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Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 667 records · Page 37Linked to original sources

The use of water-soluble radical scavengers to detect hydroxyl radical formation by polymorphonuclear leukocytes.

The polymorphonuclear leukocyte secretes both O2- and H2O2 when stimulated by various soluble or particulate stimuli. Since a reaction involving iron, O2-, and H2O2 could generate the hydroxyl radical (HO.) there has been speculation that the HO. may participate in the bactericidal activity of the neutrophil. A variety of water-soluble HO. scavengers have been used to test for the participation of HO. and the results imply that HO. might participate. However, other workers have not been able to detect the formation of significant amounts of HO. by the activated neutrophil. We have examined the effect of several commonly used HO. radical scavengers on the ability of the neutrophil to secrete O2- and H2O2. Several of these compounds actively inhibit secretion without affecting the viability of the neutrophil. After considering the various complications inherent in using water soluble radical scavengers, we suggest that they only be used with well defined experimental systems.

Allopurinol↗

Effects of several selected odorants on the sodium- and potassium-dependent adenosine triphosphatase activities of two different chicken olfactory tuberinals.

The NaK-adenosine triphosphatase (ATPase)-rich nerve-ending particle preparations (B fractions) of the epithelial tissue of chicken olfactory tubercle and the olfactory main concha were isolated by differential centrifugation. These tissues were exposed to the following odorants: 2-nonanone, 1-nonanol, 1-octanol, (+)2-octanol, and (-)2-octanol. There was a significant stimulation of NaK-ATPase by 2-nonanone (1 x 10(-3) M) in the B fraction of the olfactory tubercle and olfactory main concha. The NaK-ATPase increased significantly in the B fraction response of the olfactory main concha with 1 x 10(-3) M of 1-octanol but NaK-ATPase declined significantly in the presence of 1 x 10(-3) M of 1-nonanol. Both optical and structural isomers of odorants were shown to elicit different responses in NaK-ATPase activity. It is proposed that interactions between the odorant molecules and the membrane bound NaK-ATPase complex lead to recognition of odor by chickens.

1-Octanol↗

Tick infestations of white-tailed deer in Alabama.

Four species of ticks were collected from 537 white-tailed deer (Odocoileus virginianus), examined during the hunting seasons (November to January) of 1988-89 and 1989-90 at selected locations in Alabama (USA). Ixodes scapularis was the most common tick recovered (2,060 specimens) and infested 54% of the deer. Dermacentor albipictus was the second most frequent tick (1,253 specimens) and infested 15% of the deer. Amblyomma americanum was the third most frequent tick (315 specimens) and infested 24% of the deer; this was the only species of tick collected from deer at all sampling locations. Amblyomma maculatum was an infrequent parasite (five specimens) and infested only 1% of the deer; this tick species was only recorded during the 1989-90 season. Year-to-year and geographical differences in tick infestation parameters were noted. The data are compared with those reported for previous surveys of ticks infesting white-tailed deer in Alabama and adjacent states.

Alabama↗

HL7: facilitating multiple approaches to systems integration.

System interfaces of the 1980s are being replaced by system integration of the 1990s. Standards such as Health Level 7 (HL7) are facilitating this integration process. The authors dispel several persistent misconceptions about the HL7 standard and illustrate two working approaches to HL7-based networking.

Computer Communication Networks↗

Lack of transmission of the live attenuated varicella vaccine virus to immunocompromised children after immunization of their siblings.

The safety of administering the live attenuated Oka/Merck varicella vaccine to the well siblings of children with malignancy was evaluated as a strategy for reducing the risk of household exposure to varicella among immunocompromised children. Susceptible well children were eligible for vaccination if the child with malignancy had leukemia, lymphoma, or solid tumor in remission for 3 months or longer. No evidence of vaccine virus transmission was found among 30 children with malignancy whose 37 healthy susceptible siblings were immunized with varicella vaccine. Varicella-zoster virus was not isolated from the oropharyngeal secretions taken from 17 vaccinees or their 14 immunocompromised siblings. None of the 30 immunocompromised children had vaccine-related rashes or showed immunologic evidence of subclinical varicella-zoster virus infection based on testing for varicella-zoster virus IgG antibodies and T-lymphocyte proliferation to varicella-zoster virus. Four healthy vaccinees eventually had mild breakthrough cases of varicella, with transmission to the high-risk sibling in 3 cases. However, even in these families, the immunocompromised children had been protected from household exposure varicella for at least 20 months early in the course of their immunosuppressive treatment.

Adolescent↗

Bacterial translocation in trauma patients.

Sepsis and multiple system organ failure (MSOF) are major causes of morbidity and mortality in trauma patients. Bacterial translocation induced by hypotension, endotoxemia, or burns is a reproducible phenomenon in the laboratory. The incidence of bacterial translocation to mesenteric lymph nodes (MLNs) in 29 critically ill patients was evaluated to determine its relationship to subsequent sepsis and MSOF. Bacterial translocation was documented in 3 of 4 patients who underwent laparotomy for gastrointestinal (GI) disease. No trauma patient (25 patients), even at second exploration 3-5 days after injury, had a positive MLN culture. Five patients died; 4 trauma patients, one with GI disease. Forty percent of the trauma patients had major complications, predominantly pulmonary infections with gram-negative bacteria. However, infectious complications and outcome were not related to MLN culture results. The classical progression of bacteria from the gut to the bloodstream via the MLNs may require time and gut mucosal injury. The data suggest that bacterial translocation to the MLNs is not a common occurrence in acutely injured trauma patients.

Bacterial Physiological Phenomena↗

Right atrial catheters in children with cancer: a decade of experience in the use of tunnelled, exteriorized devices at a single institution.

In the period 1980-1988, data were collected (prospectively from 1985) on the clinical utilization of exteriorized, tunnelled, right atrial catheters in children with cancer undergoing treatment at a single institution. A total of 231 devices were placed in 180 patients. Individual catheters were in place for a median of 314 days, with a total experience of more than 83,000 days. This form of long-term venous access was used for the administration of antineoplastic agents and other drugs, blood products (especially platelet concentrates and packed red blood cells), parenteral nutrition and infusion of other fluids, obtaining samples of venous blood, and giving intravenous contrast media and radiolabeled substances for radiological investigations. Almost 80% of catheters were removed electively (on completion of scheduled therapy or at death), with the remainder requiring removal in the management of infection or device displacement. Infections were manifest in two-thirds of the children, most commonly (60%) at the catheter exit site on the anterior chest wall. "Clinically significant" infection occurred with a frequency of 2.1 episodes per 1,000 patient days, with Staphylococcal species predominating except for the circumstances of catheter colonization in which Gram-negative, waterborne organisms were most in evidence. Empirical, intravenous, combined antibiotic therapy was effective in approximately 90% of "clinically significant" episodes. Mechanical complications (traveling, leakage, or catheter occlusion) occurred less frequently and were managed by repairing or replacing the device, or clearing the block. Indwelling catheters, of the Broviac or Hickman types, offer major advantages with acceptable morbidity in the management of children with malignant diseases.

Adolescent↗

Inhibition of interleukin-2-induced tumor necrosis factor release by dexamethasone: prevention of an acquired neutrophil chemotaxis defect and differential suppression of interleukin-2-associated side effects.

High concentrations of tumor necrosis factor (TNF) alpha have been detected in the plasma of patients undergoing immunotherapy with interleukin 2 (IL-2), suggesting that this cytokine may play a role in the fever and shocklike state induced by the administration of high-dose IL-2. Dexamethasone has been shown to inhibit the synthesis of TNF by monocytes activated in vitro by endotoxin. To determine if dexamethasone can exert a similar suppressive effect on IL-2-induced TNF synthesis in vivo, the concentration of TNF alpha was measured in plasma samples serially obtained (a) from cancer patients participating in a phase I dose escalation clinical trial with high-dose IL-2 administered in conjunction with dexamethasone (IL-2/Dex) and (b) from patients participating in concurrent studies with IL-2 alone. In contrast to the high plasma levels of TNF alpha detected in patients receiving IL-2 alone, TNF levels in most of the IL-2/Dex patients remained below the threshold of detectability of our TNF radioimmunoassay. The concurrent administration of dexamethasone also prevented the IL-2-induced increase in serum levels of C-reactive protein, a hepatic acute phase reactant whose synthesis is regulated by proinflammatory cytokines such as TNF. The steroid-treated patients also failed to develop the neutrophil chemotactic defect characteristic of IL-2 recipients. The concomitant administration of dexamethasone increased the maximum tolerated dose of IL-2 approximately threefold and markedly reduced the hypotension and organ dysfunction ordinarily observed in these patients. These results demonstrate that dexamethasone inhibits the release of TNF into the circulation of patients undergoing immunotherapy with IL-2. They further suggest that the altered spectrum and reduced severity of IL-2 side effects observed in patients receiving dexamethasone may be attributable in part to the suppressive effect of steroids on IL-2-induced TNF synthesis.

C-Reactive Protein↗

Molecular cloning of the mammalian fatty acid synthase gene and identification of the promoter region.

Rat genomic clones encompassing the entire fatty acid synthase gene have been isolated and characterized. The gene is present in a single copy of approx. 20 kb. Genomic DNA sequencing, direct RNA sequencing and S1 nuclease analysis showed that transcription is initiated primarily 1274 nucleotides upstream from the translation start site and that the 87-nucleotide-long 5'-untranslated mRNA sequence is the same in liver, lung and mammary gland. The 5'-flanking region and first intron contain several sequence elements which may be involved in the transcriptional regulation of this gene.

Animals↗

Cytogenetic analysis of a plexiform fibrohistiocytic tumor.

A plexiform fibrohistiocytic tumor was analyzed cytogenetically after short-term in vitro culture. The stemline karyotype of this tumor was interpreted as 46,XY, -6, -8,del(4)(q25q31), del(20)(q11.2), + der(8)t(8;?)(p22;?), + mar. We believe this to be the first report of chromosome findings in this recently described histological entity.

Chromosome Aberrations↗

Prevention of iron deficiency in preterm neonates during infancy.

The preterm infant inevitably develops iron deficiency unless supplementary iron is given. Oral iron supplementation is preferred in ideal social circumstances but, where compliance with such therapy is uncertain, intramuscular iron dextran may be a more effective treatment. A study was conducted to compare the effectiveness of two methods of preventing iron deficiency of prematurity. One group of healthy premature infants was given oral iron 2 mg/kg/d until the age of 6 months. The second similar group was given 100 mg as intramuscular iron dextran (Imferon; Fisons) between the ages of 6 and 8 weeks. Both kinds of supplementary iron appeared to have benefited the majority of infants in this trial.

Anemia, Hypochromic↗

The carboxyl-terminal region of thioesterase II participates in the interaction with fatty acid synthase. Use of electrospray ionization mass spectrometry to identify a carboxyl-terminally truncated form of the enzyme.

Medium-chain S-acyl fatty acid synthase thioester hydrolase (thioesterase II), a discrete 263-residue serine active-site enzyme, modifies the product specificity of the de novo lipogenic pathway in certain specialized tissues by hydrolyzing the thioester bond linking the growing acyl chain to the 4'-phosphopantetheine of the fatty acid synthase. Modification of one thioesterase II cysteine thiol with thionitrobenzoate inhibited interaction with the S-acyl-fatty acid synthase substrate but not with acyl-CoA model substrates. The identity of the sensitive cysteine residue was determined by treatment of the thionitrobenzoyl enzyme with cyanide and cleavage at the amino-terminal side of the S-cyanocysteinyl residue. Two small cleavage products were isolated; their molecular masses (889 and 675 Da) and amino acid compositions indicated that both originated from cleavage at Cys256. A new technique of electrospray ionization mass spectrometry was utilized to confirm that the heterogeneity displayed by the products of S-cyanocysteinyl cleavage resulted from the presence, in the purified preparations, of both full-length and a truncated form of the enzyme missing the carboxyl-terminal Leu-Thr peptide. The proportion of full-length polypeptide present appeared to correlate with the activity of the enzyme toward its natural substrate. The results of modification of Cys256 by thionitrobenzoate and removal of residues 262 and 263 by endogenous proteases indicate that integrity of the carboxyl-terminal region is important for interaction with its acyl-fatty acid synthase substrate.

Acyl Coenzyme A↗

Protein binding, sister chromatid exchange and expression of oncogene proteins in patients treated with cisplatinum (cisDDP)-based chemotherapy.

The aim of this pilot was to evaluate the feasibility of incorporating several complementary biologic markers into a molecular epidemiologic study of chemotherapy patients. Thirty-two cancer patients being treated with cis-DDP-based chemotherapy for the first time were enrolled in the study and donated a baseline sample and at least one post-treatment sample of blood. Sister Chromatid Exchange (SCEs) and plasma protein and hemoglobin binding by cisDDP were significantly increased in samples drawn at various timepoints following treatment. The pattern of nine different oncogene protein products (including those of ras, fes, and myc) remained unchanged in sera of six patients followed over the course of their treatment. However, the levels of ras P21 product were significantly elevated above normal, control levels in all six cancer patients--both prior to and throughout the course of chemotherapy. These results suggest the usefulness of utilizing a battery of markers to evaluate biologic response to cisplatinum-based chemotherapy.

Aged↗

Ammonia as a potential mediator of adult human periodontal infection: inhibition of neutrophil function.

Neutrophils (polymorphonuclear leucocytes) are the principal cell of the host defence system. Consequently, if periodontal pathogen-derived substances in the gingival crevice significantly inhibit their function, they could shift the bacterial-host balance in favour of the bacteria. The hypothesis that ammonia can inhibit neutrophil function was tested. Ammonia was specifically selected because periodontal pathogens produce substantial amounts of ammonia. The findings indicated that ammonia can inhibit neutrophil phagocytosis, degranulation and oxygen metabolism. Ammonia decreased the total number of phagocytosing polymorphonuclear neutrophils (66% of control) and also decreased degranulation (61% of control). Ammonia decreased oxygen metabolism of both resting and stimulated neutrophils (33 and 42% of control, respectively). These observations support the hypothesis that ammonia can inhibit the function of polymorphonuclear leukocytes. They suggest that the presence of ammonia in the gingival crevice may increase the risk of development of periodontal disease.

Adult↗