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Biomedical subjects

C Morris

Publications and source records attributed to C Morris.

At least 127 records · Page 7Linked to original sources

Clinical and laboratory features of patients with loiasis (Loa loa filariasis) in the U.K.

To assess differences between Africans and expatriates, we reviewed records of 100 patients with loiasis presenting to The Hospital for Tropical Diseases, London. Fifty-one were black Africans, and 49 were white expatriates. A history of Calabar swellings was more common amongst expatriates (P = 0.0001, OR 8.1), whilst eyeworm was reported more frequently in Africans (P = 0.0038, OR 4.2). Higher eosinophil levels (P < 0.0001) and filarial antibody levels, whether measured by immunofluorescence (P = 0.047) or ELISA (P < 0.0001) were present in the expatriates. Africans were more likely to have microfilaraemia (P < 0.0025, OR 7.3), and among microfilaraemic patients, Africans had denser microfilaraemia (P = 0.012). The sensitivity of microfilaremia as a screening test for loiasis was 75% in Africans and 29% in expatriates. The sensitivities of filarial antibody tests in Africans and expatriates were 81% and 100% for IFAT, and 28% and 93% for ELISA. Following treatment, 63% of patients were considered cured, 25% were lost to follow-up and 12% had a documented relapse. The differences between the two groups of patients could be caused by differences in the chronicity of loiasis, but other explanations are also discussed.

Adolescent↗

The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9.

The t(7;11)(p15;p15) translocation is a recurrent chromosomal abnormality associated primarily with acute myeloid leukaemia (FAB M2 and M4). We present here the molecular definition of this translocation. On chromosome 7 positional cloning revealed the consistent rearrangement of the HOXA9 gene, which encodes a class I homeodomain protein potentially involved in myeloid differentiation. On chromosome 11 the translocation targets the human homologue of NUP98, a member of the GLFG nucleoporin family. Chimaeric messages spliced over the breakpoint fuse the GLFG repeat domains of NUP98 in-frame to the HOXA9 homeobox. The predicted NUP98-HOXA9 fusion protein may promote leukaemogenesis through inhibition of HOXA9-mediated terminal differentiation and/or aberrant nucleocytoplasmic transport.

Amino Acid Sequence↗

Improved quality of life in patients with generalized cardiovascular metabolic disease on a prepared diet.

Current dietary recommendation for cardiovascular disease risk reduction and recommended dietary allowances (RDAs) were used to develop a nutritionally complete prepackaged prepared meal plan specifically designed to reduce the risk of cardiovascular disease. In the current study we tested patient acceptance of the diet as defined by measures of quality of life. In a randomized, parallel-design, multicenter clinical trial, 77 persons with hypertension, diabetes mellitus, dyslipidemia, or a combination of two or more of these conditions were recruited and randomly assigned to either a prepared meal plan (n = 39) or a comparable self-selected diet (n = 38) for 10 wk. The prepared meal plan met both the RDAs for all essential micronutrients and the dietary recommendations of national health organizations for macronutrients, cholesterol, sodium, and fiber. The prescribed self-selected diet was matched for macronutrients. Quality of life, as measured by a battery of instruments, was the major endpoint. Individuals consuming the prepared meal plan had significant improvements in mental health (P < 0.01), general perceived health (P < 0.005), daily activities (P < 0.05), work performance (P < 0.005), affect (P < 0.01), and nutritional health perceptions (P < 0.001), and reductions in nutrition hassles based on a standardized questionnaire (P < 0.001). The self-selected-diet group had significant improvements in nutritional health perceptions (P < 0.001) and affect (P < 0.001). There were significant improvements in weight (P < 0.001), blood pressure (P < 0.001), cholesterol (P < 0.002), low-density lipoproteins (P < 0.001), glucose (P < 0.014), and glycated hemoglobin (Hb A(1c) (P < 0.004) that were comparable in both groups. In summary, this study shows that a nutritionally complete diet, whether prepackaged or self-selected, improves multiple risk factors for cardiovascular disease. The prepackaged prepared meal plan had the added benefit of a greater improvement in quality of life.

Blood Glucose↗

A walking program for nursing home residents: effects on walk endurance, physical activity, mobility, and quality of life.

OBJECTIVES: To determine the effects of a 12-week walking program on walk endurance capacity, physical activity level, mobility, and quality of life in ambulatory nursing home residents who had been identified as having low physical activity levels and low walk endurance capacities. To determine the effects of 12 versus 22 weeks of walk training on walk endurance capacity, physical activity level, mobility, and quality of life in ambulatory nursing home residents. DESIGN: Experiment 1: Residents of one nursing home campus were assigned to the walking program, and residents of a second campus were assigned to the social visit control group. Outcome measures were taken before and after 12 weeks. Experiment 2: Pretest/posttest with outcome measures taken before and, again, after 12 and 22 weeks of walking. SETTING: Two campuses of the Jewish Homes for the Aging in the Los Angeles area. PARTICIPANTS: Experiment 1: Nineteen of 22 residents in the walking group completed the walking program, and 12 of 15 residents in the control group completed the study. Experiment 2: Thirty of 41 residents (from the two nursing homes) completed the 22-week walking program. INTERVENTION: Experiment 1: The walking program involved each resident walking with research staff at his/her self-selected walking pace, 5 days per week for 12 weeks, for a maximum of 30 minutes per day; while the control group had weekly individual social visits, which lasted 30 minutes, from a research assistant. Experiment 2: All residents, those in both the walking and the control group, were offered the opportunity to complete 22 weeks of walking. MAIN OUTCOME MEASURES: Maximal walk endurance capacity, the resident's maximum walk time performed in a single day of walking (distance and speed also were measured); physical activity level based on time-sampled observations and physical activity monitors; mobility as measured with the Timed-Up-and-Go test, left handgrip strength, and Tinetti's Mobility Assessment; and quality of life as assessed with the Geriatric Depression Scale (a bodily pain scale) and the Dartmouth Primary Care Cooperative Information Project (COOP) physical work chart. RESULTS: Experiment 1: The walking group significantly improved their maximal walk endurance time by 77% and distance by 92%, with no significant change in walk speed; however, the control group showed no significant changes in these variables. There were no significant group by time interactions on measures of physical activity, mobility, and quality of life. Experiment 2: No further significant changes were found from 12 to 22 weeks in walk endurance capacity, physical activity, mobility, or quality of life. CONCLUSION: Twelve weeks of daily walking at a self-selected walking pace by ambulatory nursing home residents produced significant improvements in walk endurance capacity. No other significant changes were noted in physical activity level, mobility, or quality of life in either group after the intervention. Also, there were no side effects, such as increases in falls or cardiovascular complications, due to the walking intervention. Lengthening the walking program to 22 weeks produced no further significant changes in any outcome measures.

Activities of Daily Living↗

Muscarinic activation inhibits T-type Ca2+ current in hen granulosa cells.

The effect of the muscarinic agonist carbachol on Ca2+ currents in hen granulosa cells isolated from the largest ovarian follicle was studied. The major Ca2+ current observed using the perforated patch technique with a recording solution containing 10 mM Ca2+, but no Na+ or K+, exhibited characteristics typical of T-type Ca2+ current: maximal amplitude at -20 mV, rapid inactivation (half-time of 42 +/- 3 msec at -20 mV), inhibition by 100 microM Ni2+, and insensitivity to the dihydropyridine Ca2+ channel antagonist, nifedipine. In all cell studied, carbachol (0.5 mM) caused an inhibition of this current (elicited by depolarizing pulses from -70 to -20 mV) to an average maximal decrease of 90 +/- 2% below basal values. In some 50% of the cells, the Ca2+ current also partially recovered during the 10-min exposure to the muscarinic agonist. These effects were prevented by the muscarinic antagonist atropine (1 microM). To test whether this inhibition was due to increases in intracellular free Ca2+ concentrations ([Ca2+]i), [Ca2+]i was simultaneously measured in fura-2-loaded cells. For cells incubated in normal solution, [Ca2+]i was 0.15 +/- 0.02 microM, but increased to 0.25 +/- 0.6 microM in cells exposed to the recording solution. Under these conditions, carbachol failed to produce the expected [Ca2+]i transients, but, rather, caused a small decrease (8 +/- 2%) in basal [Ca2+]i attributable to its diminution of Ca2+ current. Thus, the results demonstrated an important muscarinic inhibition of the T-type Ca2+ current not related to [Ca2+]i fluctuations. They indicate, on the other hand, that [Ca2+]i can strongly modulate carbachol-induced mobilization of Ca2+ from the intracellular stores.

Animals↗

Keratin expression in pilosebaceous epithelia in truncal skin of acne patients.

This study compared the pattern of keratin expression in pilosebaceous follicles in uninvolved trunk skin of acne patients, comedones, and normal control skin by immunohistochemistry, using both immunofluorescent (IF) and immunoperoxidase (IP) techniques. The shape, size and gross morphology of truncal follicles varied greatly. There was no difference in keratin expression between normal skin and uninvolved skin of patients with acne. The upper part of the pilosebaceous duct expressed keratins K1, K5, K10 and K14, whereas the lower duct expressed keratins K5, K6, K14, K16, K17 and K19. The sebaceous gland showed considerable heterogeneity in keratin expression, with some lobules expressing keratins K1, K5, K7, K10, K14 and K17. The comedone wall showed a pattern of keratin expression similar to that of the upper follicle, except that there was, in addition, expression of keratins K6 and K16 suprabasally, and panepithelial expression of K17 in the comedone wall. IF techniques were found to be less sensitive than the IP method in the detection of individual keratins, but the use of multiple antibodies and many different transverse and longitudinal sections of follicles permitted full conclusions to be made. The increased expression of keratins K6, K16 and K17 in the comedone wall is likely to represent a secondary effect of increased cell turnover due to the primary underlying mechanism of comedogenesis, which is as yet unknown.

Acne Vulgaris↗

Spatial organization of ABR and CRK genes on human chromosome band 17p13.3.

Deletion of part or all of chromosome 17p is among the most frequent chromosome abnormalities in human cancer. We show that the CRK and ABR genes are close to a marker on chromosome 17p13.3, D17S34, which is frequently deleted in different tumours, and demonstrate that CRK is centromeric to ABR. CRK and ABR may be involved in cancer themselves, or otherwise may function as points of reference for further experiments to clone genes from chromosome 17p which may play a role in cancer.

Chromosome Banding↗

Bone marrow transplantation in a young child with sickle cell anemia.

Bone marrow transplantation (BMT) is the only curative therapy available for hemoglobinopathies. BMT was performed on a young child with sickle cell anemia (SCA) after approximately 9 months of transfusion therapy following her initial stroke. The patient received a matched sibling donor (sickle trait) BMT. The conditioning regimen consisted of busulfan 4 mg/kg/day x 4, cyclophosphamide 50 mg/kg/day x 4. Graft vs. host disease prophylaxis was daily cyclosporine for 6 months. There were no significant complications during BMT. Engraftment occurred on day +17 and the patient was transfusion independent since day +45. Pre-BMT cerebral arteriography showed multiple stenotic cerebral vessels and a moya-moya pattern. Perfusion MRI demonstrated reduced capillary perfusion. Approximately 170 days after BMT the patient experienced episodes of transient left-sided weakness and speech problems. Neuroimaging revealed progression of large vessel pathology by angiography despite significant improvement in cortical perfusion (MR perfusion scan). Molecular analysis by PCR and DNA fingerprinting confirmed absence of mixed mosaicism. Rheologic evaluation showed normal corrected bulk viscosity. It is possible that progression of large vessel pathology and return of clinical symptoms in the face of normal rheologic parameters may be due to worsening of the already damaged cerebral vessels by the BMT conditioning regimen. Further evaluations of patients with SCA undergoing BMT after a stroke are needed to answer this question.

Anemia, Sickle Cell↗

Fitting Weibull duration models with random effects.

Duration time models often should include correlated failure times, due to clustered data. These random effects hierarchical models sometimes are called "frailty models" when used for survival analyses. The data analyzed here involve such correlations because patient level outcomes (the times until graft failure following kidney transplantation) are observed, but patients are clustered in different transplant centers. We describe fitting such models by combining two kinds of software, one for parametric survival regression models, and the other for doing Poisson regression in a hierarchical setting. The latter is implemented by using PRIMM (Poisson Regression and Interactive Multilevel Modeling) methods and software (Christiansen & Morris, 1994a). An illustrative example for profiling data is included with k = 11 kidney transplant centers and N = 412 patients.

Graft Survival↗

Cochlear effects of indacrinone are not altered by penicillin.

Indacrinone is a loop diuretic structurally related to ethacrynic acid. Indacrinone is a racemic mixture. Previous studies have shown that the (-) enantiomer caused reduction of endocochlear potential (EP) and elevation of compound action potential (CAP) threshold (Rybak and Whitworth, 1987a). It has been demonstrated that organic acids such as penicillin, probenecid and sodium salicylate prevent the reduction of EP normally observed after furosemide administration (Rybak et al., 1992a). The present study was designed to determine whether penicillin pretreatment could prevent changes in EP and CAP threshold in (-)-indacrinone treated chinchillas. Adult chinchillas were anesthetized with ketamine and pentobarbital. A microelectrode was advanced into the scala media using the round window approach, and CAP responses to clicks were measured. One group was treated with (-)-indacrinone 100 mg/kg via the jugular vein. A second group of animals received penicillin 50 mg/kg i.v. thirty minutes before (-)-indacrinone. The mean EP change in the indacrinone-treated animals was 38.38 +/- 19.32 millivolts (mv). The reduction of EP in the group receiving penicillin was 24.43 +/- 20.74 mv (P > 0.09). The mean CAP threshold changes in animals receiving indacrinone was 20 +/- 14.14 dB whereas those pretreated with penicillin showed a threshold shift of 21.43 +/- 20.35 dB (P > 0.05). These findings are consistent with previous studies which showed that the effect of ethacrynic acid on the EP and CAP was not changed by the pretreatment with penicillin (Rybak et al., 1990).

Action Potentials↗

Dacarbazine and interferon-alpha 2a in advanced malignant melanoma: high response rate and prolongation of response duration occur in different patient subpopulations.

Fifty-three evaluable patients with metastatic malignant melanoma were enrolled in a phase II prospective study designed to assess the response rate, time to progression and survival after dacarbazine (DTIC) and interferon-alpha 2a (IFN-alpha 2a) treatment in patients with local metastatic disease compared with patients with distant metastases. Patients received intravenous DTIC from day 1 at a dosage of 400-500 mg/m2, repeated every 21 days (in the case of good tolerance--25 patients--the dose was increased to 600-800 mg/m2) combined with subcutaneous IFN-alpha 2a (9 x 10(6) U three times/week, increased in the case of good tolerance to 15 x 10(6) U three times/week). Forty-two patients with distant metastases were compared with 11 patients who had local metastatic disease. Three complete (6%) and six partial (11%) responses were seen, with an overall response rate of 17% (95% confidence interval 8-29). Patients with local metastases had a higher response rate (50%) compared with patients with distant metastases (visceral involvement, mediastinal and para-aortic lymph node metastases) (10%; p = 0.01). The median overall survival was 4.5 months. The progression-free interval for responders with distant metastases was significantly longer (11 months), than for responders with local metastases (4.5 months) (p = 0.004). These results may suggest that the combination treatment DTIC/IFN-alpha has a greater benefit in terms of longer progression-free interval in responders with distant metastases.

Adult↗

Antibody responses to Four Corners hantavirus infections in the deer mouse (Peromyscus maniculatus): identification of an immunodominant region of the viral nucleocapsid protein.

Antibody responses to Four Corners hantavirus (FCV) infections in the deer mouse (Peromyscus maniculatus) were characterized by using FCV nucleocapsid protein (N), glycoprotein 1 (G1), and glycoprotein 2 (G2) recombinant polypeptides in Western immunoblot assays. Strong immunoglobulin G reactivities to FCV N were observed among FCV-infected wild P. maniculatus mice (n = 34) and in laboratory-infected P. maniculatus mice (n = 11). No immunoglobulin G antibody reactivities to FCV G1 or G2 linear determinants were detected. The strongest N responses were mapped to an amino-proximal segment between amino acids 17 and 59 (QLVTARQKLKDAERAVELDPDDVNKSTLQSRRAAVSALETKLG). FCV N antibodies cross-reacted with recombinant N proteins encoded by Puumala, Seoul, and Hantaan viruses.

Amino Acid Sequence↗

Regulation of the cross-bridge transition from a weakly to strongly bound state in skinned rabbit muscle fibers.

The regulation of cross-bridge transition from weakly attached to force-bearing states was studied at 10 degrees C in skinned muscle fibers by measuring the rate of force development after a quick release-restretch cycle (ktr), the rate of force decline (kPi) after photogeneration of Pi from caged Pi, and stiffness in the presence and absence of an inhibitor of strong cross-bridge formation, 2,3-butanedione monoxime (BDM). Both BDM and Pi suppressed force more than stiffness. However, reduction of Ca2+ suppressed force and stiffness in a parallel fashion. Both ktr and kPi were reversibly reduced (by 30-35%) in 3 mM BDM, but both were increased by increasing Pi concentration. Reduction of Ca2+ concentration to match the force seen in 3 mM BDM had no effect on kPi but decreased ktr by 85%. These results are inconsistent with cross-bridge models undergoing the transition from a weakly bound to a force-generating state in a single step but are consistent with a model having two steps, one of which is controlled by pCa.

Actins↗

Pore properties of Lymnaea stagnalis neuron stretch-activated K+ channels

In many neurons, variations in membrane excitability are determined by a resting K+ conductance whose magnitude is modulated via neurotransmitters. The S-channel in Aplysia californica mechanosensory neurons is such a conductance, but it has also been shown to be a stretch-activated K+ channel. In this, it resembles stretch-activated K+ channels common to all molluscan neurons. Comparable channels are widespread, having been reported in molluscan and insect muscle and various vertebrate cells. The pore properties of the S-channel and similar stretch-activated K+ channels have received only sporadic attention. Here we examine, at the single-channel level, the permeation characteristics of a stretch-activated K+ channel from neurons of the mollusc Lymnaea stagnalis. Michaelis&shy;Menten constants (Km) for the conductance, obtained separately for inward (28 mmol l-1) and outward (91 mmol l-1) K+ currents, suggest that the channel presents to the external medium, where [K+] is lower, a higher-affinity site than it presents to the cytoplasmic medium. This may help to ensure that influx is not diffusion-limited at potentials near the resting potential, i.e. near the K+ equilibrium constant. Anomalous mole fraction behavior, observed when the ratio of permeant ion (K+ and Rb+) was varied, indicated that the stretch-activated K+ channel is a multi-ion pore. The ion selectivity sequence determined using reversal potentials under bi-ionic conditions was Cs+>K+>Rb+>NH4+>Na+>Li+, and using relative conductance in symmetrical solutions, the sequence was Tl+=K+>Rb+>NH4+>>Na+=Li+=Cs+. Extreme variations in extracellular pH from 4.7 to 11.4 had no effect on stretch-activated K+ channel conductance, whereas normal concentrations of extracellular Mg2+ reduced inward K+ current. Intracellular, but not extracellular, Ba2+ produced a slow, open channel block with an IC50 of 140&plusmn;80 &micro;mol l-1. These pore properties are compared with those of other stretch-activated K+ channels and of K+ channels in general. In spite of a greater than half order of magnitude difference in the cytoplasmic [K+] in marine (Aplysia californica) and freshwater (Lymnaea stagnalis) molluscs, the conductances of stretch-activated K+ channels from the two groups are very similar.

Journal Article↗

Choice matters: enrollees' views of their health plans.

Enrollees' views of their health plans and physicians are important measures of the performance of the health care system. The Commonwealth Fund's 1994 survey of 3,000 adults in fee-for-service and managed care organizations documents enrollees' experiences with choosing a plan and satisfaction with that plan. Fee-for-service enrollees were more satisfied with their plan's access to and quality of care; managed care enrollees were more satisfied with their plan's cost, paperwork, and coverage of preventive care. The survey also found a high rate of involuntary plan changing, limited choice of physicians, and low levels of satisfaction among low-income managed care enrollees.

Adolescent↗

Health insurance: the size and shape of the problem.

Assessment of experiences with health care will continue to be important given the rapid changes in the health care system and retreat from broad national attention on health reform. This paper reports on the findings of the 1993 Kaiser/Commonwealth Survey of Americans and their health insurance. The survey findings highlight the chronic problem of uninsurance as well as concerns among those with insurance, including the worry that benefits will be reduced or become unaffordable. Limited choice of health plans and providers and having to join a managed care plan are further concerns. These findings suggest that many Americans' needs remain unaddressed, but they will have to be considered as the health care system is restructured.

Consumer Behavior↗

Distribution of nicotinic receptors in the human hippocampus and thalamus.

Neuronal nicotinic acetylcholine receptors consist of different subunits, alpha and beta, with different subtype arrangement corresponding to distinct pharmacological and functional properties. The expression of alpha 3, alpha 7 and beta 2 mRNA in the human brain was studied by in situ hybridization and compared to [3H]nicotine, [3H]cytisine and [125I]alpha-bungarotoxin binding in contiguous sections. The beta 2 probe showed a strong hybridization signal in the granular layer of the dentate gyrus and in the CA2/CA3 region of the hippocampus and in the insular cortex, and a signal of lower intensity in the subicular complex and entorhinal cortex. The alpha 3 probe showed strong hybridization in the dorsomedial, lateral posterior, ventroposteromedial and reticular nuclei of the thalamus, and a weak signal in the hippocampal region and in the entorhinal, insular and cingular cortex. The amount of alpha 7 mRNA was high at the level of the dentate granular layer and the CA2/CA3 region of the hippocampus, in the caudate nucleus and in the pulvinar and ventroposterolateral nuclei of the thalamus. [3H]Nicotine and [3H]cytisine binding appeared to be identical in anatomical distribution and relative intensity. It was high in the thalamic nuclei, the putamen and in the hippocampal formation in the subicular complex and the stratum lacunosum moleculare. The level of [125I]alpha-bungarotoxin binding was particularly high in the hippocampus and in the pyramidal cells of the CA1 region, but was relatively low in the subicular complex. Our data indicate that in the human brain nicotinic receptor subtypes have discrete distributions, which are in part different from those of other species.

Adult↗