest that endothelial cells may be used as a vehicle for the delivery of cytotoxicity (bystander effect) in molecular chemotherapy.
Animals↗
4-Hydroxynonenal, an aldehydic product of lipid peroxidation, impairs signal transduction associated with muscarinic acetylcholine and metabotropic glutamate receptors: possible action on G alpha(q/11).
Considerable data indicate that oxidative stress and membrane lipid peroxidation contribute to neuronal degeneration in an array of age-related neurodegenerative disorders. In contrast, the impact of subtoxic levels of membrane lipid peroxidation on neuronal function is largely unknown. We now report that 4-hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, disrupts coupling of muscarinic cholinergic receptors and metabotropic glutamate receptors to phospholipase C-linked GTP-binding proteins in cultured rat cerebrocortical neurons. At subtoxic concentrations, HNE markedly inhibited GTPase activity, inositol phosphate release, and elevation of intracellular calcium levels induced by carbachol (muscarinic agonist) and (RS)-3,5-dihydroxyphenyl glycine (metabotropic glutamate receptor agonist). Maximal impairment of agonist-induced responses occurred within 30 min of exposure to HNE. Other aldehydes, including malondialdehyde, had little effect on agonist-induced responses. Antioxidants that suppress lipid peroxidation did not prevent impairment of agonist-induced responses by HNE, whereas glutathione, which is known to bind and detoxify HNE, did prevent impairment of agonist-induced responses. HNE itself did not induce oxidative stress. Immunoprecipitation-western blot analysis using an antibody to HNE-protein conjugates showed that HNE can bind to G alpha(q/11). HNE also significantly suppressed inositol phosphate release induced by aluminum fluoride. Collectively, our data suggest that HNE plays a role in altering receptor-G protein coupling in neurons under conditions of oxidative stress that may occur both normally, and before cell degeneration and death in pathological settings.
Aldehydes↗
Amyloid beta-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons.
Cholinergic pathways serve important functions in learning and memory processes, and deficits in cholinergic transmission occur in Alzheimer disease (AD). A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C, resulting in the liberation of inositol trisphosphate and Ca2+ release from intracellular stores. We now report that amyloid beta-peptide (Abeta), which forms plaques in the brain in AD, impairs muscarinic receptor activation of G proteins in cultured rat cortical neurons. Exposure of rodent fetal cortical neurons to Abeta25-35 and Abeta1-40 resulted in a concentration and time-dependent attenuation of carbachol-induced GTPase activity without affecting muscarinic receptor ligand binding parameters. Downstream events in the signal transduction cascade were similarly attenuated by Abeta. Carbachol-induced accumulation of inositol phosphates (IP, IP2, IP3, and IP4) was decreased and calcium imaging studies revealed that carbachol-induced release of calcium was severely impaired in neurons pretreated with Abeta. Muscarinic cholinergic signal transduction was disrupted with subtoxic levels of exposure to AP. The effects of Abeta on carbachol-induced GTPase activity and calcium release were attenuated by antioxidants, implicating free radicals in the mechanism whereby Abeta induced uncoupling of muscarinic receptors. These data demonstrate that Abeta disrupts muscarinic receptor coupling to G proteins that mediate induction of phosphoinositide accumulation and calcium release, findings that implicate Abeta in the impairment of cholinergic transmission that occurs in AD.
Amyloid beta-Peptides↗
Alzheimer's disease amyloid beta peptide 25-35 is localized in the membrane hydrocarbon core: x-ray diffraction analysis.
Alzheimer's disease (AD) neuropathology is characterized by neuritic plaques composed primarily of amyloid beta peptide (A beta). An elevation in A beta in the cerebral cortex has been implicated in the pathophysiology of AD but its mechanism of action is unknown. The addition of A beta protein to neuronal cell cultures produces changes in the activity of various membrane proteins, including ion channels and receptors, potentially as a result of intercalating into the membrane bilayer. In this study, the interactions of the A beta fragment 25-35 [A beta(25-35)] with liposomes were directly examined by small angle x-ray diffraction approaches. One-dimensional electron density profiles generated from the diffraction data demonstrated that the addition of A beta(25-35) produced a discrete increase in electron density 0-12 A from the center of the lipid bilayer. Under these conditions, the membrane concentration of A beta(25-35) was 860-fold higher than in the aqueous buffer. These findings indicate that this peptide is highly lipophilic and inserts into the membrane hydrocarbon core. Following the intercalation of A beta(25-35) to this location in the membrane, the protein fragment may interact with regulatory membrane proteins.
Amino Acid Sequence↗
Development of electrophoretic conditions for the characterization of protein glycoforms by capillary electrophoresis-electrospray mass spectrometry.
A capillary electrophoresis (CE) method using acidic buffers and capillaries coated with Polybrene, a cationic polymer has been developed for the separation of glycoproteins and glycopeptides. Electrophoretic conditions have been optimized to provide resolution of individual glycoforms observed for different glycoprotein preparations. These conditions were found to be entirely compatible with the operation of electrospray mass spectrometry (ESMS), which facilitated the assignments of possible carbohydrate compositions of glycopeptides arising from digests of glycoproteins. By using operating conditions enhanced the formation of oxonium fragment ions prior to mass spectral analysis, selective identification of glycopeptides was achieved for complex samples such as those from proteolytic digests or chemical cleavages. Examples of applications are presented for ribonuclease B, ovalbumin, horseradish peroxidase, and a lectin from Erithrina corallodendron using both CE-ESMS and CE with ultraviolet detection (CE-UV).
Carbohydrate Conformation↗
Age-related impairment in striatal muscarinic cholinergic signal transduction is associated with reduced membrane bilayer width measured by small angle X-ray diffraction.
In order to determine whether age-related changes in neuronal membrane structure contribute to previously reported changes in muscarinic cholinergic signal transduction, striata from 3, 13 and 23 month old F344 male rats were examined for both carbachol-stimulated low Km GTPase activity and membrane one-dimensional electron density profile using small angle X-ray diffraction. Increasing age was associated with both a reduction in stimulated GTPase activity and a decrease in membrane bilayer width. These findings suggest the possibility that fundamental membrane structural changes may contribute to alterations in signal transduction seen with aging.
Aging↗
Partial restoration of impaired alpha 1-adrenergic responsiveness in parotid cells of aged rats by S-adenosylmethionine treatment.
The age related decrease in alpha 1-adrenergic stimulated inositol 1, 4, 5 trisphosphate (IP3) production in parotid cells of aged rats can be partially restored by treatment with S-adenosylmethionine (SAM). This effect is completely blocked by S-adenosyl homocysteine (SAH) and occurs in association with an increase in the conversion of phosphatidylethanolamine to phosphatidylcholine and a decrease in membrane viscosity. In contrast, SAM treatment actually inhibits stimulated IP3 production in cells of young rats. The membrane viscosity of these cells is lower than that of those from aged rats. Although conversion of phosphatidylethanolamine to phosphatidylcholine is enhanced, no further decrease in membrane viscosity is elicited in young cell preparations. These findings suggest that age changes in the membrane environment may result in impaired alpha 1-adrenergic signal transduction and that such alterations may be at least partially reversible by SAM treatment.
Adrenergic alpha-1 Receptor Agonists↗
Dissociation of striatal GTPase and dopamine release responses to muscarinic cholinergic agonists in F344 rats: influence of age and dietary manipulation.
There is evidence that dietary lipids and age both influence neuronal membrane composition and receptor G protein-linked signal transduction, but very little information is available on the interaction between these two factors. To investigate this, we obtained striata from 2, 12, and 22-month-old male F344 rats who were fed either a high-cholesterol, high-saturated fat or low-fat diet for 1 month. The striata were assayed for muscarinic agonist-stimulated low-Km GTPase activity using 10(-3) M carbachol and 10(-5) M oxotremorine and for KCl-evoked dopamine release enhancement by 10(-5) M oxotremorine. Membrane cholesterol and phospholipid content and phospholipid class composition were also determined. Mature animals showed significant but divergent changes in GTPase activity and dopamine release for high-cholesterol and low-fat diets: GTPase activity decreased, whereas dopamine release increased in these groups. Alterations in GTPase activity but not in dopamine release were inversely correlated with the cholesterol/phospholipid molar ratio. Old control animals showed reductions in both GTPase activity and oxotremorine-enhanced dopamine release compared with young animals. Whereas none of the experimental diets affected GTPase activity in old animals, the low-fat diet produced a marked decrease in dopamine release. In contrast to mature and old groups, young rats showed no significant change in either GTPase or dopamine release, suggesting a relative "resistance" to such dietary lipid modulation. The observed dissociation in GTPase and dopamine release responses to diet may reflect differing effects of these diets on discrete membrane lipid domains that preferentially influence different signal transduction components. The substantial age-related differences in striatal membrane response to dietary lipid modulation may represent the effects of underlying age differences in membrane lipid metabolism, structure, and/or dynamics. Our findings support the work of other groups that have shown that brain membranes are susceptible to modification by exogenous lipids. They also suggest the need for a more systematic examination of the influence of age on the response to other types of dietary lipid changes.
Aging↗
Rapid and sensitive gas chromatographic determination of estazolam.
The triazolobenzodiazepine estazolam can be quantitated by gas chromatography with electron-capture detection. After addition of a suitable internal standard, plasma samples are extracted into toluene-isoamyl alcohol or benzene-isoamyl alcohol. The organic extract is separated, evaporated to dryness, reconstituted, and chromatographed using a 50:50 methyl-phenyl column (SP-2250). The sensitivity limit is approximately 1 ng of estazolam in a 1-ml sample. The method is suitable for clinical or experimental pharmacokinetic studies.
Animals↗
Synchronous aortic and gastrointestinal surgery.
The synchronous performance of aortic and gastrointestinal surgery may hold an increased risk of aortic graft infection. The experience of one surgeon who performed 32 such synchronous operations over a period of 11 years is reviewed. No graft infection occurred and it is concluded that such combined operations may be safer to perform than staged surgery in elderly patients.
Aged↗
Readmissions to a geriatric medical unit: is prevention possible?
Of the 622 patients admitted to a geriatric medical unit during the period November 1985 to October 1986, 211 (33.9%) had been discharged from hospital within the previous year. Of these, 117 (55.5%) had previously been admitted to the geriatric medical unit (18.8% of all admissions). The reasons for readmission were deterioration of existing disease (47.4%), new medical events (33.2%), poor management of previous discharge (9.5%), and social problems (5.7%). Age was not a significant factor influencing readmission. Readmission was judged preventable by better management of the previous admission and discharge in only 33 cases (15.6% of readmissions). A prospective study of the patients discharged in the same year revealed that 19.3% were readmitted in the following year, and of these readmissions 2.3% were considered to be preventable. There was no difference in medical causes for readmission in the two years. A significant number of the patients readmitted in both years studied was categorized as "high dependency". The figures suggest that although unplanned readmission is common, it is generally not preventable by better management of the previous admission, and often reflects a highly dependent and medically frail group of patients, in whom early intervention with readmission is appropriate.
Aged↗
A survey of oral and maxillofacial surgeons concerning their knowledge, beliefs, attitudes, and behavior relative to parameters of care.
In December 1990, a survey was sent to 1,296 randomly selected members of the American Association of Oral and Maxillofacial Surgeons (AAOMS) to determine their previous experience with standards and criteria of care, their type of practice, the educational methods that influence their professional decisions, and their attitudes about the development and use of parameters of care. A 55.7% response was obtained. This article reports the results of this survey. The average age of responding surgeons was 45 years and they had been in practice an average of 15 years. The majority were in private practice, had hospital staff privileges, worked between 31 and 55 hours per week, spent 90% of their working week in direct patient care, and devoted an average of 9.16 hours per month to professional affairs outside of their practice. Forty-two percent (42%) of the practitioners were in solo practice, whereas 50% practiced in groups. Surgeons concentrated 65% of their patient care time on dentoalveolar surgery and a significant number planned increases in practice activity in implant, orthognathic, and temporomandibular joint surgery. They learned new clinical skills in various ways, there being a difference between the most convenient and effective methods of learning. A majority of surgeons had been involved with quality assurance activities in the past 5 years. They were predominantly favorable to parameters now and when they first learned about them, but few thought they had a clear understanding about how parameters of care would be used.(ABSTRACT TRUNCATED AT 250 WORDS)
Dental Implantation, Endosseous↗