Search PubMed⌕ Search

Biomedical subjects

S Norris

Publications and source records attributed to S Norris.

70 records · Page 4Linked to original sources
PubMed1987

Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes.

We have previously reported histamine desensitization of human blood mononuclear leukocytes resulting in reduced cAMP responses to beta-adrenergic agonists, histamine and prostaglandin E1. This heterologous desensitization occurred at low, micromolar histamine concentrations and was accompanied by elevation of cAMP-phosphodiesterase (PDE) activity in these cells. We have now investigated the activity of PDE in the lymphocyte and monocyte fractions of mononuclear leukocytes to determine the site of histamine effect. PDE activity per cell was higher in monocytes (0.075 +/- 0.070 units) than lymphocytes (0.026 +/- 0.08) units). Monocytes responded to 10(-6) M histamine stimulation with a much greater increase in PDE activity (0.354 +/- 0.1 units) than did lymphocytes (0.047 +/- 0.015 units). Histamine receptor studies, using thiazolylethylamine and chlorpheniramine as H1-agonist and antagonist respectively and dimaprit and cimetidine as H2-agonists and antagonists respectively, indicated that the histamine stimulation of PDE activity is mediated predominantly through H1 histamine receptor in the monocytes and the H1 receptor in the lymphocytes. Previously histamine had been thought to increase cyclic AMP by acting on H2 receptors to activate adenylate cyclase. Our studies show that stimulation of H1 or H2 receptors by low histamine concentration can cause the opposite effect i.e. increased catabolism and a net reduction in cAMP levels. The localization of this effect predominantly to monocytes indicates a potentially important mechanism for histamine action on immune regulation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1985

Effects of varied cardioplegic perfusion pressure on myocardial preservation with critical coronary stenosis.

Inadequate delivery of cardioplegic solution distal to coronary artery stenosis may result in increased injury during ischemic arrest. This study was performed to determine the effects of cardioplegic perfusion pressure on cardioplegia delivery and myocardial preservation in hearts with critical coronary artery stenosis. Twenty dogs underwent 90 minutes of cold potassium cardioplegic arrest with partial occlusion of the circumflex coronary artery. Group 1 received cardioplegia at 50 mm Hg pressure, Group 2 at 90 mm Hg pressure, and Group 3 at 130 mm Hg pressure. It was found that cooling rates were 5.4 degrees, 9.1 degrees, and 18.2 degrees C per minute in the nonischemic area (p = 0.004) and 2.0 degrees, 4.5 degrees, and 7.9 degrees C in the ischemic area (p = 0.008) in Groups 1, 2, and 3, respectively. Total of cardioplegic solution flows were 86, 188, and 262 ml per minute per 100 gm in Groups 1, 2, and 3, respectively (p = 0.001). However, flow did not differ significantly between groups in the ischemic area. Rate of rise of left ventricular (LV) pressure decreased significantly in Groups 1 and 2 but not in Group 3 (p = 0.002). Other measured variables did not differ significantly between groups, although LV function curves showed less deterioration in the high-pressure groups. It is concluded that higher cardioplegic perfusion pressure resulted in more rapid cooling in normal and ischemic areas and slightly better preservation of ventricular function as measured by some indexes. However, preservation was generally good for each of the pressures for up to 90 minutes of ischemia when the septum was consistently cooled to 10 degrees C.

Adenosine Triphosphate↗
PubMed1985

Nimodipine and chronic vasospasm in monkeys: Part 1. Clinical and radiological findings.

The efficacy of the calcium channel blocker nimodipine in the prevention of chronic cerebral vasospasm (VSP) and delayed ischemia after subarachnoid hemorrhage (SAH) in monkeys was examined in a blind, randomized, placebo-controlled trial. The primate model developed in this laboratory reliably induces chronic cerebral vasospasm and can induce pathologically proven delayed ischemic neurological deficits (DINDs). With standard microsurgical procedures, an average 6.4-ml autologous hematoma was placed directly against the major anterior cerebral vessels in the right basal subarachnoid spaces of 24 monkeys. The monkeys were randomized to one of four groups and were treated orally q8h for 7 days with nimodipine (3, 6, or 12mg/kg)or placebo. An additional 2 monkeys underwent the surgical procedure without clot placement. Drug administration began between 14 and 20 hours after clot placement. Indices monitored before and after SAH included neurological status, angiographic cerebral vessel caliber, and cerebral blood flow. Significant VSP (25 to 100% reduction in vessel caliber) was present on Day 7 on the clot side in 83% of the animals (P less than or equal to 0.001). There was no significant difference (P greater than 0.05) in the incidence of VSP among the four groups. Similarly, there was no significant difference (P greater than 0.05) in the mean vessel caliber reduction after SAH among the four treatment groups. There was no VSP present on Day 7 in the sham-operated animals. One animal receiving high dose nimodipine (12 mg/kg p.o. q8h) developed a DIND on Day 5 after SAH. A second animal in the 12-mg/kg group developed a transient neurological deficit between Days 4 and 7.

Animals↗
PubMed1985

Nimodipine and chronic vasospasm in monkeys: Part 2. Pharmacological studies of vessels in spasm.

The effect of nimodipine on the in vitro reactivity of cerebral vessels after subarachnoid hemorrhage (SAH) was studied. With the use of a primate model of chronic cerebral vasospasm, 12 female cynomolgous monkeys underwent the induction of a SAH by the direct placement of an average 6.4-ml autologous hematoma against the major anterior cerebral vessels in the right basal subarachnoid spaces (Day 0). The animals were then randomized to one of four groups and within 14 to 20 hours after clot placement were started on oral q8h therapy with nimodipine (3, 6, or 12 mg/kg) or placebo. On Day 7, the animals were killed and the right and left middle cerebral arteries (MCAs) were immediately resected and placed in oxygenated Krebs' solution. Ring preparations from the arteries were suspended in organ baths, and dose-effect curves to varying concentrations of norepinephrine, 5-hydroxytryptamine, and potassium chloride were obtained. There was a highly significant reduction in the response of the MCA on the clot side (right) relative to the nonclot side (left) to all three agonists. The clot side contractility was not influenced by nimodipine treatment at any of the four doses tested. The nonclot side arteries of the 12-mg/kg treatment group demonstrated significantly enhanced reactivity for all three agonists. Oral treatment with high dose nimodipine enhances the reactivity of normal cerebral vessels to the agonists tested, but it does not seem to affect the reactivity of arteries in chronic spasm at any of the four doses tested.

Animals↗
PubMed1979

Early diagnosis of disk space infection with 67Ga in an experimental model.

Both 67Ga and 99mTc scans become positive in experimental disk space infection, but 67Ga does so earlier than 99mTc. The radiologic features of experimental disk infection are similar to those seen clinically. Disk infection commences primarily in the disk and not in the vertebral body. Gallium-67 is useful in diagnosis of the disease under circumstances when the diagnosis is in doubt.

Animals↗
PubMed1978

Early diagnosis of disc-space infection using Gallium-67.

A 4-year-old boy had had progressive central lumbar pain and hamstring spasm. He had a normal lumbar-spine x-ray except for minimal L-5, S1 spondylolysis, but gave an abnormal gallium-67 scan in the region of the low lumbar spine. Eight weeks following intensive antibiotic therapy, confirmation of the diagnosis of disc-space infection was established by roentgenographic studies that demonstrated narrowing of the L 4-5 intervertebral disc space. A technetium-99m diphosphonate bone scan, performed concurrently with the gallium-67 study, was normal.

Bacterial Infections↗
PubMedDate not supplied

Acute renal failure in orthotopic liver transplantation.

Acute renal failure (ARF) is a frequent complication of orthotopic liver transplantation (OLT) and is a major cause of mortality and morbidity. We report the incidence, management and outcome of ARF in OLT patients during the first year of a liver transplant programme.

Acute Kidney Injury↗
PubMedDate not supplied

Interaction of spirochetes with the host.

The success of an invading organism must depend on several cytoplasmic, surface-associated and secreted factors. The technical difficulties in handling pathogenic spirochetes like Treponema pallidum and Borrelia burgdorferi have made it difficult to define specific factors involved in entry and long-term survival. The problem of defining virulence factors has been attacked by several strategies: T. pallidum secretes a number of immunogenic low molecular mass proteins. The most predominant are of molecular weight 15.5 and 22 kDa. Preliminary data suggest that antibodies against these proteins induce protective immunity in rabbits experimentally infected with T. pallidum. Many potentially important surface-associated antigens of T. pallidum have now been cloned and characterized. Two of these, TpD and TpE, are lipoproteins which exhibit characteristic size heterogeneity. The apparent molecular weight of TpE from T. pallidum and T. pertenue are different. The clinical symptoms in syphilis and yaws are very different, but sequence analysis of TpE has shown that the TpE proteins are indeed very similar in the two strains. This observation makes it unlikely that heterogeneity of TpE can account for the different clinical symptoms of syphilis and yaws. Sequence data for another newly sequenced surface-associated antigen of T. pallidum (molecular weight 41 kDa) indicate that this protein is involved in glucose transport and chemotaxis/motility. Intracellular factors like the molecular chaperonin GroEL have been documented both in treponemes and borreliae. This stress protein is involved in cellular repair processes and folding/assembly of protein subunits. Indirect evidence suggests that GroEL affects the ability of spirochetes to survive in the stressful environment of the infected host. Several lines of evidence suggest that the Osp proteins of Borrelia are important for host/parasite interaction. Further support for this idea has come from studies of a series of monoclonal antibodies against OspA. A monoclonal antibody against OspA (9B3D) is able to block attachment of B. burgdorferi to a cell monolayer. Borrelia loses infectivity after several passages in vitro. The loss of pathogenicity is associated with loss of specific plasmids and proteins. One of the low-passage-associated proteins (Lap30) has been cloned and sequenced. Lap30 is a lipoprotein encoded by a 38-kb plasmid, not present in high passage B. burgdorferi. Aberrant immunological processes induced by the lipopolysaccharide component of Treponema hyodysenteriae could explain the dramatic intestinal lesions in swine dysenteriae. But analysis by TLC reveals that the LPS of this treponeme is different from classical Salmonella LPS.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Outer Membrane Proteins↗
PubMedDate not supplied

Digital intravenous ventriculography. Comparison of volumes from mask-mode and nonsubtracted images with thermodilution and sonocardiometric measurements.

Left ventricular volumes calculated from mask-mode (MM) images obtained by digital intravenous ventriculography (DIV) were compared with volumes determined from direct contrast images (CV), thermodilution and sonomicrometer measurements in six anesthetized dogs in which volumes were varied by isoproterenol and phenylephrine infusions. Short and long axis sonomicrometer crystals allowed continuous measurement of cardiac size and function. The MM and CV ejection fractions and volumes correlated well with each other (r greater than or equal to 0.96) through the MM volumes consistently underestimated the CV volumes by 12 +/- 3%. Analyzing each dog individually, both CV and MM volumes and ejection fractions correlated well with sonomicrometer results. In addition CV and MM estimates of stroke volume correlated well (r greater than or equal to 0.91) with the thermodilution values, although the CV values exceeded the thermodilution value by 17 +/- 4%. We conclude that MM analysis of left ventricular function correlates well with standard measures of cardiac dimensional changes and agrees with, though underestimates, the simultaneous nonsubtracted contrast ventriculographic images.

Animals↗
PubMedDate not supplied

T lymphocyte subsets and activation status in patients following liver transplantation.

Changes in T-lymphocyte subsets have previously been shown to relate to clinical events following liver transplantation and be of prognostic significance following renal transplantation. The aim of this study was to examine T lymphocyte subsets, their activation status and the mean fluorescence intensity of cell surface markers by flow cytometric analysis, in peripheral blood of patients following liver transplantation. Stable transplant patients (n=11) had a significantly higher level of activation (HLA-DR expression ) of all T cell subsets: CD3, CD4 and CD8 compared to healthy controls: 17.5% +/- 14.0 (mean +/- SD) vs 4.7 +/- 1.8 (p=0.04), 13.7% +/- 10.3 vs 4.3 +/- 1.7 (p=0.03) and 23.8% +/- 19.9 vs 3.6 +/- 2.4 (p=0.02) respectively. A further increase in activation status occurred in all T cell subsets in association with acute cellular rejection, reaching significance for the CD4+ population: 13.7% +/- 10.2 vs 23.3% +/- 20.6 (p=0.04). The mean fluorescence intensity of the CD3+DR- and CD3+ DR+ populations were increased to 1397 +/- 869 and 1282 +/- 810 following liver transplantation compared to values of 425 +/- 204 and 376 +/- 166 respectively for controls (p<0.05). T-lymphocytes maintain a high level of activation following liver transplantation and continue to express high levels of the surface marker CD3, which may account for the occurrence of acute cellular rejection despite immunosuppression in these patients.

Adult↗
PubMedDate not supplied

Diagnosis of acute cardiac rejection with antimyosin monoclonal antibody, phosphorous nuclear magnetic resonance imaging, two-dimensional echocardiography, and endocardial biopsy.

A cervical heterotopic cardiac allograft model was used to compare noninvasive techniques with endocardial biopsy diagnosis of rejection. The transplant procedure was performed in eight dogs (12 to 16 kg), with a mean ischemic time of 83 minutes. Beginning on the day of the operation each allograft was evaluated daily by palpation, two-dimensional echocardiography, phosphorous nuclear magnetic resonance spectroscopy, and septal endocardial biopsy. At specific intervals after the operation, antimyosin monoclonal antibody (Fab fragment) with an indium-111 label was administered for subsequent gamma camera imaging. Rejection was clinically evident by 2 to 8 days with a mean of 3.5 days. Endocardial biopsy demonstrated moderate to severe rejection by 2 to 4 days. Two-dimensional echocardiography demonstrated early loss of wall thickening dynamics in all allografts. Although subtle changes were evident early in some transplants, these findings were not consistent. After recovery from hypothermic ischemia, evaluation of high energy phosphate metabolites with phosphorous nuclear magnetic resonance spectroscopy showed a progressive decrease in phosphocreatine during mild to moderate rejection, dropping to 30% to 40% of baseline levels with severe rejection. Antimyosin antibody uptake directly correlated with endocardial biopsy rejection scores (R2 = 0.97). With mild to moderate rejection, mean total counts and corrected counts were 222,704 and 112,648, respectively, and were significantly different (p less than 0.05) from baseline counts (135,537 and 58,530) without rejection. As a preliminary finding in untreated acute rejection, both antimyosin antibody and phosphorous nuclear magnetic spectroscopy detected changes consistent with mild to moderate rejection, which usually preceded echocardiographic evidence for injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Nursing procedures and alterations in transcutaneous oxygen tension in premature infants.

This study evaluated the effects of three routine nursing procedures--suctioning, repositioning, and performing a heelstick--on blood oxygen levels in premature infants, using a transcutaneous oxygen (Tcp02) monitor. Twenty-five infants with respiratory distress syndrome were monitored for three hours during which all three procedures were performed. Continuous Tcp02 records were used for measurement of baseline Tcp02 degree and duration of Tcp02 changes, length of procedural time, and rest time prior to procedures. Data were analyzed to determine if Tcp02 was altered during routine procedures, and if the degree of change was affected by length of procedure or length of rest prior to a procedure. Degree of Tcp02 change was analyzed in relation to length of time taken to recover from procedures. Tcp02 was decreased significantly during suctioning and repositioning but not during heelstick. The three procedures resulted in different degrees of change in Tcp02. Suctioning elicited the greatest decrease, followed by respositioning then heelstick. Recovery time was related to the degree of change in Tcp02 only after the repositioning procedure. Length of procedure and rest time did not relate to the degree of change in Tcp02, suggesting that it was the type of procedure that determined infant response.

Adaptation, Physiological↗