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Biomedical subjects

S A Barnes

Publications and source records attributed to S A Barnes.

12 recordsLinked to original sources

Relationship between muscle sympathetic nerve activity and systemic hemodynamics during nitric oxide synthase inhibition in humans.

Large interindividual differences exist in resting sympathetic nerve activity (SNA) among normotensive humans with similar arterial pressure (AP). We recently showed inverse relationships of resting SNA with cardiac output (CO) and vascular adrenergic responsiveness that appear to balance the influence of differences in SNA on blood pressure. In the present study, we tested whether nitric oxide (NO)-mediated vasodilation has a role in this balance by evaluating hemodynamic responses to systemic NO synthase (NOS) inhibition in individuals with low and high resting muscle SNA (MSNA). We measured MSNA via peroneal microneurography, CO via acetylene uptake and AP directly, at baseline and during increasing systemic doses of the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). Baseline MSNA ranged from 9 to 38 bursts/min (13 to 68 bursts/100 heartbeats). L-NMMA caused dose-dependent increases in AP and total peripheral resistance and reflex decreases in CO and MSNA. Increases in AP with L-NMMA were greater in individuals with high baseline MSNA (PANOVA<0.05). For example, after 8.5 mg/kg of L-NMMA, in the low MSNA subgroup (n=6, 28+/-4 bursts/100 heartbeats), AP increased 9+/-1 mmHg, whereas in the high-MSNA subgroup (n=6, 58+/-3 bursts/100 heartbeats), AP increased 15+/-2 mmHg (P<0.01). The high-MSNA subgroup had lower baseline CO and smaller decreases in CO with L-NMMA, but changes in total peripheral resistance were not different between groups. We conclude that differences in CO among individuals with varying sympathetic traffic have important hemodynamic implications during disruption of NO-mediated vasodilation.

Adult↗

Manipulating photosynthesis.

The levels of individual photosynthetic proteins can be independently decreased by the Agrobacterium-mediated transformation of plants with antisense RNA constructs. Protocols for the introduction of such constructs into Agrobacterium, the Agrobacterium-mediated transformation of tobacco leaf disks, and the screening and analysis of the transgenic plants produced are described.

Agrobacterium tumefaciens↗

fhy1 defines a branch point in phytochrome A signal transduction pathways for gene expression.

Physiological analysis of the fhy1 mutant of Arabidopsis has led to the proposal that the mutant is deficient in a downstream component of the phytochrome A signal transduction pathway. To define this lesion at the molecular level, we have examined the expression of a range of phytochrome-regulated genes in fhy1. In far-red light, the regulation of genes such as CHS and CHI is blocked in fhy1, whereas the induction of CAB and NR genes is affected minimally. In contrast, the induction of all genes tested is blocked in a phytochrome A-deficient mutant, confirming that gene expression in far-red light is regulated solely by phytochrome A. Thus, fhy1 defines a branch point in phytochrome A signal transduction pathways for gene expression. Contrary to the general opinion that responses to continuous red light are mediated by phytochrome B and other photostable phytochromes, we have shown also that red light-induction of CHS is mediated almost entirely by phytochrome A. Furthermore, phytochrome A-mediated induction of CHS by red light is blocked in fhy1. The induction of CHS by blue light, however, is normal in fhy1, suggesting that although FHY1 is a component of the phytochrome A signaling pathway, it is not a component of the blue-light signaling pathway for CHS expression.

Acyltransferases↗

Far-red light blocks greening of Arabidopsis seedlings via a phytochrome A-mediated change in plastid development.

We have characterized a far-red-light response that induces a novel pathway for plastid development in Arabidopsis seedlings. This response results in the inability of cotyledons to green upon subsequent white light illumination, and the response is suppressed by exogenous sucrose. Studies with mutants showed that this far-red block of greening is phytochrome A dependent and requires an intact downstream signaling pathway in which FHY1 and FHY3 may be components but in which HY5 is not. This highlights a previously undefined branchpoint in the phytochrome signaling pathway. Ultrastructural analysis showed that the far-red block correlates with both the failure of plastids to accumulate prolamellar bodies and the formation of vesicles in the stroma. We present evidence that the far-red block of greening is the result of severe repression of protochlorophyllide reductase (POR) genes by far-red light coupled with irreversible plastid damage. This results in the temporal separation of phytochrome-mediated POR; repression from light-dependent protochlorophyllide reduction, two processes that normally occur in coordination in white light.

Arabidopsis↗

Phytochrome signal-transduction: characterization of pathways and isolation of mutants.

The study of phytochrome signalling has yielded a wealth of data describing both the perception of light by the receptor, and the terminal steps in phytochrome-regulated gene expression by a number of transcription factors. We are now focusing on establishing the intervening steps linking phytochrome photoactivation to gene expression, and the regulation and interactions of these signalling pathways. Recent work has utilized both a pharmacological approach in phototrophic soybean suspension cultures and microinjection techniques in tomato to establish three distinct phytochrome signal-transduction pathways: (i) a calcium-dependent pathway that regulates the expression of genes encoding the chlorophyll a/b binding protein (CAB) and other components of photosystem II; (ii) a cGMP-dependent pathway that regulates the expression of the gene encoding chalcone synthase (CHS) and the production of anthocyanin pigments; and (iii) a pathway dependent upon both calcium and cGMP that regulates the expression of genes encoding components of photosystem I and is necessary for the production of mature chloroplasts. To study the components and the regulation of phytochrome signal-transduction pathways, mutants with altered photomorphogenic responses have been isolated by a number of laboratories. However, with several possible exceptions, little real progress has been made towards the isolation of mutants in positive regulatory elements of the phytochrome signal-transduction pathway. We have characterized a novel phytochrome A (PhyA)-mediated far-red light (FR) response in Arabidopsis seedlings which we are currently using to screen for specific phyA signal-transduction mutants.

Arabidopsis↗

Surgical palliation of unresectable pancreatic carcinoma.

The decision to perform surgical versus nonoperative palliation for unresectable pancreatic cancer is influenced by a number of factors. In most cases, patient symptoms clearly dictate the management. In patients with symptoms of duodenal obstruction at the time of presentation, surgery is the only option. In patients with obstructive jaundice alone, the options for management must be weighed against factors such as overall health status, projected survival, and procedure-related morbidity and mortality. A prospective multicenter trial recently analyzed factors influencing perioperative morbidity and mortality following both curative and palliative surgery for pancreatic cancer. This analysis demonstrated that preoperative diabetes, low Kanofsky's index, and liver metastases are significant risk factors in predicting perioperative morbidity and mortality in patients undergoing palliative procedures for pancreatic cancer. Another analysis focusing on tumor characteristics suggested that for patients with Stage I and Stage II disease (i.e., with no evidence of systemic metastases), survival and the potential for late duodenal obstruction favor surgical management. In summary, although patient management must be individualized, most patients with pancreatic cancer in good medical health and with no evidence of systemic disease are most appropriately managed with surgical palliation. This option affords patients the best chance of avoiding the late complications of recurrent jaundice, duodenal obstruction, and disabling pain. Surgical palliation can generally be completed with an acceptable perioperative morbidity and mortality and a hospital stay of approximately 2 weeks. Finally, only surgical exploration can offer full opportunity for resection for cure.

Cholestasis↗

Delayed-type hypersensitivity anergy in human immunodeficiency virus-infected persons screened for infection with Mycobacterium tuberculosis.

A total of 479 human immunodeficiency virus (HIV)-infected persons at an HIV clinic in Florida and a tuberculosis clinic in New Jersey were skin-tested with tuberculin, tetanus toxoid, mumps antigen, and Candida antigen in a study of the prevalence of delayed-type hypersensitivity (DTH) anergy and the usefulness of two-step tuberculin testing in this population. Of the patients tested, 12% had a positive (> or = 5-mm) response to tuberculin; 57%, 45%, and 35% had a positive (> or = 3-mm) response to Candida antigen, tetanus toxoid, and mumps antigen, respectively; and 31% were anergic (< 3 mm of induration in response to each antigen). In a multivariate logistic regression model, anergy was significantly associated with a history of Kaposi's sarcoma, Pneumocystis carinii pneumonia, or oral candidiasis and with White race. Anergy was four times and 15 times as likely for persons with CD4+ T-lymphocyte counts of 200-400/mm3 and < 200/mm3, respectively, as for persons with > 499 CD4+ T lymphocytes/mm3. Of 103 patients who were tuberculin-tested a second time after their initial test result was negative, seven had > or = 5 mm of induration in response to the second test; only one of these patients was anergic at the initial screening. The findings of this study indicate that DTH antigens should be used in conjunction with tuberculin testing and that two-step tuberculin testing is not an alternative to anergy testing but may be useful for the detection of infection with Mycobacterium tuberculosis in nonanergic HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Juvenile chronic arthritis: a cephalometric analysis of the facial skeleton.

A retrospective cross-sectional cephalometric investigation was undertaken to examine the facial form of a group of Finnish children with juvenile chronic arthritis (JCA). Following digitization, the radiographs were divided into three age groups, and according to whether or not 'bird-face' deformity was present. From a total of 67 cases (39 females and 28 males) 19 per cent were judged to be 'affected'. Analyses were carried out and the groups compared using t-tests. The mandible was found to be smaller both in ramal height and body length in the affected sample, with reduction in posterior face height being only partly compensated by increase in bony apposition at the angle producing antegonial notching. There was posterior rotation of the mandible with a reduction in angles S-N-B and S-N-Pog, and an increase in the gonial angle, the angle between the mandibular plane and S-N, maxillary, and occlusal planes. The changes in the maxilla were less marked. Although S-N-A was reduced in all three age groups, it was not significantly so. Maxillary length (ANS-PNS) was significantly smaller in the two younger age groups. In the vertical plane maxillary dimensions were reduced in the two younger age groups. A highly significant increase in the occlusal to maxillary planes angle was observed in all groups. There was, however, no difference in S-N to maxillary planes angle, indicating a more steeply inclined occlusal plane due to subnormally erupted maxillary molars. Although the inter-incisal angle was reduced there was no significant difference in the incisor inclinations in relation to the jaws and despite the posterior rotation of the mandible there was no significant increase in size of overjet or in the frequency of anterior open bite.

Adolescent↗

Treatment of prehospital refractory ventricular fibrillation with bretylium tosylate.

Among 218 patients treated for prehospital arrest during an eight-month baseline period prior to addition of bretylium tosylate to the paramedic protocol in Columbus, 16 (7.3%) were seen with refractory ventricular fibrillation (RVF). These patients failed to respond to multiple countershocks, lidocaine, bicarbonate and epinephrine, and either were transported in arrest during cardiopulmonary resuscitation (CPR)(14) or were pronounced dead at the scene (2). A single patient was eventually resuscitated in and discharged from the hospital. During the subsequent 16 1/2-month experience with bretylium used only for prehospital RVF, 421 patients with prehospital arrest were seen, 35 of whom (8.3%) had RVF. All but five patients were defibrillated successfully, and 14 (40%) were converted to a rhythm sufficient to obviate CPR during transportation. Eleven patients (31%) survived to be admitted to the hospital, and eight of 35 (23% vs 1/16 or 6.2% above, P less than .05) were discharged and remained well three to 17 months later. Bretylium tosylate may provide life-saving therapy for refractory prehospital ventricular fibrillation so that survival from an almost uniformly fatal condition is improved. While patients with persistent arrest generally should be transported to the hospital, such patients should not be subjected to the difficulties of CPR in transit unless they are first given bretylium if RVF is present.

Bretylium Compounds↗