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Biomedical subjects

J P Mitchell

Publications and source records attributed to J P Mitchell.

At least 37 records · Page 2Linked to original sources

Food behaviors of southern rural community-living elderly.

OBJECTIVE: To examine how food behaviors and indicators of nutritional status of elderly living in rural communities might relate to age, race, income, medication use, activities of daily living and instrumental activities of daily living, living arrangements, and other lifestyle and health measures. DESIGN: In-home survey administered by trained interviewers. SETTING: Communities in rural North Carolina. PARTICIPANTS: A total of 2178 adults, aged 60 years and older, representing a 2% random stratified example of the region's elderly. MAIN OUTCOME MEASURES: Weight status described by body mass index, functional status as activities of daily living and instrumental activities of daily living, and self-reported food and health behaviors. RESULTS: Substantial diversity exists among households by age, race, residential location, and household size. Almost three fourths of respondents had seen a physician in the last 6 months. More than 33% of women and 28% of men were obese, but none reported having been prescribed a weight-loss diet. About 18% of the respondents were underweight. Weight was not related to income, perceptions of health, chronic disease, medication use, feelings of depression, instrumental activities of daily living, or exercise. Most (65%) ate three meals per day, and almost all were able to eat without assistance. Few drank much liquid or participated in structured exercise programs. Research is needed to determine the impact of weight status on the quality of life of elderly persons living in rural areas. CONCLUSIONS: Current literature descriptions of food behaviors and nutritional status of the elderly may not appropriately describe rural elderly. Attention should be given to the identification and treatment of malnutrition in the elderly.

Activities of Daily Living↗

The effects of quality and timing of venepuncture on markers of blood coagulation in healthy middle-aged men.

Effects of the quality and the time of venepuncture on factor VII coagulant activity (VIIc) and the concentrations of fibrinogen, prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FPA) were sought in 2665 men, of whom 2334 were re-examined after about one year. Venepunctures were categorised as satisfactory, not fully satisfactory or unsatisfactory according to pre-defined criteria. Neither the quality nor timing of the venepuncture influenced VIIc or fibrinogen concentration. However, at baseline and re-examination F1 + 2 and FPA were increased on average by about 9% and 45% respectively when venepunctures were not fully satisfactory, and by about 11% and 100% when unsatisfactory. Plasma collected after 1500 h had slightly but significantly lower levels of F1 + 2 and FPA than samples taken earlier, possibly due to circadian rhythm. The results emphasise the need for careful surveillance of the venepuncture procedure and the value of FPA when using F1 + 2 as a marker of risk of thrombosis.

Antigens↗

Microangiopathy of brain, retina, and inner ear.

Microangiopathy of brain, retina, and inner ear is a rare syndrome manifesting as arteriolar occlusions of the brain, retina, and inner ear, with resultant encephalopathy, visual, and hearing loss. Despite exhaustive laboratory examinations in these patients, no evidence of a systemic disease can be found. We treated and followed an adolescent with this disorder who initially presented with a branch retinal artery occlusion. A unique finding in this case was retinal vessel wall hyperfluorescence noted five days prior to retinal infarction. The patient developed recurrent branch artery occlusions, sensorineural hearing loss, and central nervous system infarctions despite anticoagulation and immunosuppressive treatment.

Adult↗

Coming to terms with advanced breast cancer: black women's narratives from eastern North Carolina.

This paper analyzes in-depth interviews with 26 black women who entered the medical system in rural North Carolina with advanced breast disease. In these narratives, women draw on multiple sources of knowledge in order to come to terms with the diagnosis of breast cancer--a biomedically-defined disease that they often refuse to acknowledge or accept. The analysis demonstrates how women relate the meaning of their individual episodes of illness to one or more of the following sources of knowledge: an indigenous model of health emphasizing balance in the blood, popular American notions about cancer, and particular biomedical conceptions about breast disease and its treatment. These narratives provide an important window into the processes involved when individuals attempt to adapt personal experience to pre-existing cultural models, modify such models in the light of new information, and confront conflicts in their own interpretations of the meaning of a single episode of illness.

Adult↗

Gibberellin (GA3) enhances cell wall invertase activity and mRNA levels in elongating dwarf pea (Pisum sativum) shoots.

The invertase (EC 3.2.1.26) purified from cell walls of dwarf pea stems to homogeneity has a molecular mass of 64 kilodaltons (kD). Poly(A)+RNA was isolated from shoots of dwarf pea plants, and a cDNA library was constructed using lambda gt11 as an expression vector. The expression cDNA library was screened with polyclonal antibodies against pea cell wall invertase. One invertase cDNA clone was characterized as a full-length cDNA with 1,863 base pairs. Compared with other known invertases, one homologous region in the amino acid sequence was found. The conserved motif, Asn-Asp-Pro-Asn-Gly, is located near the N-terminal end of invertase. Northern blot analysis showed that the amount of invertase mRNA (1.86 kb) was rapidly induced to a maximal level 4 h after GA3 treatment, then gradually decreased to the control level. The mRNA level at 4 h in GA3-treated peas was fivefold higher than that of the control group. The maximal increase in activity of pea cell wall invertase elicited by GA3 occcured at 8 h after GA3 treatment. This invertase isoform was shown immunocytochemically to be localized in the cell walls, where a 10-fold higher accumulation occurred in GA3-treated tissue compared with control tissue. This study indicates that the expression of the pea shoot cell-wall invertase gene could be regulated by GA3 at transcriptional and/or translational levels.

Amino Acid Sequence↗

The Stroke Prevention Patient Outcomes Research Team. Goals and methods.

BACKGROUND AND PURPOSE: The aim of the present study, based at Duke University and involving 14 other institutions, is to identify the most appropriate and cost-effective clinical strategies for prevention of ischemic (thrombotic or embolic) stroke in high-risk individuals and to design and test an intervention to disseminate this information to providers and the public. METHODS: The study uses (1) secondary data from literature review, Medicare claims, and population-based data from three epidemiological studies and (2) primary data generated in national physician and patient surveys and in demonstration trials. Phases I through III involve data collection and analysis using a decision/cost-effectiveness model and consensus development methods. Phase IV includes intervention in physicians' practice patterns. Data is collected by literature survey and abstraction, review of medical records, claims analysis, and patient and physician surveys. CONCLUSIONS: A structured decision model and a well-defined clinical focus provide a successful organization for a PORT on stroke prevention.

Cerebrovascular Disorders↗

Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization.

We performed a randomized, prospective trial to evaluate whether fluid management that emphasized diuresis and fluid restriction in patients with pulmonary edema could affect the development or resolution of extravascular lung water (EVLW), as well as time on mechanical ventilation and time in the intensive care unit (ICU), in critically ill patients requiring pulmonary artery catheterization (PAC). PAC was performed on 101 patients. A total of 52 patients were randomized to an EVLW management group using a protocol based on bedside indicator-dilution measurements of EVLW. The other 49 patients were randomized to a wedge pressure (WP) management group in whom fluid management decisions were guided by WP measurements. A total of 89 patients had pulmonary edema (defined as EVLW greater than 7 ml/kg ideal body weight). Except for a clinically unimportant difference in mean age, the two groups were entirely comparable at baseline. The study groups were managed differently, as evidenced by cumulative input-output of 2,239 +/- 3,695 ml (median = 1,600 ml) in the WP group versus 142 +/- 3,632 ml (median = 754 ml) in the EVLW group (p = 0.001). EVLW decreased significantly, and ventilator-days and ICU days were significantly shorter only in patients from the EVLW group. No clinically significant adverse effect occurred as a result of following the EVLW group algorithm. Thus, a lower positive fluid balance, especially in patients with pulmonary edema regardless of cause, is associated with reduced EVLW, ventilator-days, and ICU days.

Algorithms↗

Fluid balance during pulmonary edema. Is fluid gain a marker or a cause of poor outcome?

STUDY OBJECTIVE: To evaluate the importance of fluid balance and changes in extravascular lung water (EVLW) on survival in the ICU and short-term outcome in patients with pulmonary edema. DESIGN: Retrospective analysis of data (sorting by survival and "treatment received") from a recent randomized controlled trial of fluid restriction in this population. SETTING: Medical ICU of a university-affiliated, tertiary-care medical center. PATIENTS: Eighty-nine patients (from the previously mentioned study) requiring pulmonary artery catheterization with abnormally high EVLW (greater than 7 ml/kg). MEASUREMENTS AND RESULTS: When analyzed by survival, the survivors had no significant fluid gain or change in EVLW but decreased wedge pressure and body weight, compared to nonsurvivors. When analyzed by fluid balance, patients who gained less than 1 L of fluid by 36 hours into the study had a better rate of survival (74 percent) than the rest (50 percent; p less than 0.05). Also, the median duration of days on the ventilator, ICU days, and days of hospitalization was approximately half as long for each variable in the group with less than 1 L of fluid gain. Even accounting for baseline differences in the severity of illness, fluid balance was an independent predictor of survival (p less than 0.05). When analyzed by whether or not EVLW decreased by more than 15 percent between the first and last measurement, only patients with ARDS or sepsis had decreased days on the ventilator and ICU days. CONCLUSIONS: These data support the concept that positive fluid balance per se is at least partially responsible for poor outcome in patients with pulmonary edema and defend the strategy of attempting to achieve a negative fluid balance if tolerated hemodynamically.

Extravascular Lung Water↗

Site-specific phosphorylation of tyrosine hydroxylase after KCl depolarization and nerve growth factor treatment of PC12 cells.

The phosphorylation and activation of tyrosine hydroxylase was examined in PC12 cells following depolarization with KCl or treatment with nerve growth factor. Both treatments activate tyrosine hydroxylase (TH) and increase enzyme phosphorylation. Site-specific analysis of the tryptic phosphopeptides of TH isolated from [32P]phosphate-labeled PC12 cells demonstrated that the major phosphorylated peptide (termed "H25") did not contain any of the previously reported phosphorylation sites. Phosphoamino acid analysis of this peptide demonstrated that the phosphorylated residue was a serine. Synthetic tryptic peptides containing putative phosphorylation sites were prepared, and subjected to high performance liquid chromatography analysis and isoelectric focusing. The tryptic phosphopeptide containing serine 31 comigrated with the H25 peptide during both of these analytical techniques. The tryptic phosphopeptide produced by the phosphorylation of tyrosine hydroxylase by the recently discovered proline-directed protein kinase and the phosphorylated synthetic phosphopeptide TH2-12 are clearly separated from H25 by this analysis. We conclude that serine 31 is phosphorylated during KCl depolarization and nerve growth factor treatment of PC12 cells and that this phosphorylation is responsible for the activation of tyrosine hydroxylase. Since this site is not located in a sequence selective for any of the "classical" protein kinases, we suggest that a novel protein kinase may be responsible for the phosphorylation of this site. Since serine 31 has a proline residue on the carboxyl-terminal side, the possibility that this kinase may be related to the recently reported proline-directed protein kinase is discussed. Other sites that are also phosphorylated on TH during KCl depolarization include serine 19, which is known to be phosphorylated by calmodulin-dependent protein kinase II. A schematic model for the regulation of tyrosine hydroxylase activity by phosphorylation of the NH2-terminal regulatory domain is presented.

Adrenal Gland Neoplasms↗

Phosphorylation of synapsin I at a novel site by proline-directed protein kinase.

Previous studies identified synapsin I as a potential substrate for a newly discovered growth factor-sensitive, proline-directed protein kinase originally isolated from rat pheochromocytoma. The present study describes the site-specific phosphorylation of synapsin I by highly purified preparations of proline-directed protein kinase. The incorporation of [32P]phosphate into bovine brain synapsin I was dependent upon both the amount of kinase present and the time of incubation. The maximum stoichiometry of phosphorylation approached 1 mol of phosphate/mol of synapsin I protein. When analyzed by sodium dodecyl sulfate-gel electrophoresis and autoradiography, [32P]phosphate was found to be incorporated into both synapsin Ia and Ib. Phosphoamino acid analysis demonstrated that serine residues were phosphorylated exclusively. Digestion of phosphorylated synapsin I with trypsin followed by high performance liquid chromatography (HPLC) phosphopeptide analysis indicated that the tryptic peptide containing the major phosphorylation site eluted as a single peak at approximately 17% acetonitrile. The primary structure of this phosphopeptide, determined by gas-phase sequencing, was found to be Gln-Ser-Arg-Pro-Val-Ala-Gly-Gly-Pro-Gly-Ala-Pro-Pro-Ala-Thr-Arg-Pro-Pro- Ala-Ser-Pro-Ser-Pro-Gln-Arg. Sequential Edman degradation of this HPLC-purified tryptic phosphopeptide revealed that serine 20 of this peptide was the major phosphorylated residue. This phosphoacceptor site is immediately flanked by a carboxyl-terminal proline residue, an observation that further verifies the proline-directed nature of this protein kinase. The tryptic phosphopeptide corresponds exactly to a sequence in the collagenase-sensitive, proline-rich "tail" region of bovine synapsin I. This novel phosphorylation site is close to but distinct from phosphorylation sites 2 and 3, which are known to be phosphorylated by calcium/calmodulin-dependent protein kinase II and are considered to be of regulatory importance.

Amino Acid Sequence↗

Strain, social support, and mental health in rural elderly individuals.

This study examined the relationships among social support, life strain, and mental health in a sample of 210 rural elderly individuals. Life strain was operationalized as economic deprivation, illness disability, and ADL impairment. Demographic characteristics had little effect on mental health. Physical health status was highly predictive of life satisfaction and psychological distress among rural elderly individuals. Disability associated with chronic illness and ADL impairment was related to increased reports of symptoms of emotional and psychosomatic distress. Measures of social contacts and instrumental support exerted small to moderate effects on life satisfaction, psychosomatic distress, and emotional distress. Affective support moderated the effects of health-related strain on mental health.

Activities of Daily Living↗

Identification of a novel proline-directed serine/threonine protein kinase in rat pheochromocytoma.

During investigations of the regulation of tyrosine hydroxylase (TH) by protein phosphorylation, a novel protein kinase activity has been discovered in rat pheochromocytoma. Originally detected as a trace contaminant in preparations of highly purified TH, this novel kinase activity phosphorylated TH at serine 8 in the proline-rich amino-terminal region of the enzyme. This particular site is not phosphorylated by, nor is the amino acid sequence surrounding this site selective for, any of the classical (i.e. well characterized) protein kinases. In this report, we describe the identification, characterization, and partial purification of this novel protein kinase. By utilizing a synthetic peptide corresponding to the amino-terminal region of TH, a selective assay for this protein kinase was developed. The kinase activity utilized ATP and magnesium, although GTP could also be utilized as a phosphate donor. The kinase activity was found to co-purify with TH activity through ammonium sulfate precipitation and DEAE-cellulose chromatography and could be only partially resolved from TH by heparin-agarose affinity chromatography. Substantial kinase activity could be resolved from TH by phosphocellulose chromatography. The novel kinase migrates as a protein with a molecular mass of approximately 45 kDa on gel permeation chromatography as well as sucrose density gradient centrifugation. Studies of site specificity indicate that this Ser/Thr kinase activity appears to be directed by an adjacent (carboxyl-terminal) proline residue, exhibiting a minimal recognition sequence of -X-Ser/Thr-Pro-X-. In addition to TH, this proline-directed protein kinase will also phosphorylate synapsin I, histone H1, and glycogen synthase, suggesting that this kinase may have multiple substrates in vivo. Additional findings indicate that the activity of proline-directed protein kinase is increased transiently in PC12 pheochromocytoma cells following treatment with nerve growth factor. Distinctions between this novel kinase and other well characterized protein kinases can be made on the basis of phosphorylation site specificity, chromatographic behavior, and physical characteristics.

Adrenal Gland Neoplasms↗

Altered reactivity of the rat adrenal medulla.

Previous studies have suggested that experimental alterations in adrenomedullary reactivity, i.e., changes in catecholamine release in response to a standard dose of acetylcholine, may be partially accounted for by changes occurring at the level of the adrenal medulla itself, independent of both the central nervous system and the innervation of the adrenal gland. The present study was designed to investigate the morphology of adrenal chromaffin cells in rats subjected to chronic hypoglycemia induced by long acting insulin, and to assess this morphology in terms of associated changes in catecholamine content and release. Surgically isolated, perfused adrenal gland preparations were utilized to characterize the functional release of catecholamines from the adrenal medulla. Pretreatment with long acting insulin resulted in a selective depletion of epinephrine stores and acetylcholine-mediated epinephrine release, but did not appear to significantly affect either the levels or the release of norepinephrine. The biochemical effects of long acting insulin persisted for several days after termination of the treatment, exhibiting a gradual recovery over a period of approximately 5 days. Electron microscopic examination of the adrenal chromaffin cells revealed a progressive degranulation and vacuolization of numerous chromaffin cells followed by a compensatory biosynthetic response and a gradual recovery toward the morphology of control cells. The functional release of catecholamines from adrenal chromaffin cells was further examined in preparations of perfused adrenal slices. Acetylcholine-mediated catecholamine release was significantly decreased in slices of adrenal glands prepared from insulin treated rats when compared with that of control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗