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Biomedical subjects

J West

Publications and source records attributed to J West.

At least 91 records · Page 5Linked to original sources

Sympathomimetic preference and ethnicity in male felons.

A disproportionate number of Euro-American inmates given either an amphetamine- or cocaine-abuse diagnosis upon admission to prison were given a diagnosis of amphetamine abuse. A disproportionate number of African-American inmates were given a cocaine-abuse diagnosis. Of the 800 consecutively admitted inmates who were given one diagnosis or the other, 68% of the cocaine abusers, but only 4% of the amphetamine abusers, were African American.

Adult↗

Accessibility of selenomethionine proteins by total chemical synthesis: structural studies of human herpesvirus-8 MIP-II.

The determination of high resolution three-dimensional structures by X-ray crystallography or nuclear magnetic resonance (NMR) is a time-consuming process. Here we describe an approach to circumvent the cloning and expression of a recombinant protein as well as screening for heavy atom derivatives. The selenomethionine-modified chemokine macrophage inflammatory protein-II (MIP-II) from human herpesvirus-8 has been produced by total chemical synthesis, crystallized, and characterized by NMR. The protein has a secondary structure typical of other chemokines and forms a monomer in solution. These results indicate that total chemical synthesis can be used to accelerate the determination of three-dimensional structures of new proteins identified in genome programs.

Amino Acid Sequence↗

Solution structure of murine macrophage inflammatory protein-2.

The solution structure of murine macrophage inflammatory protein-2 (MIP-2), a heparin-binding chemokine that is secreted in response to inflammatory stimuli, has been determined using two-dimensional homonuclear and heteronuclear NMR spectroscopy. Structure calculations were carried out by means of torsion-angle molecular dynamics using the program X-PLOR. The structure is based on a total of 2390 experimental restraints, comprising 2246 NOE-derived distance restraints, 44 distance restraints for 22 hydrogen bonds, and 100 torsion angle restraints. The structure is well-defined, with the backbone (N, Calpha, C) and heavy atom atomic rms distribution about the mean coordinates for residues 9-69 of the dimer being 0.57 +/- 0.16 A and 0.96 +/- 0.12 A, respectively. The N- and C-terminal residues (1-8 and 70-73, respectively) are disordered. The overall structure of the MIP-2 dimer is similar to that reported previously for the NMR structures of MGSA and IL-8 and consists of a six-stranded antiparallel beta-sheet (residue 25-29, 39-44, and 48-52) packed against two C-terminal antiparallel alpha-helices. A best fit superposition of the NMR structure of MIP-2 on the structures of MGSA, NAP-2, and the NMR and X-ray structures of IL-8 are 1.11, 1.02, 1.27, and 1.19 A, respectively, for the monomers, and 1.28, 1.10, 1.55, and 1.36 A, respectively, for the dimers (IL-8 residues 7-14 and 16-67, NAP-2 residues 25-84). At the tertiary level, the main differences between the MIP-2 solution structure and the IL-8, MGSA, and NAP-2 structures involve the N-terminal loop between residues 9-23 and the loops formed by residues 30-38 and residues 53-58. At the quaternary level, the difference between MIP-2 and IL-8, MGSA, or NAP-2 results from differing interhelical angles and separations.

Amino Acid Sequence↗

Solution structure of a highly stable DNA duplex conjugated to a minor groove binder.

The tripeptide 1,2-dihydro-(3 H )-pyrrolo[3,2- e ]indole-7-carboxylate (CDPI3) binds to the minor groove of DNA with high affinity. When this minor groove binder is conjugated to the 5'-end of short oligonucleotides the conjugates form unusually stable hybrids with complementary DNA and thus may have useful diagnostic and/or therapeutic applications. In order to gain an understanding of the structural interactions between the CDPI3minor groove binding moiety and the DNA, we have determined and compared the solution structure of a duplex consisting of oligodeoxyribonucleotide 5'-TGATTATCTG-3' conjugated at the 5'-end to CDPI3 and its complementary strand to an unmodified control duplex of the same sequence using nuclear magnetic resonance techniques. Thermal denaturation studies indicated that the hybrid of this conjugate with its complementary strand had a melting temperature that was 30 degrees C higher compared with the unmodified control duplex. Following restrained molecular dynamics and relaxation matrix refinement, the solution structure of the CDPI3-conjugated DNA duplex demonstrated that the overall shape of the duplex was that of a straight B-type helix and that the CDPI3moiety was bound snugly in the minor groove, where it was stabilized by extensive van der Waal's interactions.

DNA↗

Local radiant heating increases subcutaneous oxygen tension.

BACKGROUND: We evaluated a novel bandage that incorporates a thermostatically controlled radiant heater. We first determined optimal bandage temperature, based on increases in subcutaneous oxygen tension, a measure correlating well with resistance to infection and wound strength. We then tested the hypothesis that prolonged radiant heating would increase collagen deposition in experimental thigh wounds. METHODS: The experimental bandages were positioned on the anterior thigh of 8 volunteers, and heated for 2 hours at 38 degrees C, 42 degrees C, or 46 degrees C, in a random order. Subcutaneous oxygen tension under the bandage was recorded from an electrode positioned within a subcutaneous tonometer. We studied 10 volunteers in the second protocol. For 1 week, the experimental bandage was continuously applied to one thigh, and heated to 38 degrees C using a 2-hour on/off cycle. On the alternate week, a standard gauze bandage was applied to the contralateral thigh. Treatment order was randomly assigned. Wound collagen deposition under each bandage was evaluated with subcutaneous polytetrafluoroethylene tubes, which were removed and assayed for hydroxyproline on the eighth day. Data are presented as means +/- SDs. RESULTS: Skin temperature during heating ranged from 36 degrees C to 37.5 degrees C. Oxygen tension increased approximately 50% during heating, but the increase was comparable at the three tested temperatures. Even after heating was discontinued, subcutaneous oxygen tension remained elevated for the remaining 3 study hours. Collagen deposition after 1 week of active heating was 3.4 +/- 1.0 microg/ cm. After 1 week of control treatment, collagen deposition was 3.2 +/- 1.1 microg/cm (P = not significant). CONCLUSIONS: Our data suggest that radiant heating at 38 degrees C significantly increases subcutaneous oxygen tension, and presumably resistance to infection. However, prolonged heating at this temperature does not increase wound collagen deposition.

Adult↗

Epidemiology and clinical impact of Pseudomonas aeruginosa infection in cystic fibrosis using AP-PCR fingerprinting.

Arbitrarily primed PCR (AP-PCR) was utilized to genetically fingerprint 252 Pseudomonas aeruginosa strains isolated from the sputa of 50 cystic fibrosis (CF) patients attending the Cork CF clinic over a period of 3 years. Ten distinct P. aeruginosa strains were identified and the distribution, temporal trends and clinical impact of colonization with these individual P. aeruginosa clones was studied. A number of random isolates from each AP-PCR group were analysed using pulsed field gel electrophoresis (PFGE) in order to confirm the discriminatory power of the AP-PCR technique. The majority of patients were colonized with a single strain over the time period of the study, but it was also possible to harbour two or more strains transiently or simultaneously. Four main strains were relatively evenly distributed throughout the CF population, and it was noted that patients from the same family or attending the same school tended to harbour the same P. aeruginosa clone. Disease severity was significantly associated with the age of the patient (P < 0.001), clearly indicating an increase in severity with increase in age. The general clinical status of the CF patients was not significantly associated with the P. aeruginosa variant isolated from their sputa. Lung status was defined by FEV1 measurement and chest X-ray score (CXR). The non parametric Kruskal-Wallis significance test of FEV1, CXR and age by colonizing P. aeruginosa clone indicated that FEV1 (P = 0.017), but not CXR (P = 0.19) or age (P = 0.842), differed significantly across the clones of P. aeruginosa isolated. Patients harbouring P. aeruginosa strains B, F or G clearly had lower FEV1 scores while those harbouring clones A, C, D or H generally had higher FEV1 scores. Thus, the sub-species variant of P. aeruginosa colonizing CF patients may be associated with the severity of progressive lung disease.

Adult↗

High-dose chemotherapy with BUCY or BEAC and unpurged peripheral blood stem cell infusion in patients with low-grade non-Hodgkin's lymphoma.

Forty-nine patients with low-grade non-Hodgkin's lymphoma (NHL) received high-dose chemotherapy (HDC) with busulfan and cyclophosphamide (BUCY) or carmustine, etoposide, cytarabine and CY (BEAC) followed by unpurged autologous peripheral blood stem (PBSC) infusion. All patients had failed initial chemotherapy or progressed after an initial remission. Peripheral blood stem cells were mobilized with CY alone (n = 1), CY, etoposide (n = 19), or CY, etoposide and cisplatin (n = 29) followed by granulocyte colony-stimulating factor. Twenty-two patients received BU, 16 mg/kg, and CY, 120 mg/kg. Twenty-seven patients received carmustine 300 mg/m2, etoposide 600 mg/m2, cytarabine 600 mg/m2, and CY 140 mg/kg. Four patients (8%) died of non-relapse causes, two (9%) in the BUCY group and two (7%) in the BEAC group. Twenty-seven patients (55%) relapsed or progressed at a median of 9.4 months (2-38) from PBSC infusion. Ten patients who relapsed are alive a median of 31 months (range, 6-47) after relapse. The probabilities of relapse at 3.6 years for patients receiving BUCY or BEAC were 0.57 and 0.70, respectively (P = 0.92). Twenty-seven patients (55%) are alive at a median of 3.6 years (range, 1-5). The probabilities of survival at 3.6 years for patients receiving BUCY or BEAC were 0.58 and 0.55, respectively (P = 0.72). The probabilities of EFS at 3.6 years for patients receiving BUCY or BEAC were 0.36 and 0.28, respectively (P = 0.82). It was concluded that BUCY is an active regimen for the treatment of patients with low-grade NHL.

Adult↗

High-dose chemotherapy in patients with breast cancer: evaluation of infusing peripheral blood stem cells containing occult tumor cells.

The purpose of this study was to evaluate the frequency of detecting occult tumor cells in peripheral blood stem cell (PBSC) harvests and to determine the impact of infusing such cells on relapses after high-dose chemotherapy (HDC). Peripheral blood stem cell harvests from 223 patients with breast cancer were examined by an immunocytochemistry (ICC) method for detection of occult tumor cells, and infused after HDC without consideration of test results. Two hundred and four patients, 114 with stage II-III and 90 with stage IV disease who received only PBSC, that were tested by ICC were evaluated for time to relapse. Five hundred and eighty-one of 619 PBSC harvests (94%) from 223 patients were tested. Fifty-three of 581 harvests (9%), 8% from stage II-III and 10% from stage IV patients, were positive by ICC (P = 0.68). Forty-one of 223 patients (18%), 17/122 (14%) with stage II-III and 24/101 (24%) with stage IV disease, had positive harvests (P = 0.06). Eleven percent of patients who had 1-2 harvests tested were positive as compared to 32% of patients who had > or =3 PBSC harvests tested (P < 0.001). Nineteen patients who were infused with a mixture of ICC negative and untested PBSC harvests were excluded from analyses of relapse. The probabilities of relapse at 18 months for the 97 patients with stage II-III disease infused with ICC-negative and the 17 with ICC-positive PBSC were 0.19 and 0.13, respectively (P = 0.48). The probabilities of relapse at 18 months for patients achieving a CR or a CR in non-bone sites and improvement in bone lesions were 0.55 for the ICC-negative group (n = 30) and 0.45 for the ICC-positive group (n = 11) (P = 0.60). It was concluded that occult tumor cells were detected by ICC in PBSC harvests from a relatively small fraction of women with breast cancer, but were not associated with a significant increase in the probability of early relapse or progression when infused after HDC.

Adult↗

Visual assessment of the accuracy of retrospective registration of MR and CT images of the brain.

In a previous study we demonstrated that automatic retrospective registration algorithms can frequently register magnetic resonance (MR) and computed tomography (CT) images of the brain with an accuracy of better than 2 mm, but in that same study we found that such algorithms sometimes fail, leading to errors of 6 mm or more. Before these algorithms can be used routinely in the clinic, methods must be provided for distinguishing between registration solutions that are clinically satisfactory and those that are not. One approach is to rely on a human observer to inspect the registration results and reject images that have been registered with insufficient accuracy. In this paper, we present a methodology for evaluating the efficacy of the visual assessment of registration accuracy. Since the clinical requirements for level of registration accuracy are likely to be application dependent, we have evaluated the accuracy of the observer's estimate relative to six thresholds: 1-6 mm. The performance of the observers was evaluated relative to the registration solution obtained using external fiducial markers that are screwed into the patient's skull and that are visible in both MR and CT images. This fiducial marker system provides the gold standard for our study. Its accuracy is shown to be approximately 0.5 mm. Two experienced, blinded observers viewed five pairs of clinical MR and CT brain images, each of which had each been misregistered with respect to the gold standard solution. Fourteen misregistrations were assessed for each image pair with misregistration errors distributed between 0 and 10 mm with approximate uniformity. For each misregistered image pair each observer estimated the registration error (in millimeters) at each of five locations distributed around the head using each of three assessment methods. These estimated errors were compared with the errors as measured by the gold standard to determine agreement relative to each of the six thresholds, where agreement means that the two errors lie on the same side of the threshold. The effect of error in the gold standard itself is taken into account in the analysis of the assessment methods. The results were analyzed by means of the Kappa statistic, the agreement rate, and the area of receiver-operating-characteristic (ROC) curves. No assessment performed well at 1 mm, but all methods performed well at 2 mm and higher. For these five thresholds, two methods agreed with the standard at least 80% of the time and exhibited mean ROC areas greater than 0.84. One of these same methods exhibited Kappa statistics that indicated good agreement relative to chance (Kappa > 0.6) between the pooled observers and the standard for these same five thresholds. Further analysis demonstrates that the results depend strongly on the choice of the distribution of misregistration errors presented to the observers.

Algorithms↗

Predicting severe angiographic coronary artery disease using computerization of clinical and exercise test data.

Currently the standard exercise test is shifting from being a tool for the cardiologist to utilization by the nonspecialist. This change could be facilitated by computerization similar to the interpretation programs available for the resting ECG. Therefore, we sought to determine if computerization of both exercise ECG measurements and prediction equations can substitute for visual analysis performed by cardiologists to predict which patients have severe angiographic coronary artery disease. We performed a retrospective analysis of consecutive patients referred for evaluation of possible or known coronary artery disease who underwent both exercise testing with digital recording of their exercise ECGs and coronary angiography at two university-affiliated Veteran's Affairs medical centers and a Hungarian hospital. There were 2,385 consecutive male patients with complete data who had exercise tests between 1987 and 1997. Measurements included clinical and exercise test data, and visual interpretation of the ECG paper tracings and > 100 computed measurements from the digitized ECG recordings and compilation of angiographic data from clinical reports. The computer measurements had similar diagnostic power compared with visual interpretation. Computerized ECG measurements from maximal exercise or recovery were equivalent or superior to all other measurements. Prediction equations applied by computer were only able to correctly classify two or three more patients out of 100 tested than ECG measurements alone. beta-Blockers had no effect on test characteristics while ST depression on the resting ECG decreased specificity. By setting probability limits using the scores from the equations, the population was divided into high-, intermediate-, and low-probability groups. A strategy using further testing in the intermediate group resulted in 86% sensitivity and 85% specificity for identifying patients with severe coronary disease. We conclude that computerized exercise ST measurements are comparable to visual ST measurements by a cardiologist and computerized scores only minimally improved the discriminatory power of the test. However, using these scores in a stratification algorithm allows the nonspecialist physician to improve the discriminatory characteristics of the standard exercise test even when resting ST depression is present. Computerization permitted accurate identification of patients with severe coronary disease who require referral.

Coronary Angiography↗

Sodium chloride-citrate beverages attenuate hypovolemia in men resting 12 h at 2800 m altitude.

BACKGROUND: The mechanism for reduction and restoration of total body water and plasma volume (PV) during initial exposure to acute altitude (ALT) is not clear but may involve involuntary dehydration; i.e., delayed voluntary fluid intake. METHOD: Ten men (24 +/- SD 3 yr, 180.8 +/- 8.1 cm height, 78.8 +/- 12.8 kg weight, 1.99 +/- 0.19 m2 surface area, and 12.2 +/- 4.0% body fat) were in a semi-reclining position for 12 h in a chamber at 2800 m (539 mmHg) ALT or at 321 m (732 mmHg; ground). They ate a controlled breakfast (450 kcal + 3 ml x kg(-1) H2O) on the ground, and lunch and dinner at ALT (or on the ground) for a total daily intake of 2850 kcal (14% PRO, 67% CHO, 16% fat, 2.6g NaCl). At hour 10 they consumed fluid-electrolyte beverages or water (12 ml x kg(-1), 948 ml x d(-1)) in 4 sessions at weekly intervals. Beverage compositions were: a) 185 mEq x L(-1) Na+, 283 mOsm x kg(-1); b) 21.6 mEq x L(-1) Na+, 365 mOsm x kg(-1); c) water at ALT; and d) water on the ground. RESULTS: After 10 h at ALT % deltaPV (Hb-Hct) decreased (p < 0.05) by: a) 9.0 +/- SE 1.5%; b) 6.2 +/- 1.7%; c) 7.4 +/- 2.2%; and d) by 9.0 +/- 2.4%, respectively. After drinking from 1000-1030 h, PV at 1200 h changed by: a) +8.3 +/- SE 2.0% (p < 0.05); b) +2.8 +/- 2.7% (NS); c) -0.9 +/- 1.5% (NS); and d) by +0.8 +/- 3.5% (NS), respectively. The similar ground-induced hypovolemia suggests a response to confinement rather than an ALT effect and involuntary dehydration does not appear to be implicated. CONCLUSION: The significant increase in PV after consuming the (a) NaCl-NaCitrate beverage indicates that drink ionic composition appears to be more important than its osmolality for restoring PV in these conditions. Practical considerations: Because this hypovolemia was probably due to the confinement rather that reduced ambient pressure, appropriate countermeasures could be consumption of isotonic beverages, elastic stockings, leg exercise, and leg elevation.

Adult↗

Proteinase inhibitors from Nicotiana alata enhance plant resistance to insect pests.

The ornamental tobacco (Nicotiana alata) produces one 6-kDa chymotrypsin inhibitor and four 6-kDa trypsin inhibitors from a single 40.3-kDa precursor protein. Three different approaches have been used to assess the potential of these proteinase inhibitors (PIs) in insect control. The first was an in-vitro approach in which all five inhibitors, the single chymotrypsin inhibitor or three of the four trypsin inhibitors were tested for their ability to inhibit gut protease activity in insects from four orders. The second approach was to incorporate the N. alata PIs in the artificial diet of the native budworm (Helicoverpa punctigera) and the black field cricket (Teleogryllus commodus). H. punctigera larvae and T. commodus nymphs had a significant (P<0.01) reduction in growth after ingestion of the PI and were more lethargic than insects on the control diet. Several of the H. punctigera larvae also failed to complete moulting at the third or fourth instar. The third approach was to express the N. alata PIs in transgenic tobacco under the control of the 35S CaMV promoter. When H. punctigera larvae were fed tobacco leaves expressing the N. alata PIs at 0.2% soluble protein, significant (P<0.01) differences in mortality and/or growth rate were observed.

Journal Article↗

Distinguishing recovery from remission in a cohort of bulimic women: how should asymptomatic periods be described?

BACKGROUND: Empirical definitions of remission and recovery from eating disorders are needed to understand outcome data and compare results across studies. METHOD: 106 treatment-seeking women with bulimia nervosa, who had abstained from binging and purging for at least 4 weeks, were followed prospectively. Relapse was defined as at least 4 consecutive weeks of either binging and purging weekly or binging two or more times per week, regardless of purging. Recovery was differentiated from remission based on the probability of relapse. The minimum number of weeks after which the risk of relapse leveled off was used as the cut-off to distinguish between the two outcomes. Kaplan-Meier methods were used to estimate the weekly probability of relapse. RESULTS: When defining remission as at least 4 weeks of being asymptomatic, a quarter of the women relapsed within 11 weeks. By 37 weeks, only 49% of the women remained asymptomatic (95% CI, 41-61). The probability of relapse was substantial for approximately a year after a woman ceased to binge and purge. CONCLUSION: Bulimia nervosa is an episodic disorder. As a conservative approach, periods of being asymptomatic that last less than 1 year should be labeled as remissions, not recoveries.

Bulimia↗

Description of 31 YAC contigs spanning the majority of Arabidopsis thaliana chromosome 5.

In order to generate a physical map of Arabidopsis thaliana chromosome 5, 142 molecular markers mapping chromosome 5 have been used in colony hybridization experiments with four Arabidopsis, ecotype Columbia, yeast artificial chromosome (YAC) libraries. This resulted in 634 YAC clones being anchored on chromosome 5. Southern blot analysis confirmed their positioning and provided data, which along with knowledge of the sizes of all the YAC clones, enabled the clones to be arranged into 31 contigs. Genetic mapping of markers located within 29 of these contigs on the Landsberg erecta/Columbia recombinant inbred lines allowed positioning of the contigs along the chromosome. A high proportion of the YAC clones were found to contain chimaeric inserts. The availability of this YAC contig map will accelerate chromosome-walking experiments, provide substrates for large-scale genomic sequencing projects and facilitate the mapping of new probes to this chromosome.

Arabidopsis↗

Collection of peripheral blood progenitor cells after the administration of cyclophosphamide, etoposide, and granulocyte-colony-stimulating factor: an analysis of 497 patients.

BACKGROUND: There is great interpatient variability in the number of peripheral blood stem cells collected, as measured by CD34+ cell content, after the administration of chemotherapy and a growth factor. The ability to predict patients who fail to yield adequate quantities of CD34+ cells would be of value. However, very few reports include large numbers of patients treated in an identical fashion. STUDY DESIGN AND METHODS: Between 1991 and 1995, 497 consecutive patients with a variety of malignant diseases received cyclophosphamide (4 g/m2), etoposide (600 mg/m2), and granulocyte-colony-stimulating factor (6 micrograms/kg/day) for mobilization and collection of a target dose > or = 2.5 x 10(8) CD34+ cells per kg. Multivariate analyses were performed to determine the factors associated with failure to achieve this target harvest. RESULTS: A median of 14.71 x 10(6) CD34+ cells per kg (range, 0.08-137.55) was harvested with a median of 2 (range, 1-11) apheresis procedures. Ninety-one percent of patients yielded > or = 2.5 x 10(5) CD34+ cells per kg. Patients with Stage II-III breast cancer, who had pretreatment platelet counts > or = 150 x 10(9) per L and patients who underwent < or = 1 prior chemotherapy regimen had improved CD34+ cell yields. However, most patients with adverse risk factors yielded > or = 2.5 x 10(6) CD34+ cells per kg. CONCLUSION: A regimen of cyclophosphamide, etoposide, and granulocyte-colony-stimulating factor led to the successful collection of adequate numbers of CD34+ cells in most patients without excessive toxicity. These observations confirm previous reports that intense prior therapy adversely affects the quantity of CD34+ cells harvested. Pretreatment and posttreatment variables did not predict with any certainty the small fraction of patients who fail to yield > or = 2.5 x 10(6) CD34+ cells per kg via multiple apheresis procedures.

Adolescent↗

Cloning and expression of two human lysophosphatidic acid acyltransferase cDNAs that enhance cytokine-induced signaling responses in cells.

Lysophosphatidic acid (LPA) and phosphatidic acid (PA) are two phospholipids involved in signal transduction and in lipid biosynthesis in cells. LPA acyltransferase (LPAAT), also known as 1-acyl sn-glycerol-3-phosphate acetyltransferase (EC 2.3.1.51), catalyzes the conversion of LPA to PA. In this study, we describe the isolation and characterization of two human cDNAs that encode proteins possessing LPAAT activities. These two proteins, designated here as LPAAT-alpha and LPAAT-beta, contain extensive sequence sequence similarities to microbial or plant LPAAT sequences. LPAAT-alpha mRNA was detected in all tissues with highest expression in skeletal muscle whereas LPAAT-beta was expressed predominantly in heart and liver tissues. Expression of these two cDNAs in an Escherichia coli strain with a mutated LPAAT gene (plsC) complements its growth defect and shifts the equilibrium of cellular lipid content from LPA to PA and other lipids. Overexpression of these two cDNAs in mammalian cells leads to increased LPAAT activity in cell-free extracts using an in vitro assay that measures the conversion of fluorescently labeled LPA to PA. This increase in LPAAT activity correlates with enhancement of transcription and synthesis of tumor necrosis factor-alpha and interleukin-6 from cells upon stimulation with interleukin-1beta, suggesting LPAAT overexpression may amplify cellular signaling responses from cytokines.

Acyltransferases↗