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Biomedical subjects

J Davis

Publications and source records attributed to J Davis.

At least 613 records · Page 34Linked to original sources
PubMedDate not supplied

Dysarthria of motor neuron disease: longitudinal measures of segmental durations.

Motor neuron disease encompasses a group of terminal, demyelinating diseases affecting upper- and lower-motor neurons and producing muscular weakness resulting in a flaccid, spastic, or spastic-flaccid dysarthria of speech. The present study presents measurements of the temporal-acoustic characteristics of dysarthria in three subjects with Motor Neuron Disease over a two-year recording period. Changes seen over the course of the disease varied by type of motor neuron disease, though all types demonstrated some degree of neutralization of the prevocalic VOT, target vowel duration, and postvocalic closure duration. These changes are discussed with relation to physical manifestation and progression of the disease.

Aged↗
PubMedDate not supplied

Impact of positive preoperative surveillance blood cultures from chronic indwelling catheters in cadaveric intestinal transplant recipients.

Recurrent bloodstream infections are a common indication for intestinal transplantation (ITx). Often, clinical symptoms may be absent in the setting of bacteremia, especially in patients with chronic liver disease. This study investigated the incidence and impact of positive blood cultures (BCx) obtained from central venous catheters used for total parenteral nutrition (TPN) in asymptomatic patients immediately prior to cadaveric ITx. Of 13 consecutive patients transplanted between November 2003 and November 2004, 12 underwent preoperative surveillance BCx with four positives (33%). Isolates included Staphylococcus epidermidis (n = 2), methicillin-resistant Staphylococcus aureus, and Citrobacter freundii. All four patients with positive BCx displayed liver dysfunction at the time of transplant (> or = grade 2 fibrosis, total bilirubin >8.0 g/dL), three of whom were inpatients. In contrast, only three of eight nonbacteremic patients showed liver disease of comparable severity. Liver dysfunction and inpatient status at the time of transplant appear to predict positive blood cultures. Postoperative length of stay and time on the ventilator were significantly longer among bacteremic as compared with nonbacteremic patients, but there were no differences in intraoperative blood use, time to total parenteral nutrition independence, or operative time between bacteremic and nonbacteremic patients. Our study showed that occult bacteremia in asymptomatic pre-intestinal transplant patients was not uncommon and may increase postoperative morbidity. Preemptive removal of long-term central venous catheters should be considered prior to ITx.

Cadaver↗
PubMedDate not supplied

Differential expression of transforming growth factor-beta 1 and transforming growth factor-beta receptors in myometrium of women with failed induction of labor, no labor, and preterm labor.

OBJECTIVE: Comparative analysis of transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta receptor type I and type II messenger RNA (mRNA) and protein expression in myometrium of women who had unsuccessful labor induction, with those without labor or in preterm labor complicated by chorioamnionitis. METHODS: Small segments of myometrium were collected from women who were undergoing cesarean delivery for unsuccessful labor induction (n = 5), elective cesarean without labor (n = 5), or cesarean delivery for complications related to preterm labor and chorioamnionitis (n = 5). Total RNA was isolated from these tissues and subjected to competitive quantitative reverse-transcription-polymerase chain reaction (Q-RT-PCR) to determine the level of TGF-beta 1, and TGF-beta type I and type II receptor mRNA expression. Tissue sections were prepared from paraffin-embedded specimens and immunostained for TGF-beta 1 and receptor proteins using specific polycolonal antibodies. The data were analyzed by impaired Student t test and Kruskal-Wallis analysis of variance. RESULTS: Myometrium from women who had unsuccessful labor induction expressed higher levels of TGF-beta 1 mRNA (2.21 +/- 0.28 x 10(6) copies/microgram of total cellular RNA) than those with preterm labor (4.53 +/- 0.2 x 10(5) copies), or without labor [3.13 +/- 2.6 x 10(4) copies (P < .05)]. The level of TGF-beta type I receptor mRNA expression did not vary; however, type II receptor expression was significantly lower in myometrium from preterm labor (1.36 +/- 0.36 x 10(5) copies) compared with those from unsuccessful labor induction (3.42 +/- 0.42 x 10(6) copies) or without labor (9.65 +/- 3.2 x 10(5) copies). Immunoreactive TGF-beta 1 and TGF-beta receptor proteins were present in all myometrial tissues, and their intensity reflected that of the mRNA expression in these tissues. CONCLUSION: TGF-beta 1 and TGF-beta type II receptors are expressed differently in myometrium of women who had unsuccessful labor induction compared with those without labor or with preterm labor complicated by chorioamnionitis. Because TGF-beta is a key regulator of tissue remodeling which is central to initiation of normal labor, alterations in TGF-beta and/or TGF-beta receptor expression may lead to changes in the outcome of labor, at least at the myometrial level.

Cesarean Section↗
PubMedDate not supplied

A novel approach to high-throughput quality control of parallel synthesis libraries.

Combinatorial chemistry is a powerful tool to enhance drug discovery efforts in the pharmaceutical industry. One type of combinatorial chemistry, parallel synthesis, is now widely used to prepare numerous compounds of structural diversity. A novel high-throughput method for quality control of parallel synthesis libraries has been developed. The method uses flow injection MS, for proof of structure and estimation of purity, and a novel direct injection CLND technique for quantitation of amount. Following the synthesis of a small molecule library, compounds analyzed using this technique were characterized by mass spectrometry, and an accurate concentration of the compound was assessed by CLND. Characterization of one compound is completed in 60 s, allowing for up to 1000 compounds to be analyzed in a single day. The data is summarized using pass/fail criteria using internally developed software.

Chemistry, Organic↗
PubMedDate not supplied

Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites.

A 12 amino-acid synthetic peptide (NANP)3 comprising the immunodominant epitope of Plasmodium falciparum circumsporozoite protein was conjugated to tetanus toxoid (TT), adjuvanted with aluminium hydroxide, and administered intramuscularly in three doses at monthly intervals to 35 healthy males as a malaria vaccine. No significant adverse reactions were noted, with mild soreness at the injection site the only common symptom. Seroconversions against NANP occurred in 53% and 71% of recipients of 100 or 160 micrograms, respectively, measured by enzyme-linked immunosorbent assay (ELISA). Most ELISA-positive sera reacted with sporozoites by indirect immunofluorescence (IFA). Three vaccinees with the highest ELISA and IFA titres and four unimmunized controls were challenged with P. falciparum sporozoites introduced via the bites of infective Anopheles mosquitoes. Blood stage parasites were detected in all controls by 10 days (mean 8.5 days, range 7-10). In contrast, the two vaccinees who became infected did not manifest parasitaemia until day 11 and the third vacinee showed neither parasites nor symptoms during the 29 day observation period. This first synthetic peptide parenteral vaccine against a communicable disease tested in man is safe and stimulates biologically active antibodies. These observations encourage the development of improved vaccine formulations which, by enhancing immunogenicity, may lead to practical vaccines to assist in the control of falciparum malaria.

Animals↗
PubMedDate not supplied

Bacterial sepsis secondary to platelet transfusion: an adverse effect of extended storage at room temperature.

In a 3-month period four episodes of bacterial sepsis related to contaminated random donor platelet concentrates were observed. Evaluation incriminated extended (5 or more days) platelet storage. To determine if platelets stored for longer periods were likely to have greater bacterial contamination, platelet concentrates were inoculated with bacteria and daily quantitative bacteriology was performed. In vitro studies using polyolefin bags indicated contamination could occur with a single organism of Staphylococcus epidermidis. By 72 hours, platelet concentrates contained from 10(3) to 10(8) organisms per 0.1 ml depending on the inoculum size. By 6 days all inoculated units contained 10(7) to 10(9) organisms per 0.1 ml.

Blood Preservation↗
PubMedDate not supplied

Bacterial contamination of bone marrow grafts intended for autologous and allogeneic bone marrow transplantation. Incidence and clinical significance.

In a series of 100 bone marrow harvests, the incidence of bacterial contamination of the bone marrow graft was 17 percent. Ex vivo manipulation of some of the grafts prior to infusion may have caused additional bacterial contamination. All isolated bacteria were common skin flora, and no serious sequelae were observed in the patients receiving the culture-positive bone marrow grafts. Samples of harvested bone marrows purposely contaminated with an isolate of Staphylococcus epidermidis demonstrated a bactericidal property that was maximal early after bone marrow collection. Bone marrow collection and ex vivo manipulation may result in considerable bacterial contamination. Procedures must be developed to assure that marrow collection and processing do not result in clinically significant contamination.

Bacteria↗
PubMedDate not supplied

Metabolism, pharmacokinetics and excretion of a potent tachykinin NK1 receptor antagonist (CP-122,721) in rat: characterization of a novel oxidative pathway.

The metabolism, pharmacokinetics and excretion of a potent and selective substance P receptor antagonist, (+)-(2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzlamino)-2-phenylpiperidine, CP-122,721, have been studied in rat following oral administration of a single dose of [14C]CP-122,721. Total recovery of the administered dose was 84.1+/-1.1% for male rat and 80.9+/-2.7% for female rat. Approximately 81% of the administered radioactivity recovered in urine and faeces were excreted in the first 72 h. Absorption of CP-122,721 was rapid in both male and female rat, as indicated by the rapid appearance of radioactivity in plasma. The plasma concentrations of total radioactivity were always much greater than unchanged drug, indicating early formation of metabolites. CP-122,721 t1/2 was 3.1 and 2.2 h for male and female rat, respectively. The plasma concentrations of CP-122,721 reached a peak of 941 and 476 ng ml-1 for male and female rat, respectively, at 0.5 h post-dose. Based on AUC0-tlast, only 1.5% of the circulating radioactivity was attributable to unchanged drug (average of male and female rats) and the balance, approximately 98.5% of the plasma radioactivity was due to metabolites. The major metabolic pathways of CP-122,721 were due to O-demethylation, aromatic hydroxylation and indirect glucuronidation. The minor metabolic pathways included aliphatic oxidation at the piperidine moiety and aliphatic oxidation at the benzylic position of the trifluoromethoxy anisole moiety. In addition, a novel oxidative metabolite resulting from ipso substitution by the oxygen atom and trifluoromethoxy elimination followed by glucuronide conjugation was also identified.

Administration, Oral↗
PubMedDate not supplied

Comparison of ADCC and NK activities of peripheral blood mononuclear cells from patients at risk for acquired immune deficiency syndrome (AIDS).

Numerous cellular immune defects have been described in patients with acquired immune deficiency syndrome (AIDS). These include anergy, reduced numbers of helper T cells, and decreased effectiveness of natural killer (NK) cells. In this study, we have measured the lytic activity of antibody-dependent cellular cytotoxic (K) cells using a recently described 51Cr release assay in patients clinically displaying lymphadenopathy syndrome (LAD). We then compared ADCC activity with NK activity, T helper/T suppressor ratios and NK cell number in these same patients. Our results indicate that a reduction of ADCC activity can occur in patients with LAD. In our study, patients that showed reduced ADCC activity also showed reduced NK cell function. Other individuals in this study had reduced NK function while ADCC values remained within the normal range. The degree of reversal of the T helper/T suppressor cell ratio was not a useful indicator of cellular immune function as measured by these assays in that individuals with very low ratios often had normal cytotoxic cell function while some patients with ratios in the normal range had decreased cytotoxicity. The percentage of NK cells as determined by HNK-1 monoclonal antibody also did not prove useful in defining potential cytotoxic activities.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Epstein-Barr virus and chronic lymphadenomegaly in male homosexuals with acquired immunodeficiency syndrome (AIDS).

Male homosexuals at risk for developing AIDS frequently exhibit chronic lymphadenomegaly (LAD). They are at high risk for developing malignant B cell lymphomas. A study of Epstein-Barr virus (EBV) revealed marked abnormalities in these patients. One hundred percent of the patients were seropositive. The patients with most severe acquired immune deficiency disorders manifested a decreased number of circulating B cells with EBV receptors and decreased lymphocyte transformation. Patients often showed defective memory T cell cytotoxic responses to autologous EBV infection in vitro. Three of five lymph node specimens contain significant EBV genome copies to suggest a significant etiologic role. In addition, a Burkitt-like lymphoma carried EBV genome. Although all of the men were seropositive for EBV, reactivation patterns were not as common as anticipated. Given the presence of EBV genome in the lymph nodes of the patients who lack anti-early antigen (EA) antibodies indicative of reactivation, we suggest that reliance on serology to indicate EBV involvement is insufficient for assessing the patient. The detection of a t(8;14) transposition in the monoclonal mu kappa Burkitt-like lymphoma containing EBV genome supports the view that cytogenetic transposition is a mechanism in lymphomagenesis.

Acquired Immunodeficiency Syndrome↗