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Biomedical subjects

S Jackson

Publications and source records attributed to S Jackson.

At least 199 records · Page 11Linked to original sources

Ontogenetic development of gut function, growth, and metabolism in a wild bird, the Red Jungle Fowl.

We measured the ontogeny of growth rate, food intake, metabolic rates, organ masses, and intestinal nutrient transporter and hydrolase activities in a wild bird for comparison with previous measurements of the same quantities in four domesticated or laboratory animals. Analysis of covariance with body mass as a covariate showed that body mass accounted for most of the age-related variation in all variables, but that age itself still had a significant effect on most variables. Among organs studied, the ceca exhibited the greatest mass increase with age. Energy intake and resting and basal metabolic rates increased with age, but digestive efficiency, cost of growth, and sustained metabolic scope were independent of age. Although intestinal brush-border glucose and proline uptakes and sucrase activity declined with age, the corresponding capacities increased with age because of compensating increases in intestinal mass. Intestinal passive permeability to glucose was undetectably low. Unlike the four domesticated animals studied to date, jungle fowl possess no intestinal reserve capacities (excesses of capacity over dietary nutrient intake). Cecal absorption may contribute significantly to glucose uptake capacity with increasing age.

Animal Nutritional Physiological Phenomena↗

Fatty acid oxidation in peripheral blood cells: characterization and use for the diagnosis of defects of fatty acid oxidation.

Disorders of mitochondrial fatty acid oxidation are increasingly recognized as an important group of inborn errors of metabolism that are associated with a significant, but easily preventable, morbidity and mortality in children. However, diagnosis is often delayed because there is no easily applied method that detects all defects. Therefore, we have characterized the acylcarnitine intermediates of fatty acid oxidation in peripheral blood cells from healthy control volunteers and patients with four different defects. After selective permeabilization with histone II AS, a novel permeabilizing agent, the cells were incubated with [U-14C]hexadecanoate and beta-oxidation flux and the acylcarnitine esters formed were measured. Blood cells from the control population produced large amounts of 3-hydroxyacylcarnitines and 2-enoylcarnitine esters, in addition to saturated acylcarnitine esters. This result is different from that found in other tissues (fibroblasts and muscle), where only saturated acylcarnitine esters could be detected. In blood cells from patients with defects of enzymes involved in long-chain fatty acid oxidation, flux was significantly reduced at 15 to 20% of control values (7.1 +/- 2.3 nmol C2 units formed per minute per International Unit of citrate synthase activity). There was a characteristic accumulation of acylcarnitines that was pathognomonic for the site of the defect. Thus, analysis of beta-oxidation intermediates from blood cells allows unequivocal identification of the four most common beta-oxidation defects.

Acylation↗

Dynamics of the interactions of histones H2A,H2B and H3,H4 with torsionally stressed DNA.

The interactions of histones H2A,H2B and H3,H4 with closed circular DNA maintained in either a positively or negatively coiled state have been studied. The interactions were assayed by measuring the rate at which negative stress was stored in the DNA by the histones and by the salt concentration sufficient to cause dissociation on sucrose gradients. Additional experiments were performed in which DNAs of substantially different molecular weights and opposite topological states were mixed with the histones in order to study histone mobility under varied conditions. This mobility was characterized by separating the complexes on sucrose gradients and by analyzing the DNA's topological state after topoisomerase I treatment. Histones H3,H4 were found to differ substantially from histones H2A,H2B with regard to the DNA topology with which they prefer to interact. The results are consistent with a model in which transcription-induced positive stress in advance of the RNA polymerase unfolds the nucleosome to facilitate the release of H2A,H2B. The data are also consistent with a model in which histones H3,H4 remain associated with the DNA during polymerase passage and serve as a nucleation site for the reassociation of H2A,H2B. The rapid production of transcription-induced negative stress in the wake of a polymerase would have substantial importance in facilitating the reassociation of histones H2A,H2B.

Biomechanical Phenomena↗

Investigating severe and fatal asthma.

BACKGROUND: Severe asthma continues to present a major therapeutic problem despite advances in our understanding of the disease. Innovative ideas for investigating the underlying causes and treatment of severe asthma are few, and many patients still become dependent on oral steroids. We describe two separate studies: first, a prospective investigation measuring the responses of persons with severe asthma to an allergen-free environment; second, a retrospective analysis of factors associated with eight fatalities and one near fatality caused by asthma exacerbations. METHODS: In the prospective study 17 persons with severe asthma were admitted to a hospital clinical research unit containing an allergen-free room for steroid dose reduction. Peak flow measurements, treatment requirements, and evidence of infection were followed up. In the retrospective study, the cases of nine patients who had been evaluated for asthma and who subsequently died during an asthma attack were reviewed; where possible allergen levels in their house dust and specific IgE antibodies to common indoor allergens were measured. RESULTS: Analysis of the patients in the prospective study revealed two categories of responses to steroid dose reduction: (1) asthmatic persons who either maintained or improved peak flow values on steroid reduction; these patients were predominantly allergic to indoor allergens; (2) asthmatic persons whose condition deteriorated; these patients were unable to tolerate reduction in steroid dose. The second group included persons with sensitization to fungal antigens who had asthmatic exacerbations in association with culture-documented fungal colonization. The retrospective study revealed that in five of the eight fatalities caused by asthma, exposure to a relevant allergen had occurred at home before death. CONCLUSION: Some steroid-dependent persons with severe asthma are allergic to inhalant allergens and may benefit from avoiding allergens. In some cases there is no evidence that antigen exposure from diet, inhalants, fungal infections, or sinusitis is relevant to their disease. However, persons with severe asthma include individuals infected with and sensitized to fungal antigens. The results suggest that cases of severe asthma should be investigated to identify treatable causes.

Adrenal Cortex Hormones↗

Escape from the antiproliferative effect of transforming growth factor-beta 1 in LLC-PK1 renal epithelial cells.

Transforming growth factor-beta 1 (TGF-beta 1) usually inhibits proliferation of epithelial cells. We find that LLC-PK1 renal tubular epithelial cells develop rapid in vitro resistance to the inhibitory effects of TGF-beta 1 and subsequently proliferate in response to TGF-beta 1. This unique response to TGF-beta 1 is not observed in another renal tubular epithelial cell line (MDCK cells). The proliferative response to TGF-beta 1 is additive to that produced by other growth factors. The proliferative response to TGF-beta 1 occurs despite an effect of TGF-beta 1 to suppress epidermal growth factor stimulated c-myc mRNA as determined by Northern analyses. These results suggest that LLC-PK1 cells develop rapid resistance to TGF-beta 1 inhibition of proliferation in vitro and that this resistance occurs despite continued suppression of c-myc mRNA.

Animals↗

Contrasting IgA and IgG neutralization capacities and responses to HIV type 1 gp120 V3 loop in HIV-infected individuals.

Quantitative analysis for HIV-1-specific antibodies present in IgA and IgG preparations purified from the serum of HIV-seropositive individuals indicated that the proportion of HIV-specific antibodies present within the IgG isotype was seven times greater than the proportion of IgA HIV antibodies present within the IgA isotype. Dilution of IgA HIV-specific antibodies by nonspecific IgA was observed in patients with elevated serum IgA concentrations, whereas proportions of IgG HIV antibodies rose with increases in concentrations of serum IgG. Although proportions of IgA HIV antibodies were not observed to correlate with the CD4 counts of the individuals from whom immunoglobulins were purified, a significant association between the numbers of such cells and proportion of HIV antibodies present in the IgG isotype was found. Equivalent amounts of IgG were also more effective than IgA at inhibiting HIV-1IIIB infection of a susceptible T cell line. This may be due to the presence of higher proportions of IgG antibodies directed toward non-V3 determinants because reactivity against an HIV-1IIIB V3 peptide was low and did not differ significantly between these isotopes. IgA antibodies reacting against a V3 peptide containing the HIV consensus sequence could be detected in the majority of IgA samples purified from infected individuals. Proportions of IgG consensus V3-specific antibodies within the purified IgG samples were, however, much higher. The presence of accompanying increases in serum IgG concentration and proportions of IgG HIV antibodies, higher proportions of both HIV- and consensus V3-specific antibodies within this isotype, and more effective neutralization by IgG suggests that an HIV-driven response is dominated by B cells committed to production of this immunoglobulin isotype. The observed low proportions of HIV antigen-specific IgA antibodies with dilution in many individuals by elevations in non-HIV-specific IgA suggests that IgA B cells may be more susceptible to factors that mediate the polyclonal activation believed to be responsible for many of the B cell disorders characteristic of HIV infection.

Acquired Immunodeficiency Syndrome↗

Intestinal mucosal immunoglobulins during human immunodeficiency virus type 1 infection.

In intestinal fluid samples from 39 human immunodeficiency virus type 1 (HIV-1)-infected patients, IgA and IgG levels were equivalent, whereas in 10 controls, IgA levels were significantly higher than those of IgG (P < .05). Intestinal IgA in patients contained predominantly monomeric IgA1, whereas IgA1 and IgA2 subclass levels in controls were nearly equivalent and primarily polymeric. The predominance of IgG and monomeric IgA1 in mucosal fluid samples from HIV-1-infected patients suggests exudation of serum immunoglobulins into the intestine. The decreased proportion of mucosal plasma cells producing IgA and IgA2 in the HIV-1-infected patients (P < .01) may also contribute to the abnormal intestinal immunoglobulin levels. Intestinal IgG reacted with most HIV-1 antigens, whereas specific IgA was present in only 10 of 17 patients and reacted with only envelope (gp120 and gp160) and, less often, core (p17 and p24) antigens. Aberrant mucosal antibody responses and decreased integrity of the mucosal barrier may contribute to the intestinal dysfunction and infections that characterize HIV-1 infection.

Diarrhea↗

Surgical patterns of venous drainage of the free forearm flap in head and neck reconstruction.

A retrospective review of 40 consecutive free forearm flaps used in head and neck reconstruction in our Head and Neck Service identified five different patterns of venous drainage. In type 1, the cephalic vein and two venae comitantes join into a larger median cubital vein, which itself splits into two sizable branches (n = 8, two anastomoses). In type 2, a median cubital vein drains both the cephalic vein and the two venae comitantes (n = 17, single anastomosis). In type 3, the cephalic vein and the confluence of two venae comitantes are drained separately (n = 7, two anastomoses). In type 4, the cephalic vein and each of two venae comitantes are anastomosed separately (n = 2, three separate anastomoses). In type 5, the cephalic vein and the larger of the two venae comitantes are drained separately (n = 6, two anastomoses). Understanding these possible venous drainage patterns substantially expedites the raising of the free forearm flap. The selection of patterns 1 and 2, when possible, with the large-caliber veins ensures the safety of the flap. Long vascular pedicles permit anastomoses to contralateral neck recipient vessels, obviating vein grafts, and permit safe full head and neck mobility.

Anastomosis, Surgical↗

Relationship between weakness and muscle wasting in rheumatoid arthritis.

OBJECTIVE: To relate weakness of grip to loss of forearm muscle bulk, hand joint deformity, and hand joint tenderness in patients with rheumatoid arthritis (RA). METHODS: Using anthropometric data we have estimated the anatomical cross-sectional area (CSA) of forearm muscles in 100 subjects with RA compared with 100 aged and sex-matched normal subjects. We also recorded hand joint tenderness using a modification of the Ritchie articular index, and a simple index of hand joint deformity. RESULTS: We found a significant reduction in anatomical CSA in RA (forearm CSA in normal subjects 29.7 cm2 and in RA 25.9 cm2; p = 0.002). In simple linear regression we found that 46.3% of the variation in grip strength in normal subjects was explained by variation in muscle CSA; in RA this figure decreased to 33.4%. Adding terms for joint deformity and pain in a multiple regression model improved the amount of variation explained to 37.9%. CONCLUSIONS: Although there is significant muscle wasting in RA, it is likely that reduction in strength is also attributable to joint deformity and pain leading to inhibition of grip directly and, indirectly, by arthrogenous muscle inhibition. Doubts remain about the quality of muscle in RA.

Adult↗

Very long-chain acyl coenzyme A dehydrogenase deficiency presenting with exercise-induced myoglobinuria.

A young man presented with recurrent episodes of muscle pain and myoglobinuria after prolonged exercise or fasting. Studies on isolated muscle mitochondria showed slow flux through beta-oxidation and the presence of only saturated long-chain acyl coenzyme A (acyl-CoA) esters. These results strongly suggested a defect in the dehydrogenation of long-chain acyl-CoA esters that we confirmed by measurement of enzyme activity in muscle and platelet mitochondrial fractions and fibroblast homogenates. In all tissues studied from the patient, the enzyme activity was approximately 10% of control values with acyl-CoA esters from C16-C22 as substrates. We investigated the intramitochondrial location of the deficient acyl-CoA dehydrogenase by subfractionation of platelet mitochondria and, in contrast to the short-chain and medium-chain enzymes, which were localized in the soluble fraction, the majority of the acyl-CoA dehydrogenase activity with long-chain substrates was in the membrane fraction. These studies indicate that in humans, the predominant enzyme catalyzing the dehydrogenation of long-chain acyl-CoA esters is membrane-bound and that deficiency of this enzyme is a cause of muscle pain and rhabdomyolysis.

Acyl-CoA Dehydrogenase, Long-Chain↗

Management ... working day of a health services manager. North Staffordshire Hospital.

Physiotherapy needs to change to be relevant and appropriate to the delivery of health care in the future: departments in acute units will become smaller as therapists' expertise is required in the community. Sue Jackson, Physiotherapy Manager, North Staffordshire Hospital, describes the first steps in this culture change--and other professional and human resource issues.

Hospital Administrators↗

Immunological studies of IgA nephropathy in blacks reveal elevations of serum IgA2 as well as IgA1.

Although IgA nephropathy (IgAN) is recognized worldwide as the most common primary glomerulonephritis, the prevalence of this disease among American blacks is strikingly low despite the frequency of other renal disorders. We have previously described the clinical features of 27 black patients enrolled in a multicentre IgAN database; in this paper we report several immunological parameters of the disease in this population. Quantification of serum immunoglobulins revealed significantly higher concentrations of total IgA, IgA1 and IgA2 (P = 0.0001, 0.002 and 0.005 respectively) in the patients, but no significant increases in IgG or IgM. Examination of immunoglobulin synthesis by peripheral blood lymphocytes indicated relatively few differences in the secretion of immunoglobulins by patients compared to healthy American blacks. The spontaneous production of total IgA, IgA1, and IgA2 in patients was depressed compared to the control subjects (P = 0.02, 0.04, 0.03,), yet the ratio of IgA1:IgA2 was normal. Stimulation with pokeweed mitogen enhanced secretion of immunoglobulin in both subject groups. However, a significantly greater IgA1:IgA2 ratio was noted in the patients (P = 0.002). Circulating immune complexes containing C3 and IgA as well as C3 and IgM were elevated in the patients (P = 0.0006, 0.0003 and 0.02, respectively). These immunological aberrancies did not correlate with clinical manifestations of disease. These data suggest the immune abnormalities of black IgAN patients are similar to, but not identical with, those of white patients.

Adult↗