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Biomedical subjects

M M Murphy

Publications and source records attributed to M M Murphy.

At least 19 recordsLinked to original sources

Versatile approach to encoding combinatorial organic syntheses using chemically robust secondary amine tags.

Encoded combinatorial organic synthesis has recently emerged as a powerful tool for the discovery of biologically active compounds from complex chemical libraries. This report describes a new encoding methodology that uses chemically robust secondary amines as tags. These amines are incorporated into an N-[(dialkylcarbamoyl)methyl]glycine-coding oligomer through simple chemistry that is compatible with a wide range of polymer-supported transformations useful in combinatorial synthesis. In the decoding process acidic hydrolysis of the tagging polymer regenerates the secondary amines, which after dansylation are resolved and detected at sub-picomole levels by reversed-phase HPLC. The versatility of this strategy is demonstrated here by encoded syntheses of members of several representative heterocyclic compound classes, including beta-lactams, 4-thiazolidinones, and pyrrolidines.

Anti-Bacterial Agents

Comparison of low-pressure versus standard-pressure fixation Carpentier-Edwards bioprosthesis.

Intermediate-phase clinical results of 51 low-pressure (LP) and 234 standard-pressure (SP) fixation porcine Carpentier-Edwards (CE) valves implanted between 1977 and 1991 were compared for valve-related events. Group similarities included New York Heart Association functional class, ejection fraction, and sex. Patients with SP valves were younger (mean age, 58 versus 68 years; p = 0.0001). There were 20 in-hospital deaths (8.6%) in the SP valve group and 5 (9.8%) in the LP valve group (p = 0.79). Follow-up was 99%, with a mean of 104 months in the SP valve group versus 55 months in the SP valve group (p = 0.0001). The actuarial survival rate was 48.2% and 22.3% at 10 and 15 years, respectively, in the SP valve group and 34.1% at 10 years in the LP valve group (p = 0.42). Freedom from events at 5, 10, and 15 years in the SP valve group and at 5 years in the LP valve group was as follows: for late valve-related events, 86.3%, 51.4% and 20.2%, respectively, in the SP valve group versus 85% in the LP valve group (p = 0.44); for valve-related death, 96.4%, 93.6%, and 87.3% in the SP valve group versus 100% in the LP valve group (p = 0.20); for structural valve failure, 96%, 68%, and 35% in the SP valve group versus 100% in the LP valve group (p = 0.09); and for reoperation, 95%, 61%, and 30% in the SP valve group versus 92% in the LP valve group (p = 0.82). In conclusion, this study revealed no significant statistical difference between LP and SP valves. In the LP valve group, structural valve failure/valve-related death was not observed, perhaps indicating a more favorable result. Absolute verification of this trend awaits long-term follow-up.

Actuarial Analysis

Energy cost of wearing chemical protective clothing during progressive treadmill walking.

While chemical protective (CP) clothing is known to adversely affect physical performance, few data exist regarding the physiological response of wearing US military CP clothing during incremental, dynamic exercise. To quantify the effects of CP clothing on energy cost and to test the hypothesis that the mask contributes little to this effect, oxygen uptake (VO2) and ventilation (VE) were determined in 14 male soldiers who walked on a treadmill at 1.56 m.s-1 for 20 min each at 0, 5, and 10% grades in three clothing conditions: BDU (battledress uniform only), MASK (BDU + M-17 protective mask), and CP clothing (MASK + overgarment, gloves and boots). In BDU's, exercise intensities expressed as %VO2max were 29, 42, and 59% at the three grades, respectively. VO2 was significantly (p < 0.01) greater at all grades (range 13 to 18%) in CP clothing compared to BDU. However, no differences in VO2 were seen between BDU and MASK at any level of exercise. VE was significantly higher at the two highest grades in CP clothing compared to BDU but when expressed relative to VO2 (VE/VO2) was significantly lower at 0% and 5% grades but not at 10%. In the MASK condition, VE was significantly lower at the 10% grade and VE/VO2 was significantly lower at all grades compared to BDU. The results show that despite the mask induced hypoventilation, VO2 is unaffected at exercise intensities up to 60% of VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Social facilitation and inhibition of emotional expression and communication.

Does the presence of others facilitate or inhibit emotional expression? Female "senders" (n = 45) viewed 12 emotionally loaded slides either alone or with another sender while responses were secretly videotaped. In Study 1, 14 "receivers" guessed the type of slide viewed by dyads more accurately (eta = .366). In Study 2, 42 receivers viewed 10 senders with friends, 10 with strangers, and 10 alone. One dyad member was covered so that only 1 sender was visible. Analysis revealed significant effects of condition (alone, friend, or stranger; eta = .456), slide type (sexual, scenic, unpleasant, or unusual; eta = .325), and the Condition x Slide Type interaction (eta = .350). Strangers had overall inhibitory effects on communication accuracy, whereas friends had facilitative effects on some slides and inhibitory effects on others. Thus, both social facilitation and inhibition of expression occurred on the basis of the emotional stimulus and personal relationship involved.

Adult

Pulse voltammetry at microcylinder electrodes.

Microcylindrical electrodes are easier to construct and maintain than microdisk electrodes. In the normal-pulse mode, ranges of time parameters and electrode sizes can be found such that depletion of reactant is unimportant and the response to the analysis pulse is predicted by theory for planar conditions. Similarly, ranges of parameters are found for reverse-pulse voltammetry such that the potential-dependent response can be treated as a sequence of individual double-pulse responses. Cylindrical diffusion and convection act to replenish reactant quickly near the electrode and thus permit overall experiment times in the range of seconds. For square-wave voltammetry the shape and position of the net current response are independent of the extent of cylindrical diffusion.

Electrochemistry

A rapid method for standardization of the gated radionuclide left ventricular ejection fraction.

Radionuclide ventriculography has become the standard method for serially evaluating left ventricular ejection fraction (EF). The "gold standard" for evaluating EF is the contrast ventriculogram, which uses mathematical models to arrive at the volumes used to calculate EF. These models are subject to possible error. This paper reports the standardization of volume measurements of a digital angiographic camera system using a series of cardiac phantoms and the correlation of measurement of the EF of a series of patients whose EF was determined by digital angiography and radionuclide ventriculography.

Aged

Five cases of Thermopsis poisoning.

Various Thermopsis species are found in the foothills and plains of the Rocky Mountains. There are no reported cases of human ingestion to Thermopsis reported in the literature. We report 5 cases of ingestion of seeds or flowers where the primary symptoms were nausea, vomiting and headache of several hours duration. As few as 6 seeds produced symptoms. The common names used by parents when calling the poison center could have easily lead to misidentification and a careful history and subsequent professional identification were required to ascertain the actual plant involved.

Child

Fibroblast stimulation in schistosomiasis. VII. Egg granulomas secrete factors that stimulate collagen and fibronectin synthesis.

Tissue fibrosis in schistosomiasis is largely responsible for the important morbidity that results from infection with the trematode worms, Schistosoma. Neither the migrating larval forms (cercariae) nor the intravascular adult worms appear to incite pathological responses that are important in chronic schistosomiasis. On the other hand, eggs deposited in tissue incite chronic granulomatous inflammatory responses that are the hallmark of infection and precede the onset of adjacent tissue fibrosis. We previously reported that products of the egg granulomas can stimulate a number of relevant responses in fibroblast cultures that in vivo would be expected to promote tissue fibrosis. We report here that the granulomas secrete factors that in vitro can stimulate collagen and fibronectin synthesis in fibroblasts. We determined that activity stimulating collagen synthesis is congruent to 10 Kd (gel filtration) with a pI of congruent to 5.5 (isoelectric focusing); additional activity is also detected in some other fractions (congruent to Kd; pI approximately 7.0). In contrast, the activity stimulating fibronectin synthesis was congruent to 22 Kd with a pI of 5.5. Activity was also present in fractions of 50 Kd with pI of approximately 7.5. Fibroblasts grown in granuloma supernatant-containing medium contained greater steady-state levels of specific mRNA coding for type I procollagen and fibronectin compared with cells cultured in unsupplemented medium. These observations support the hypothesis that biologically active molecules secreted by granuloma cells are instrumental in the initiation of tissue fibrosis in schistosomiasis.

Animals

Oral intake of phosphorus can determine the serum concentration of 1,25-dihydroxyvitamin D by determining its production rate in humans.

Changes in the oral intake of phosphorus could induce the reported changes in the serum concentration of 1,25-dihydroxyvitamin D (1,25-(OH)2D) by inducing changes in its production rate (PR) or metabolic clearance rate (MCR), or both. To investigate these possibilities, we employed the constant infusion equilibrium technique to measure the PR and MCR of 1,25-(OH)2D in six healthy men in whom the oral intake of phosphorus was initially maintained at 1,500 mg/70 kg body weight per d for 9 d, then restricted to 500 mg/d (coupled with oral administration of aluminum hydroxide) for 10 d, and then supplemented to 3,000 mg/d for 10 d. With phosphorus restriction, the serum concentration of 1,25-(OH)2D increased by 80% from a mean of 38 +/- 3 to 68 +/- 6 pg/ml, P less than 0.001; the PR increased from 1.8 +/- 0.2 to 3.8 +/- 0.6 micrograms/d, P less than 0.005; the MCR did not change significantly. The fasting serum concentration of phosphorus decreased from 3.5 +/- 0.2 to 2.6 +/- 0.2 mg/dl, P less than 0.01. With phosphorus supplementation, the serum concentration of 1,25-(OH)2D decreased abruptly, reaching a nadir within 2 to 4 d; after 10 d of supplementation, the mean concentration of 27 +/- 4 pg/ml was lower by 29%, P less than 0.01, than the value measured when phosphorus intake was normal. The PR decreased to 1.3 +/- 0.2 micrograms/d, P less than 0.05; the MCR did not change significantly. The fasting serum concentration of phosphorus increased significantly, but only initially. These data demonstrate that in healthy men, reductions and increases in the oral intake of phosphorus can induce rapidly occurring, large, inverse, and persisting changes in the serum concentration of 1,25-(OH)2D. Changes in the PR of 1,25-(OH)2D account entirely for the phosphorus-induced changes in serum concentration of this hormone.

Administration, Oral

Comparative anaerobic power of men and women.

The purpose of this study was to determine the differences in anaerobic power (AnP) between men and women and the contribution of anthropometric variables in accounting for these differences. There were 18 female and 19 male subjects who performed the 30-s Wingate test where power outputs in watts are expressed as mean power (MP, the mean for 30 s) and peak power (PP, the highest 5-s interval). Thigh volume (TV), lean body mass (LBM) and body weight (BW) were used as anthropometric variables. Absolute AnP of men was 35% and 40% higher (p less than 0.001) than that of women for PP and MP, respectively. These differences decreased to 10% and 17% for PP and MP when expressed relative to kg LBM. Anthropometric variables explained less than 50% of the variation in PP and MP for men, while in women, TV accounted for 66% and 71% of the variation in PP and MP, respectively. When the data were combined, TV, BW, and LBM explained 48%, 74%, and 79% of variation in MP and 53%, 71%, and 76% in PP, respectively. These data show that gender differences in indices of AnP are similar to those reported for muscular strength and aerobic power. Additionally, a larger portion of the between gender variation compared to the within gender variation in AnP can be accounted for by anthropometric variables.

Adolescent

Maximal power outputs during the Wingate anaerobic test.

The purpose of this study was to determine the resistance loads which elicit maximal values of power output (PO) during performance of the Wingate test (WT). Nineteen male subjects (mean age, 25.1 yrs; mean VO2 max, 3.52 l/min) performed multiple WTs in a random order at resistances ranging from 3.23 to 6.76 joules/pedal rev/kg BW. Tests were carried out on a Monark cycle ergometer modified to permit instantaneous application of resistance. Revolutions were determined by a computer interfaced frequency counter. The mean resistances eliciting the highest peak power (PP) and mean power (MP) outputs were 5.65 and 5.53 joules/pedal rev/kg BW, respectively (average of 5.59 joules/pedal rev/kg BW). Both PP and MP were significantly higher (15.5% and 13.0%, respectively) using a resistance load of 5.59 compared to the Wingate setting of 4.41 joules/pedal rev/kg BW. The test-retest reliability for PP and MP ranged between 0.91 and 0.93 at both resistance loads. Body weight and thigh volume did not significantly estimate the individual resistances eliciting maximal POs. The data suggest that resistance be assigned according to the subjects BW but consideration be given to increasing the resistance from that presently used in various laboratories.

Adult

Ossified skeletal muscle angioma: report of two cases.

Ossifying skeletal muscle angiomas are relatively rare occurrences. The preoperative diagnosis is exceedingly difficult, although ossification may be reflected radiologically as a "Swiss cheese" appearance. Two patients are described whose skeletal muscle angiomas contained osseous tissue. The osseus tissue varied from microscopic foci to an abundant amount which was readily recognizable radiologically. The pathologic and radiological features are discussed and these appearances to hemangioma and lymphangioma are presented.

Adult

Synchronization of mitochondrial DNA synthesis in Chinese hamster cells (line CHO) deprived of isoleucine.

Mitochondrial DNA (mit-DNA) synthesis was compared in suspension cultures of Chinese hamster cells (line CHO) whose cell cycle events had been synchronized by isoleucine deprivation or mitotic selection. At hourly intervals during cell cycle progression, synchronized cells were exposed to tritiated thymidine ([(3)H]TdR), homogenized, and nuclei and mitochondria isolated by differential centrifugation. Mit-DNA and nuclear DNA were isolated and incorporation of radioisotope measured as counts per minute ([(3)H]TdR) per microgram DNA. Mit-DNA synthesis in cells synchronized by mitotic selection began after 4 h and continued for approximately 9 h. This time-course pattern resembled that of nuclear DNA synthesis. In contrast, mit-DNA synthesis in cells synchronized by isoleucine deprivation did not begin until 9-12 h after addition of isoleucine and virtually all [(3)H]TdR was incorporated during a 3-h interval. We have concluded from these results that mit-DNA synthesis is inhibited in CHO cells which are arrested in G(1) because of isoleucine deprivation and that addition of isoleucine stimulates synchronous synthesis of mit-DNA. We believe this method of synchronizing mit-DNA synthesis may be of value in studies of factors which regulate synthesis of mit-DNA.

Animals