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Biomedical subjects

V Scott

Publications and source records attributed to V Scott.

At least 19 recordsLinked to original sources

Intravenous peptide YY3-36 and Y2 receptor antagonism in the rat: effects on feeding behaviour.

Systemic injection of peptide YY3-36 reduces food intake in rodents and humans, although some groups have reported a lack of response. PYY3-36 is thought to act via the Y2 receptor to presynaptically inhibit the release of neuropeptide Y and GABA from hypothalamic arcuate neurones. Due to the controversy surrounding its action in rodents, we tested the peptide intravenously on feeding behaviour in rats and attempted to block its actions with the Y2 receptor antagonist BIIE0246. PYY3-36 significantly decreased food intake during the first hour in male Sprague-Dawley rats fasted overnight and then re-fed. BIIE0246 had no effect alone on re-feeding, but completely blocked the action of PYY3-36. In a second experiment of similar design, the behavioural satiety sequence (BSS) was studied. Normal rats eat, drink, explore and groom before entering rest. PYY3-36 significantly reduced food eaten maintaining the normal BSS, although shifting it to the left as expected for a natural satiety factor. The latency to rest occurred earlier for animals given PYY3-36 alone and PYY3-36 tended to increase the total time in rest compared with controls. These behavioural effects of PYY3-36 were blocked by BIIE0246, and BIIE0246 alone did not have an effect on the BSS. These results support the role of PYY3-36 as a natural satiety factor acting through Y2 receptors.

Animals↗

Spontaneous gram-negative cellulitis in a liver transplant recipient.

A 47-year-old liver transplant recipient developed fever and cellulitis on the 8th post-transplant day. The clinical appearances were of a rapidly advancing cellulitis. The patient had a past history of severe peripheral edema and hypoalbuminemia. Blood cultures and skin biopsy grew Escherichia coli. To our knowledge, this is the first reported case of E. coli cellulitis in a liver transplant recipient. However, cases have previously been described in patients with cirrhosis or idiopathic nephritic syndrome, conditions which share predisposing features of peripheral edema and hypoalbuminemia. Bacteremic gram-negative cellulitis should be considered in compromised patients with unusual presentations of cellulitis.

Biopsy↗

Intracardiac thrombus formation and pulmonary thromboembolism immediately after graft reperfusion in 7 patients undergoing liver transplantation.

Intravascular and/or intracardiac thrombus formation followed by pulmonary thromboembolism with right ventricular dysfunction immediately after graft reperfusion during orthotopic liver transplantation (OLT) is described in 7 patients. This complication may have been related to excessive activation of the coagulation system by graft reperfusion, which overwhelmed anticoagulation mechanisms and was disproportionate to fibrinolysis. Activation of the coagulation system may be more pronounced in patients who receive less than optimal grafts, require massive transfusion, or have septic complications at the time of OLT. It is unclear whether antifibrinolytic therapy during the anhepatic stage had a role. Transesophageal echocardiography was useful in diagnosing and managing intracardiac thrombus and pulmonary thromboembolism.

Adult↗

In planta regulation of extension of an endophytic fungus and maintenance of high metabolic rates in its mycelium in the absence of apical extension.

The fungus Neotyphodium lolii is an endophytic symbiont. It grows in the intercellular spaces of the perennial ryegrass Lolium perenne, producing secondary metabolites which enhance the fitness of the association over that of uninfected L. perenne. We report that the average number of hyphal strands in a given section of a leaf remains constant during the life of a leaf, indicating synchrony of leaf and hyphal extension, including cessation of hyphal extension when leaf extension ceases. We used a constitutively expressed reporter gene as an indicator of the mycelium's metabolic activity during and after hyphal extension. Reporter gene activity decreased when the mycelium stopped extending in liquid culture but not in planta. This indicates that in planta endophyte hyphae remain metabolically highly active when extension has ceased and throughout the life of the leaf they are colonizing. The behavior of the fungus in planta indicates the existence of signaling pathways which (i) synchronize the extension of leaf and hypha by regulating hyphal extension, (ii) suppress hyphal branching, and (iii) stop apical extension of fungal hyphae, without reducing the mycelium's metabolic activity. These signals may be crucial for the symbiosis, by allowing the endophyte to switch the focus of its metabolic activity from extension to the production of secondary metabolites.

Ascomycota↗

Intravenous propofol: unique effectiveness in treating intractable migraine.

OBJECTIVE: To report the unique effectiveness of propofol, an intravenous anesthetic agent, in treating refractory migraines and other headaches in the setting of an outpatient headache center. BACKGROUND: We initially observed the dramatic abolition of ongoing migraine in patients (n=6) being treated with propofol in preparation for epidural and other nerve blocks in the headache and pain clinic. The reduction of headache severity was virtually 100%. We decided to treat an additional cohort of patients with intravenous propofol in the headache clinic; these patients had intractable migraines that were refractory to the usual abortive treatments. Subanesthetic doses of propofol were employed in this study. This is the first known report of the utility of this agent specifically for the treatment of intractable headache. METHODS: Seventy-seven patients were treated for intractable headache in the clinic with intravenous propofol, for both migraine and nonmigrainous headache refractory to the usual methods of abortive treatment. RESULTS: The average reduction in headache intensity was 95.4% after an average of 20 to 30 minutes of intravenous propofol treatment, using a patient-rated visual analog scale of 0 to 10. Sixty-three of 77 patients reported complete abolition of their headache. The average dose of propofol was 110 mg, which is well within the usual range of preanesthetic doses and is clearly subanesthetic. Moreover, only three of the treated patients reported a return of the headache on the day following treatment. The neuropharmacology of propofol and the putative multiple mechanisms of action upon various neurotransmitter systems in the brain, particularly gamma aminobutyric acid A receptor subtypes, are discussed to explain the results in our patients. CONCLUSIONS: The use of intravenous propofol may represent a new, rapid, and highly effective form of abortive headache treatment in the headache clinic or emergency room setting and may offer an alternative to other treatment modalities for acute migraine and other severe intractable headaches. The effectiveness of propofol raises many new questions about the pathophysiology of migraine and other headaches.

Anesthetics, Intravenous↗

The relationship of disease severity, health beliefs and medication adherence among HIV patients.

The objective was to investigate the relationship of disease severity, health beliefs and medication adherence among HIV/AIDS patients. A survey was administered to 72 patients in three different stages of HIV/AIDS (CDC clinical categories A, B, C). Multivariate analyses revealed that there were no significant differences in patients' perceptions of the severity of HIV/AIDS or perceptions of the benefits and barriers for the treatment across three disease stages. However, the most severely ill patients (in stage C) perceived a higher risk of complications if they did not take their medicine as prescribed compared to asymptomatic patients (stage A) (p = 0.01). Also, patients in stages B and C were more adherent to their medications compared to patients in stage A (p = 0.007). Finally, perceived susceptibility-inaction was positively related to medication adherence (p = 0.005) and difficulty in following doctors' instructions was negatively related to patients' medication adherence (p = 0.009). In conclusion, patients' illness experiences are associated with their beliefs about the chances of developing complications if they do not adhere to their medications. Patients who have experienced more complications perceive a stronger relationship between medication non-adherence and AIDS-related complications, and are also more adherent to their medication regimen when compared to patients with no prior complications.

Acquired Immunodeficiency Syndrome↗

A hsp70-2 mutation recognized by CTL on a human renal cell carcinoma.

We performed T cell cloning experiments with a tumor-infiltrating lymphocyte subpopulation derived from a renal cell carcinoma tumor site (RCC-7) in which the TCR clonotypic repertoire had been analyzed in terms of TCRBV complementarity-determining region 3 size distribution. We report in this work the characterization of one of the five RCC-specific MHC class I-restricted CTL clones isolated in RCC-7. This TCRBV6J1S1 CTL recognized only the autologous RCC-7 tumor cell line in the context of HLA-A*0201, and the Ag is encoded by a mutated form of the hsp70-2 gene found in the tumor cells, but not in autologous PBLs nor in 47 other tumors. The identification of this gene was achieved by cotransfecting into COS cells a cDNA library of RCC-7 together with HLA-A*0201. Transfectants expressing the Ag were identified by their ability to stimulate TNF release by the CTL clone. The antigenic peptide is a decamer with a mutated residue at position 8. Half-maximal lysis was obtained with only 5 x 10(-11) M of decapeptide in target sensitization assays compared with 5 x 10(-8) M for the wild-type decapeptide. This difference in recognition was not related to difference in binding HLA-A*0201-presenting molecules, as assessed in an immunofluorescence-based peptide-binding assay using T2 cells. Constitutive hsp70 expression in various tumors suggests that this stress-induced protein may be recognized in situ by tumor-infiltrating lymphocytes. The finding in the tumor of a mutated form of the stress-induced hsp70-2 gene whose product is specifically recognized by TILs with high avidity is discussed in view of the present use of mycobacteria or heterologous heat-shock proteins as immunomodulators or as subunit vaccine candidates.

Animals↗

Belt worn control system and battery for the percutaneous model of the Jarvik 2000 heart.

A belt worn controller and lithium-ion battery pack have been developed for use with the initial clinical trials of the Jarvik 2000 heart. Patient interface considerations, safety, and simplicity were major design inputs for the system. The controller was developed using all analog technology to avoid difficulties with electromagnetic interference (EMI), to minimize susceptibility to electrostatic discharge, and to avoid the need for software validation. Manual control of pump speed is accomplished by a patient operated knob, according to physician instructions for rest and exercise for each individual patient. The system includes alarms and indicators which show the following: the amount of remaining battery charge, if the battery is low and needs replacement, the power in watts being consumed, if the power consumed is above 15 W, if the pump is running below the selected speed setting, and if the pump stops. The control box, curved to be worn on the belt, is only 2.5 inches high for comfort when sitting. The battery pack, also form fitted for patient comfort, weighs just over 1 1/2 pounds and supplies 65 W-h of energy storage, sufficient to run the device for over 8 h at nominal load.

Computers, Analog↗

Differences between African American and Caucasian men participating in a community-based prostate cancer screening program.

Prostate cancer is a major contributor to morbidity and mortality in the male population, but public awareness of the cancer has been reported as minimal. We evaluated the effectiveness of an educational prostate cancer screening program on 944 men in a midwest urban community. Digital rectal examinations and PSA blood tests were provided at no charge to participants with a grant from the Michigan Department of Community Health. An educational intervention that stressed the importance of prostate cancer early detection and treatment was conducted before screenings. A brief questionnaire administered before and after the videotape and screenings, targeted both knowledge and attitudes concerning prostate cancer. Pre-test results revealed that African American men were significantly (t = 3.7, P = .00) less likely then white men to correctly identify early symptoms of prostate cancer and the basic components of a prostate checkup. Following program involvement, scores significantly improved in all areas and differences were no longer significant between the races. Racial differences were also found for screening preferences and modes of reaching men to participate in screening. African American men were twice as likely as white men to choose private appointments over mass screening (OR = 2.2, P = .00). Radio reached the most African Americans (25%) while newspaper reached the most Caucasians (34%). The decreased level of knowledge among African Americans regarding prostate etiology and clinical factors highlights the need for educational programs to target minority populations. The need for discretion also applies by providing minority-favored access with screening through private appointments.

Adult↗

Mapping of X-linked myxomatous valvular dystrophy to chromosome Xq28.

Myxoid heart disease is frequently encountered in the general population. It corresponds to an etiologically heterogeneous group of diseases, idiopathic mitral valve prolapse (IMVP) being the most common form. A rarely observed form of myxoid heart disease, X-linked myxomatous valvular dystrophy (XMVD), is inherited in an X-linked fashion and is characterized by multivalvular myxomatous degeneration; however, the histopathological features of the mitral valve do not differ significantly from the severe form of IMVP. In this article, we describe the genetic analysis of a large family in which XMVD is associated with a mild hemophilia A. The coagulation factor VIII gene position in Xq28 provided a starting point for the genetic study, which was conducted by use of polymorphic markers. Two-point linkage analysis confirmed this localization, and a maximum LOD score of 6.57 was found at straight theta=0 for two polymorphic microsatellite markers, INT-3 and DXS1008, the first one being intronic to the factor VIII gene. Haplotype analysis of this chromosomal region allowed the definition of an 8-cM minimal interval containing the gene for XMVD, between DXS8011 and Xqter.

Chromosome Mapping↗

gamma-tubulin in trypanosomes: molecular characterisation and localisation to multiple and diverse microtubule organising centres.

A genomic clone from Trypanosoma brucei, which contains a full length gamma-tubulin gene, was isolated using degenerate oligonucleotide primers. The sequence of this clone predicts a protein of 447 amino acids having a high degree of homology with gamma-tubulins from human and Xenopus laevis (67.2% amino acid identity) and only 57.7% identity with the Plasmodium falciparum gamma-tubulin. Northern blot analysis of poly(A)+ selected RNA from a procyclic culture detects a major transcript of approximately 2.2 kb plus a minor transcript of approximately 3.6 kb. A fusion protein comprising almost the full length gamma-tubulin gene product (amino acids 8-447) plus an amino-terminal histidine tag has been expressed and purified from Escherichia coli and used to raise a polyclonal antibody. Immunofluorescence, using this antibody, shows classical centrosomal localisation in mammalian cells. In T. brucei gamma-tubulin is present in the basal bodies which subtend the flagellum and also at the anterior tip of the cell body where many minus ends of microtubules are located. Furthermore the antibody reveals a small subset of the sub-pellicular microtubules and a discrete dot within the nucleus which alters form with progression through the mitotic cycle. Evidence is also presented for discrete punctate staining within the microtubules of the cell body which may represent the presence of gamma-tubulin on the ends of individual microtubules. Our results indicate that gamma-tubulin is associated with diverse microtubule organising centres and structures in trypanosomes.

Amino Acid Sequence↗

Hemodynamic effects of inhaled nitric oxide in four patients with severe liver disease and pulmonary hypertension.

Patients with moderate and severe pulmonary hypertension have a very high mortality rate when undergoing orthotopic liver transplantation. Because nitric oxide has been successful in reducing pulmonary artery pressures in certain patients with pulmonary hypertension, the efficacy of NO inhalation (40 and 80 ppm) in 4 patients with pulmonary hypertension associated with liver disease was determined. No clinically significant changes in pulmonary artery pressures or other hemodynamic parameters were observed using either concentration of NO. In conclusion, no pulmonary vasodilatory response from inhalation of NO in 4 patients with severe liver disease and pulmonary hypertension was found.

Adult↗

T-cell receptor repertoire in neuroblastoma patients.

Spontaneous regression of widespread lesions is a characteristic feature of neuroblastoma. One may postulate that the immune response contributes to these clinical regressions. Accordingly, we studied the T-cell receptor (TCR) repertoire of tumor-infiltrating lymphocytes in eight neuroblastoma tumors. The expression of 29 V alpha and 24 V beta gene segment subfamily specificities was analyzed by PCR and compared by computerized densitometry of Southern blots to values obtained in the blood. Overall, the TCR repertoire of these eight patients was diverse, with virtually all V alpha and V beta specificities expressed. Nonetheless, four of these patients showed V beta 2 gene segment subfamily overexpression in the tumor corresponding to local expansion of polyclonal T-cell subpopulations. In one patient, this expansion could be due to local secretion of superantigenic activity, as suggested by the specific stimulation of murine T cells expressing a human V beta 2 chain by supernatant of the corresponding neuroblastoma cell line. In addition, high-resolution analysis of the TCR beta transcript complementarity-determining region 3 sizes identified three patients (of six studied) with marked clonal T-cell expansion in the tumor not seen in the blood. The specific expression of several dominant clono-types in the tumor may be related to the recognition of neuroblastoma-specific antigens in these patients. Together, these results on the TCR repertoire expressed in vivo may lead to the characterization of putative immune response mechanisms (i.e., antigen- or superantigen-driven stimulation) which participate in tumor regression.

Animals↗

Altered endothelin homeostasis in patients undergoing liver transplantation.

The liver is a major site of synthesis, clearance, and actions of the powerful vasoactive peptide endothelin-1 (ET-1). We investigated the role of the liver in ET-1 homeostasis by comparing circulating and hepatic ET-1 levels and hepatic ET receptors in patients undergoing orthotopic liver transplantation (OLTx) for end-stage liver disease (ESLD) with those in patients undergoing liver resection for focal lesions with otherwise normal hepatic synthetic function. Central venous and radial arterial blood was drawn immediately after induction of anesthesia (point I), 10 minutes before beginning of resection or the anhepatic stage (point II), and 30 minutes after completion of resection or reperfusion of the grafted liver (point III). Portal and hepatic venous blood was drawn at points II and III. Plasma ET-1 levels were higher in ESLD patients than in resection patients. Plasma ET-1 levels rose both during resection and transplantation; the increase in ET-1 was more pronounced during transplantation. In ESLD patients, hepatic venous ET-1 was higher than portal venous ET-1, suggesting reduced clearance and/or enhanced synthesis of the peptide in the cirrhotic liver. Conversely, hepatic venous ET-1 was lower than portal venous ET-1 in resection patients at all time points and at point III in the ESLD patients. Hepatic concentration of ET-1 was greater and the capacity of the liver to catabolize ET-1 was reduced in ESLD patients as compared to the resection patients. Further, hepatic ET receptor density was higher in ESLD than in resection patients. These results suggest that the cirrhotic liver may contribute to elevated plasma ET-1 in ESLD. Considering its potent hemodynamic and metabolic effects in the liver, increased hepatic ET-1 and ET receptors and plasma ET-1 could play a role in the pathophysiology of liver disease and perioperative complications of OLTx.

Adult↗