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Biomedical subjects

W Smith

Publications and source records attributed to W Smith.

At least 19 recordsLinked to original sources

Measurement of the proportion of free to total prostate-specific antigen improves diagnostic performance of prostate-specific antigen in the diagnostic gray zone of total prostate-specific antigen.

OBJECTIVES: This study examined the clinical significance of non-complexed (free) prostate-specific antigen (PSA) in the differential diagnosis of prostate cancer with an emphasis on patients with total PSA values between 4.0 and 10.0 ng/mL (the diagnostic gray zone). METHODS: Serum samples were obtained from three specimen banks. Patient samples consisted of 55 untreated histologically confirmed primary cancer, 62 men with untreated benign prostatic disease histologically confirmed by 6 negative sextant biopsies, and 64 asymptomatic healthy male controls with normal digital rectal examinations and PSA values less than 4.0 ng/mL. All patients were between the ages of 50 and 75 years. Total PSA levels were determined using the PA immunoassay performed on the TOSOH AIA-1200 automated immunoassay instrument. Free PSA levels were determined using a monoclonal-polyclonal antibody sandwich radioimmunoassay. The proportion of free to total PSA was calculated by dividing the patient's free PSA value by the total PSA value. RESULTS: When all subjects were included, both total PSA and the proportion of free to total PSA significantly differentiated between patients with prostate cancer and patients with benign histologic conditions (P < 0.0001). However, in men with total PSA values between 4.0 and 10.0 ng/mL, the proportion of free to total PSA significantly differentiated between patients with benign and malignant histologic conditions (P = 0.0004), whereas the total PSA did not (P = 0.13). Among this subgroup of patients, the analysis of sensitivity and specificity showed that the proportion of free to total PSA had a clearly higher specificity compared with that of the total PSA at the same level of sensitivity. CONCLUSIONS: Measurement of the free PSA level in a patient's serum and calculation of the proportion of free to total PSA enhances the ability to distinguish benign histologic conditions from cancer while retaining high sensitivity for detecting cancer in men who present with total PSA levels between 4.0 and 10.0 ng/mL. A large-scale population-based study is currently in progress to confirm this preliminary finding.

Aged

Effect of a leukotriene B4 receptor antagonist SC-53228 on ozone-induced airway hyperresponsiveness and inflammation in dogs.

The importance of the potent neutrophil chemoattractant leukotriene (LT)B4 in causing ozone-induced bronchoconstriction, airway inflammation, and airway hyperresponsiveness in dogs was studied using the LTB4-receptor antagonist SC-53228. Seven dogs from random sources were studied three times, at least 2 wk apart. On each occasion, acetylcholine (Ach) airway responsiveness was measured before and 1 h after ozone (3 ppm, 30 min) or dry air inhalation, followed by a bronchoalveolar lavage (BAL). On the first day, dogs were treated with SC-53228 (0.4 mg/kg intravenously) followed by a continuous intravenous infusion of 1.2 mg/kg/h before ozone inhalation. On the other two days, diluent was infused followed by ozone or dry air inhalation. Cell counts were measured in BAL and cell activation was measured by spontaneous and by phorbol myristate acetate-stimulated (PMA) (2.4 mumol/L) oxygen radical release, measured from washed BAL cells (4 x 10(6) cells) by lucigenin-enhanced chemiluminescence. Ozone inhalation caused bronchoconstriction and airway hyperresponsiveness. SC-53228 inhibited the ozone-induced airway hyperresponsiveness (p = 0.006), but not the bronchoconstriction. Spontaneous (p = 0.004) and PMA-stimulated (p = 0.04) lucigenin-enhanced chemiluminescence were increased after ozone inhalation. The ozone-induced increases in PMA-stimulated chemiluminescence were significantly attenuated by treatment with SC-53228 (p = 0.04). These results suggest that LTB4 is involved in the pathogenesis of ozone-induced airway hyperresponsiveness, possibly through activation of airway inflammatory cell.

Acetylcholine

N omega-nitro-L-arginine methyl ester reduces the incidence of IDDM in BB/E rats.

Evidence that nitric oxide (NO) is involved in cytokine-mediated islet beta-cell dysfunction and destruction in vitro has led to the hypothesis that increased production of NO may contribute to the pathogenesis of insulin-dependent diabetes mellitus (IDDM). This study demonstrates that oral administration of N omega-nitro-L-arginine methyl ester (an inhibitor of NO synthase) from 30 to 150 days of age significantly reduced (P < 0.05) the incidence of IDDM in diabetes-prone BB/E rats. This supports the idea that NO plays a significant role in the pathogenesis of IDDM in this animal model.

Administration, Oral

Indolicidin, a novel bactericidal tridecapeptide amide from neutrophils.

A potent and structurally novel antimicrobial peptide was purified from the cytoplasmic granules of bovine neutrophils. Suspensions of Staphylococcus aureus and Escherichia coli were virtually sterilized by the peptide at a concentration of 10 micrograms/ml. The peptide was found to be comprised of 13 amino acids, 5 of which were tryptophan residues, and the carboxyl-terminal arginine was carboxamidated. The primary structure of the peptide, which we have named indolicidin, is H-Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-NH2. The mole percent of tryptophan in indolicidin is the highest observed among known protein sequences. The multiple tryptophan residues presumably play an important role in the function of this unique antibiotic peptide.

Amino Acid Sequence

Comparison and sensitivity to change of self-report scales to assess difficulty, dissatisfaction, and pain in performing activities of daily living over one and five years in rheumatoid arthritis.

We analyzed the longitudinal sensitivity to change of three self-report activities of daily living (ADL) scales over 1 and 5 years in 982 patients with rheumatoid arthritis (RA) from 15 private practices. Over 1 year, the ADL difficulty status worsened in 28.3% of the patients, remained the same in 50.2%, and improved in 21.5%. Over 5 years, 41.3% worsened, 38.8% stayed the same, and 19.9% were improved. Similar percentages for 1- and 5-year changes were found for the ADL dissatisfaction and pain scales. The effect sizes for change over 1 and 5 years for the ADL difficulty, dissatisfaction, and pain scales were--(-)0.05, 0.01, and -0.02, and -0.28, -0.20, and -0.14, respectively, indicating small to moderate declines. These data indicate that the three ADL scales are sensitive to change in status, and ADL change status scores after 1 and 5 years were significantly correlated with each other (r = 0.49-0.68, all p < 0.001). Monitoring of these three constructs may be helpful in the longitudinal evaluation of some patients with RA.

Activities of Daily Living

Solution structure of a synthetic peptide corresponding to a receptor binding region of FSH (hFSH-beta 33-53).

The receptor binding surface of human follicle-stimulating hormone (hFSH) is mimicked by synthetic peptides corresponding to the hFSH-beta chain amino acid sequences 33-53 [Santa-Coloma, T. A., Dattatreyamurty, D., and Reichert, L. E., Jr. (1990), Biochemistry 29, 1194-1200], 81-95 [Santa-Coloma, T. A., Reichert, L. E., Jr. (1990), J. Biol. Chem. 265, 5037-5042], and the combined sequence (33-53)-(81-95) [Santa-Coloma, T. A., Crabb, J. W., and Reichert, L. E., Jr. (1991), Mol. Cell. Endocrinol. 78, 197-204]. These peptides have been shown to inhibit binding of hFSH to its receptor. Circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy were used to determine the structure of the first peptide in this series, the 21 amino acid peptide hFSH-beta-(33-53), H2N-YTRDLVYKDPARPKIQKTCTF-COOH. Analysis of CD data indicated the presence of approximately equal amounts of antiparallel beta-pleated sheet, turns including a beta-turn, "other" structures, and a small amount of alpha-helix. The major characteristics of the structure were found to be relatively stable at acidic pH and the predominant effect of increased solvent polarity was a small increase in alpha-helical content. One- and two-dimensional NMR techniques were used to obtain full proton and carbon signal assignments in aqueous solution at pH 3.1. Analysis of NMR results confirmed the presence of the structural features revealed by CD analysis and provided a detailed picture of the secondary structural elements and global folding pattern in hFSH-beta-(33-53). These features included an antiparallel beta-sheet (residues 38-51 and 46-48), turns within residues 41-46, and 50-52 (a beta-turn) and a small N-terminal helical region comprised of amino acids 34-36. One of the turns is facilitated by prolines 42 and 45. Proline-45 was constrained to the trans conformation, whereas proline-42 favored the trans conformer (approximately 70%) over the cis (approximately 30%). Two resonances were observed for the single alanine residue (A-43) sequentially proximal to P-42, but the rest of the structure was minimally affected by the isomerization at proline-42. The major population of molecules, containing trans-42 and trans-45 prolines, presented 120 NOEs. Distance geometry calculations with 140 distance constraints and energy minimization refinements were used to derive a moderately well-defined model of the peptide's structure.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence

Lingual infarction: a review of the literature.

Lingual infarction, although a very rare entity has been reported in 16 cases since 1961. The goal of this article is to alert the physician to the symptoms of tongue claudication to prevent the morbid effects of tongue infarction and blindness due to cranial arteritis. A discussion of the disease and the differential diagnosis is included.

Aged

Young maternal age and parity. Influences on pregnancy outcome.

The influence of very young maternal age and parity on pregnancy outcome was examined in a cohort of nearly 900 adolescents and mature women from Camden, New Jersey. Young primigravid primiparas (aged 12 to 15 years) were compared with mature primigravid primiparas (18 to 29 years). Young multiparas (19 years or younger, with a first pregnancy at the age of 12 to 15 years) were compared with mature, multiparas (19 to 29 years old, with a first pregnancy at 18 years or older). After controlling for confounding factors, young primiparas were found to have a modest increase in preterm delivery, which was not statistically significant. However, low gynecologic age contributed disproportionately to the risk of preterm delivery in this group, with risk decreasing with each year from menarche (Cox's proportional hazard, 0.80; 95% confidence interval [CI], 0.68 to 0.94). Among multiparas, there were several statistical interactions associated with increased risk of small-for-gestational-age infants, including interactions between young age and low pre-pregnancy body mass (adjusted odds ratio [AOR], 5.74; 95% CI, 2.18 to 15.08), young age and a prior low-birth-weight infant (AOR, 10.58; 95% CI, 3.89 to 28.77), and young age and a prior preterm delivery (AOR, 5.52; 95% CI, 2.04 to 14.98). Thus, while chronologic age per se may not be a good predictor of pregnancy outcome, adolescents remain a high-risk group because of factors that are more common among them (e.g., biologic immaturity, inadequate prenatal care, poverty, minority status, low prepregnancy weight) and because factors associated with an early adolescent pregnancy, such as low gynecologic age, may continue to influence the outcome of subsequent pregnancies.

Adolescent

Immunoglobulins secreted by a hybrid-hybridoma: analysis of chain assemblies.

In addition to the bispecific antibody, the hybrid-hybridoma 28.19.8 secretes antibodies monospecific for carcinoembryonic antigen (CEA) and antibodies monospecific for vinca alkaloids. By exhaustive affinity purification, the immunoglobulins isolated by Protein A chromatography from ascitic fluid have been fractionated into four populations, three of which are immunoreactive. Studies on these fractions by FPLC, SDS-PAGE, and a variety of ELISAs have shown that seven of the ten possible combinations of heavy and light chains exist as immunoreactive forms. The results suggest that the other three inactive combinations are also secreted by the hybrid-hybridoma.

Animals

First-time coronary artery bypass grafting: the anaesthetist as a risk factor.

We have investigated the contribution of the anaesthetist and surgeon to outcome after 1301 consecutive coronary artery bypass grafting operations (first operation). The mean + 1 SD aspartate amino transferase concentration on the day after surgery (AST-D1) was 134 u litre-1 (or, after logarithmic transformation, 94 u litre-1). Twenty patients were selected at random from each of three groups having AST-D1 less than 100 u litre-1, 100-134 u litre-1 or greater than 134 u litre-1; positive ECG diagnoses of perioperative myocardial infarction were significantly more frequent with AST-D1 values greater than 100 u litre-1 than with smaller values, but no more frequent with AST-D1 greater than 134 u litre-1. Because several deaths occurred before AST-D1 could be measured, an "adverse outcome" was defined as either hospital death or AST-D1 greater than 100 u litre-1. Univariate analysis implicated both anaesthetist and surgeon as significant predictors of adverse outcome but, after allowing for 12 patient-related factors, only cardiopulmonary bypass time (or ischaemic cross-clamp time) (P less than 0.01) and anaesthetist (P = 0.05) were associated significantly with outcome.

Aged

Corneal storage medium preservation with defensins.

We used a synthetic defensin (rabbit neutrophil peptide-1; NP-1) as a microbicide in a corneal storage medium, Optisol without antimicrobial compounds. We established growth curves in Optisol for Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Each organism was evaluated separately at 4 degrees C, 23 degrees C, and 37 degrees C in Optisol with NP-1 at each of four different concentrations including 1, 10, 100, and 200 micrograms/ml. When the three organisms were evaluated in Optisol containing NP-1, we found that a concentration of 200 micrograms/ml of NP-1 successfully killed 99.9% (the limits of our assay) of all three organisms at all temperatures tested. We conclude that NP-1 exhibits promise as a nonantibiotic preservative agent in corneal storage media, since it was effective in killing organisms at all temperatures, including 4 degrees C.

Antifungal Agents

Hematologic and bone marrow changes after short- and long-term administration of two recombinant bovine granulocyte colony-stimulating factors.

Colony-stimulating factors are a category of glycoproteins that are instrumental in the regulation of hematopoiesis and inflammation. This investigation documented the clinical bone marrow and peripheral blood responses to short-term and long-term administration of a recombinant bovine granulocyte colony-stimulating factor (rb-GCSF) and an analog, where the cysteine at position 17 was substituted with a serine (rb-GCSF ser17). The colony-stimulating factors produced the expected changes in the hematologic findings of the bovine subjects in the study, and there was a cell-specific response to the compounds. The sustained neutrophilia in the long-term study indicates that the bovine species can tolerate the administration of recombinant forms of bovine GCSF for extended periods of time without detectable adverse side effects. The neutrophils from the short-term study revealed no apparent fluctuation, either as enhanced or reduced capability to reduce nitro blue tetrazolium as compared to pretreatment neutrophils. The administration of both recombinant forms of GCSF produced large increases in the bone marrow myeloid:erythroid (M:E) ratio concomitantly with the neutrophilias. This is the first preliminary report documenting the bone marrow response of cattle to the native and recombinant (rb-GCSF ser17) forms of bovine GCSF.

Animals

Characterization of three T-lymphoid cell lines with distinct sensitivities to deoxyadenosine plus deoxycoformycin.

Three established human T-cell lines, HPB-MLT, HPB-ALL and PEER, were characterized and tested for their sensitivity to deoxyadenosine (dAdo) plus deoxycoformycin (dCoF). Phenotypic characterizations showed that all three cell lines had receptors for peanut agglutinin (PNA) and soybean agglutinin (SBA) while HPB-MLT and HPB-ALL, but not PEER, expressed the cortical thymocyte-specific marker, CD1. The majority of HPB-MLT cells (88%) expressed only CD4 but not CD8 antigen while most HPB-ALL cells (81%) co-expressed CD8 and CD4 antigens. PEER cells were negative for both CD8 and CD4. These three T cell lines showed differential sensitivity to dAdo plus dCoF in consequent tests. dAdo or dAdo plus dCoF (1 microM) had no effect on the growth, or DNA and RNA synthesis of HPB-MLT cells while the combination of dAdo and dCoF partially inhibited cellular growth and DNA and RNA synthesis of HPB-ALL cells. Further, the growth and DNA and RNA synthesis of PEER cells were strongly inhibited by the combination of dAdo and dCoF. This high sensitivity to dAdo plus dCoF reflected an immature phenotype of PEER cells despite its expression of CD3. Flow cytometric analysis of PEER cells demonstrated disappearance of the G2/M phase cells from the cell cycle after treatment with dAdo plus dCoF. Measurements of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities in all three cell lines, however, did not establish correlations between purine metabolizing enzyme activities and the differential sensitivities to dAdo plus dCoF. In sum, we report here three T-cell lines of different phenotypes that displayed significantly different sensitivities to dAdo plus dCoF which may facilitate investigations on the mechanisms of ADA deficiency.

Adenosine Deaminase

Biologic, foster, and adoptive parents: care givers of children exposed perinatally to human immunodeficiency virus in the United States. The Pediatric Spectrum of Disease Clinical Consortium.

Children born to human immunodeficiency virus (HIV)-infected mothers often do not live with a biologic parent because of drug use, illness, or death of the mother. Public health officials need to know the number and proportion of children who will require care by someone other than a biologic parent (alternative care giver). The Pediatric Spectrum of Disease project, conducted in six different geographic regions in the United States, assesses issues specific to HIV in children. Among the information being collected in this study are data regarding the primary care giver. Of 1683 children born to HIV-infected mothers and enrolled through 1990, 55% (937) were living with a biologic parent, 10% (169) with another relative, 28% (455) were in foster care, 3% (55) had been adopted, and 4% (67) lived in group settings or with other care givers. In all locations and for all racial/ethnic groups, children of mothers who used intravenous drugs were more likely to be living with an alternative care giver than were children of mothers who had not used intravenous drugs (odds ratio 4.15). However, there were striking variations by study location (odds ratio range 1.4 to 7.2). The data suggest that maternal drug use may be the most important factor determining whether a child lives with a biologic parent and that there are also regional differences in alternative care placement.

Adoption