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Biomedical subjects

C M Nelson

Publications and source records attributed to C M Nelson.

At least 37 records · Page 2Linked to original sources

Feeding formula without arachidonic acid and docosahexaenoic acid has no effect on preferential looking acuity or recognition memory in healthy full-term infants at 9 mo of age.

Preferential looking acuity and novelty preference (a test of recognition memory) were determined by using Teller Acuity Cards and the Fagan Test of Infant Intelligence, respectively, for 399-433 healthy full-term infants at 39 +/- 1 wk of age. Duration of breast-feeding and age of infant at introduction and amount and type of formula were determined by questionnaire. Seventy-four infants (17%) were never breast-fed; another 92 infants (21%) were still receiving breast milk as the milk source at 39 wk of age. There were no differences in visual acuity or novelty preference among the infants when they were stratified by incidence or duration of breast-feeding. The formulas met current Canadian guidelines with > or = 0.7% of energy as linolenic acid, but had no docosahexaenoic or arachidonic acid. The studies indicate that formulas containing adequate linoleic and linolenic acids, without arachidonic or docosahexaenoic acid, impose no measurable deficits in performance in these visual and cognitive developmental tests at 9 mo of age in healthy full-term infants.

Arachidonic Acid↗

Isolation of the equine granulocytic ehrlichiosis agent, Ehrlichia equi, in tick cell culture.

The equine granulocytic ehrlichiosis agent, Ehrlichia equi, is closely related or identical to the human granulocytic ehrlichiosis (HGE) agent. Both are suspected of being transmitted by ticks. We have successfully isolated E. equi in a cell line, IDE8, derived from a putative vector, the tick Ixodes scapularis. Peripheral blood leukocytes from an experimentally infected horse were inoculated onto IDE8 monolayers. Cultures were incubated in a candle jar at 34 degrees C in tick cell culture medium with NaHCO3 and an organic buffer [3-(N-morpholino)-propanesulfonic acid] (MOPS). Within 2 weeks, infected cells were detected in Giemsa-stained culture samples, and the organisms subsequently spread to uninfected cells in the cultures. E. equi was passaged serially by transferring a portion of an infected culture to new cell layers every 2 to 3 weeks. The identity of the organisms was confirmed by PCR using oligonucleotide primers specific for E. equi and the HGE agent and by immunocytology. Homologous equine antibodies and human anti-HGE convalescent serum recognized E. equi grown in tick cell culture. Electron microscopy revealed electron-lucent and -dense ehrlichia-like forms developing within host cell endosomes. E. equi passaged twice in tick cell culture retained infectivity and pathogenicity for the equine host, as demonstrated by intravenous inoculation of a suspension of infected tick cells and subsequent reisolation from peripheral blood, in fulfillment of Koch's postulates. The horse developed severe clinical signs, i.e., fever, inappetence, thrombocytopenia, icterus, and limb edema, typical of granulocytic equine ehrlichiosis, within 1 week.

Animals↗

LU103793 (NSC D-669356): a synthetic peptide that interacts with microtubules and inhibits mitosis.

LU103793 (NSC D-669356) is a new synthetic derivative of Dolastatin 15, an antiproliferative compound which was isolated from the mollusk Dolabella auricularia. Like Dolastatin 15, LU103793 is highly cytotoxic in vitro (IC50 = 0.1 nM). To investigate the mechanism of action of LU103793, we used a combination of biochemical and cellular methods. Turbidity assays with bovine brain microtubules demonstrated that LU103793 inhibits microtubule polymerization in a concentration-dependent manner (IC50 = 7 microM). Treatment with this compound also induced depolymerization of preassembled microtubules. Cell cycle analysis of tumor cell lines treated with LU103793 indicated a block in the G2-M phase. At the cellular level, it induced depolymerization of microtubules in interphase cells and development of abnormal spindles and chromosome distribution in mitotic cells. Although these effects are very similar to the cellular alterations caused by vinblastine, LU103793 does not inhibit vinblastine binding to unpolymerized tubulin in vitro. Our results suggest that LU103793 exerts its cytotoxic activity primarily through disruption of microtubule organization.

Adenocarcinoma↗

The role of the physician in effecting change in hospital charge for radical prostatectomy.

BACKGROUND: Continuing effort is being made to provide the best medical care in a cost-effective manner, requiring an evaluation of factors that control charges. The number of cases of carcinoma of the prostate gland and the number of radical retropubic prostatectomies performed have increased in recent years, with an estimate of several hundred million dollars being spent annually on this procedure in the United States of America. Because physicians are reported to effect the majority of charges for a hospitalization, this study examines the influence of notification of the physician of hospital charges on the overall hospital charges for radical retropubic prostatectomy. STUDY DESIGN: Total hospital charge and duration per hospitalization were determined for all patients having radical prostatectomies performed at five community hospitals in Richmond, VA, between January 1991 and December 1993. Patients included 625 males diagnosed with carcinoma of the prostate gland undergoing radical prostatectomy by one of 20 urologists from several different private practice groups. Halfway into the time period studied, physicians were notified of data collection and of factors that seemed to have a role in hospital charges. Total hospital charges before and after physician notification were measured to determine whether or not physicians could effect hospital charges. RESULTS: Overall, hospital charges decreased significantly after notification of physicians in the study. The decline in total charges continued throughout the follow-up period. Duration of hospitalization decreased throughout the entire study period, while total charge per hospital day increased. CONCLUSIONS: Physician awareness of hospital charges for operative procedures and accompanying hospitalizations may influence the overall decrease in charges.

Adult↗

Impact of physician awareness on hospital charges for radical retropubic prostatectomy.

PURPOSE: We determine if physician awareness of hospital costs for radical retropubic prostatectomy affects physician practice patterns. MATERIALS AND METHODS: We reviewed 256 consecutive radical retropubic prostatectomies performed by 14 urologists during 4 years at a community hospital. After 2 years the physicians were provided information on factors that may decrease charges. RESULTS: Charges decreased significantly following intervention, from +f417,134 within the initial 2 years to +f413,826 within the last 2 years (p < 0.005). Significant decreases were noted for length of stay, need for intensive care, operating time and blood loss. CONCLUSIONS: Traditional methods of physician education can impact practice patterns to decrease hospital charges for radical retropubic prostatectomy.

Adult↗

Evidence that palmitic acid is absorbed as sn-2 monoacylglycerol from human milk by breast-fed infants.

Milk fatty acids consist of about 20-25% palmitic acid (16:0), with about 70% of 16:0 esterified to the sn-2 position of the milk triacylglycerols. Hydrolysis of dietary triacylglycerols by endogeneous lipases produces sn-2 monoacylglycerols and free fatty acids, which are absorbed, reesterified, and then secreted into plasma. Unesterified 16:0 is not well absorbed and readily forms soaps with calcium in the intestine. The positioning of 16:0 at the sn-2 position of milk triacylglycerols could explain the high coefficient of absorption of milk fat. However, the milk lipase, bile salt-stimulated lipase, has been suggested to complete the hydrolysis of milk fat to free fatty acids and glycerol. These studies determined whether 16:0 is absorbed from human milk as sn-2 monopalmitin by comparison of the plasma triacylglycerol total and sn-2 position fatty acid composition between breast-fed and formula-fed term gestation infants. The human milk and formula had 21.0 and 22.3% of 16:0, respectively, with 54.2 and 4.8% 16:0 in the fatty acids esterified to the 2 position. The plasma triacylglycerol total fatty acids had 26.0 +/- 0.6 and 26.2 +/- 0.6% of 16:0, and the sn-2 position fatty acids had 23.3 +/- 3.3 and 7.4 +/- 0.7% of 16:0 in the three-month-old exclusively breast-fed (n = 17) and formula-fed (n = 18) infants, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Feeding↗

Development of visual acuity in relation to plasma and erythrocyte omega-6 and omega-3 fatty acids in healthy term gestation infants.

The development of preferential looking acuity was studied prospectively to 3 mo of age in exclusively breast-fed and formula-fed term gestation infants. The formula contained (% of total fatty acids) 17.9% linoleic acid (18:2 omega-6) and 2.1% alpha-linolenic acid (18:3 omega-3) but no docosahexaenoic acid (22:6 omega-3) or arachidonic acid (20:4 omega-6). The breast milk contained (mean +/- SEM) 13.4 +/- 0.8% 18:2 omega-6, 1.5 +/- 0.1% 18:3 omega-3, 0.51 +/- 0.03% 20:4 omega-6, and 0.22 +/- 0.02% 22:6 omega-3. Preferential looking acuity, assessed by the acuity-card procedure, and plasma phospholipid and erythrocyte phosphatidylcholine and phosphatidylethanolamine fatty acids were determined at 14 d and 3 mo of age. There were no significant differences in acuity at 14 d or 3 mo, despite substantial differences in erythrocyte and plasma lipid 22:6 omega-3. Visual acuity was [mean (cycles/degree) +/- SD (octaves)] 3.93 +/- 0.54 and 4.77 +/- 0.48 and erythrocyte phosphatidylethanolamine %22:6 omega-3 was (mean +/- SE) 7.6 +/- 0.5 and 4.0 +/- 0.2 in the 3-mo-old breast-fed and formula-fed infants, respectively. These studies show that feeding formula containing 2.1% 18:3 omega-3 (approximately 1.0% energy) results in development of visual acuity similar to breast-feeding in term infants to > or = 3 mo of age.

Breast Feeding↗

The UL45 gene product is required for herpes simplex virus type 1 glycoprotein B-induced fusion.

Herpes simplex virus type 1 (HSV-1) syncytial (syn) mutants cause formation of giant polykaryocytes and have been utilized to identify genes promoting or suppressing cell fusion. We previously described an HSV-1 recombinant, F1 (J.L. Goodman, M. L. Cook, F. Sederati, K. Izumi, and J. G. Stevens, J. Virol. 63:1153-1161, 1989), which has unique virulence properties and a syn mutation in the carboxy terminus of glycoprotein B (gB). We attempted to replace this single-base-pair syn mutation through cotransfection with a 379-bp PCR-generated fragment of wild-type gB. The nonsyncytial viruses isolated were shown by DNA sequencing not to have acquired the expected wild-type gB sequence. Instead, they had lost their cell-cell fusion properties because of alterations mapping to the UL45 gene. The mutant UL45 gene is one nonsyncytial derivative of F1, A4B, was found to have a deletion of a C at UL45 nucleotide 230, resulting in a predicted frame shift and termination at 92 rather than 172 amino acids. Northern (RNA) analysis showed that the mutant UL45 gene was normally transcribed. However, Western immunoblotting showed no detectable UL45 gene product from A4B or from another similarly isolated nonsyncytial F1 derivative, A61B, while another such virus, 1ACSS, expressed reduced amounts of UL45. When A4B was cotransfected with the wild-type UL45 gene, restoration of UL45 expression correlated with restoration of syncytium formation. Conversely, cloned DNA fragments containing the mutant A4B UL45 gene transferred the loss of cell-cell fusion to other gB syn mutants, rendering them UL45 negative and nonsyncytial. We conclude that normal UL45 expression is required to allow cell fusion induced by gB syn mutants and that the nonessential UL45 protein may play an important role as a mediator of fusion events during HSV-1 infection.

Amino Acid Sequence↗

A combination of human cytomegalovirus (HCMV)-specific murine monoclonal antibodies exhibits synergistic antiviral activity in vitro.

A combination of HCMV-specific monoclonal antibodies (MAbs) reactive with glycoproteins in gcI complexes which exhibit synergistic antiviral activity in vitro is described. MAbs directed against different structural and biological properties of HCMV have been selected to increase the antiviral activity against all possible strains, and to reduce the likelihood that resistant strains will emerge with prolonged exposure. Furthermore, in vitro analysis demonstrates that certain of the MAbs in the combination augment the virus-neutralizing activity of other component antibodies, thereby decreasing the amount of total antibody protein required to inhibit HCMV infection. Certain MAbs have been selected to inactivate extracellular virus during the early phase of HCMV infection, whereas others have been selected to prevent its spread once cells have been infected. These data suggest that a MAb cocktail may be useful for prophylaxis and treatment of patients at risk of life-threatening HCMV infections.

Antibodies, Monoclonal↗

High-pressure, high-temperature bioreactor for comparing effects of hyperbaric and hydrostatic pressure on bacterial growth.

We describe a high-pressure reactor system suitable for simultaneous hyperbaric and hydrostatic pressurization of bacterial cultures at elevated temperatures. For the deep-sea thermophile ES4, the growth rate at 500 atm (1 atm = 101.29 kPa) and 95 degrees C under hydrostatic pressure was ca. three times the growth rate under hyperbaric pressure and ca. 40% higher than the growth rate at 35 atm.

Bacteria↗

The human antibody response to streptococcal C5a peptidase.

An ELISA was developed to measure antibody, both IgG and IgA, against the streptococcal C5a peptidase (SCP), in human sera and saliva. Generally, sera and saliva from young, uninfected children lacked antibody to SCP. In contrast, most sera and saliva specimens from healthy adults had measurable levels of anti-SCP IgG and SCP-specific secretory IgA (anti-SCP sIgA). Paired acute and convalescent sera from patients with streptococcal pharyngitis possessed significantly higher levels of anti-SCP IgG than did sera from healthy individuals. Sera containing high concentrations of anti-SCP immunoglobulin were capable of neutralizing SCP activity. A survey of healthy adults and children also showed that the latter were significantly less likely to have anti-SCP sIgA in their saliva. Detection of this antibody in greater than 90% of the saliva specimens obtained from children who had recently experienced streptococcal pharyngitis demonstrated that children can produce a secretory response. This is thought to be the first report of a secretory IgA response in humans to a somatic antigen of Streptococcus pyogenes.

Acute Disease↗

Effects of hyperbaric pressure on a deep-sea archaebacterium in stainless steel and glass-lined vessels.

The effects of hyperbaric helium pressures on the growth and metabolism of the deep-sea isolate ES4 were investigated. In a stainless steel reactor, cell growth was completely inhibited but metabolic gas production was observed. From 85 to 100 degrees C, CO(2) production proceeded two to three times faster at 500 atm (1 atm = 101.29 kPa) than at 8 atm. At 105 degrees C, no CO(2) was produced until the pressure was increased to 500 atm. Hydrogen and H(2)S were also produced biotically but were not quantifiable at pressures above 8 atm because of the high concentration of helium. In a glass-lined vessel, growth occurred but the growth rate was not accelerated by pressure. In most cases at temperatures below 100 degrees C, the growth rate was lower at elevated pressures; at 100 degrees C, the growth rates at 8, 250, and 500 atm were nearly identical. Unlike in the stainless steel vessel, CO(2) production was exponential during growth and continued for only a short time after growth. In addition, relatively little H(2) was produced in the glass-lined vessel, and there was no growth or gas production at 105 degrees C at any pressure. The behavior of ES4 as a function of temperature and pressure was thus very sensitive to the experimental conditions.

Journal Article↗

Management of benign ureteral structures: open surgical repair or endoscopic dilation?

We reviewed 20 cases of ureteral strictures, 15 of which were secondary to ureteral trauma. Of the patients 6 were managed initially by open repair and 14 underwent endoscopic manipulation. All 6 open repairs were successful, compared to 9 of the 14 patients who underwent endoscopic dilation of the ureteral stricture. Of the 5 failures 3 were due to the inability to cannulate the strictured ureter with a guide wire and 2 failed to respond to balloon dilation. Of these 5 patients 4 were treated successfully by an open operation. There were no serious intraoperative or postoperative complications. The average hospitalization was less for the endoscopic group (2.1 days) compared to the open surgical group (8.3 days). Followup ranged from 6 to 48 months.

Adult↗

Pressure and Temperature Effects on Growth and Methane Production of the Extreme Thermophile Methanococcus jannaschii.

The marine archaebacterium Methanococcus jannaschii was studied at high temperatures and hyperbaric pressures of helium to investigate the effect of pressure on the behavior of a deep-sea thermophile. Methanogenesis and growth (as measured by protein production) at both 86 and 90 degrees C were accelerated by pressure up to 750 atm (1 atm = 101.29kPa), but growth was not observed above 90 degrees C at either 7.8 or 250 atm. However, growth and methanogenesis were uncoupled above 90 degrees C, and the high-temperature limit for methanogenesis was increased by pressure. Substantial methane formation was evident at 98 degrees C and 250 atm, whereas no methane formation was observed at 94 degrees C and 7.8 atm. In contrast, when argon was substituted for helium as the pressurizing gas at 250 atm, no methane was produced at 86 degrees C. Methanogenesis was also suppressed at 86 degrees C and 250 atm when the culture was pressurized with a 4:1 mix of H(2) and CO(2), although limited methanogenesis did occur when the culture was pressurized with H(2).

Journal Article↗

Antibody inhibition of HeLa cell invasion by Yersinia enterocolitica.

Antisera were prepared in rabbits against formalized and heat-killed bacteria of Yersinia enterocolitica serotype O:5,27 and against formalized bacteria of serotype O:8. Both strains used for immunization demonstrated adhesion to and invasion of HeLa cells. Coating of the bacteria with antibody did not greatly alter adhesion (i.e., extracellular attachment) to HeLa cells; however, antibody against formalized bacteria of both serotypes inhibited HeLa cell invasion by the homologous and heterologous strains. The Fab fragments from purified immunoglobulins also demonstrated cross-reacting inhibition of HeLa cell invasion. Antibody against heat-killed bacteria of serotype O:5,27 had no inhibitory activity. Adsorption of the antiserum against formalized bacteria of serotype O:5,27 with lipopolysaccharide from the homologous strain removed anti-lipopolysaccharide antibody but did not remove the inhibitory activity. The antiserum against formalized bacteria of serotype O:8 showed no antibody against lipopolysaccharide from serotype O:5,27 and no agglutinins against heat-killed bacteria of this strain. From these results, it is tentatively suggested that protein structures are important in mediating epithelial cell invasion by Y. enterocolitica.

Adsorption↗