Biomedical subjects
Publications and source records attributed to R E Moore.
Despite Federal laws restricting inter-hospital transfers, some hospitals continue to transfer patients for purely financial reasons. To combat the financial strain of receiving inappropriate transfers, some large hospitals have established a centralized office to coordinate transfers. A well-run transfer center can aid in the overall treatment of appropriately transferred patients as well as reduce hospital costs.
To better understand the processing of the Alzheimer disease amyloid precursor protein, we have cloned and sequenced that region of the human genome coding for the amyloid peptide. Two exons separated by a 6.2kb intron define this region. Characterization of the A4 peptide amino acid sequence shows similarity to the structure of soybean trypsin inhibitor (Kunitz). Our observation describes a different region of PreA4 than the previously characterized domain of larger amyloid precursor molecules PreA4 751 and 770(2). Moreover, the exon organization, Kunitz domain duplication and transmembrane location of A4 suggest that PreA4 is similar to growth factor precursors and thus may be processed similarly.
Using radioimmunoassay we have measured the serum concentrations of the C-terminal propeptide of type I procollagen (pColl-I-C) in 12 Tanner I-II subjects (aged 9-16 years) with severe Crohn's disease (8 patients) or ulcerative colitis (4 patients) and markedly decreased growth velocity who were subjected to surgery and 50 similarly aged children with either ulcerative colitis (20 patients) or Crohn's disease (30 patients) and normal growth. Prior to operation, the mean growth velocity and pColl-I-C concentration in the former group of 12 children were 0.03 +/- 0.02 cm/month (normal greater than or equal to 0.5 cm/month) and 14.1 +/- 1.9 micrograms/dl, respectively. This pColl-I-C concentration is comparable with that previously reported for adults (5-17 micrograms/dl) and significantly lower than found in the 50 normally growing children with inflammatory bowel disease (IBD) (46.9 +/- 2.0 micrograms/dl) (p less than 0.001). All 12 children subjected to surgery had a marked increase in growth velocity and pColl-I-C concentration to 0.73 +/- 0.08 cm/month and 59.1 +/- 5.6 micrograms/dl, respectively (p less than 0.001 compared with preoperative values). Changes in pColl-I-C concentrations antedated measurable changes in linear growth. These data suggest that pColl-I-C concentrations can reflect growth velocity in children with IBD subjected to surgery and may provide a rapidly available measure of current "growth activity."
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1. Preputial gland function in male Microtus montanus is androgen-dependent, both in terms of preputial weights and in the production of a series of lipids which are present in M. montanus and absent from Microtus pennsylvanicus. 2. Production of these species-typical lipids is decreased but not eliminated in castrates, as well as in adrenalectomized castrates treated with corticosterone. Therefore, in the total absence of androgens, a low level of these lipids is still produced. 3. 5 alpha-dihydrotestosterone and 17 beta-estradiol enanthate have limited effects on maintenance of preputial weight, suggesting that testosterone itself is the active steroid in the preputial gland of this species.
We determined the serum concentration of the C-terminal propeptide of type I procollagen (pColl-I-C) in 60 children and adolescents (ages 4 to 17 years) with inflammatory bowel disease (24 ulcerative colitis, 36 Crohn disease) and in seven children (ages 2 to 15 years) with nongastrointestinal disease (asthma) during varying regimens of corticosteroid therapy. Patients with inflammatory bowel disease were grouped according to disease severity (mild, and moderate to severe). Significantly lower pColl-I-C concentrations and growth velocities were found in each severity group among those subjects receiving daily corticosteroid therapy compared with those receiving alternate-day or no corticosteroid therapy (P less than 0.01). When daily corticosteroid therapy was initiated and then maintained for 7 to 14 days in 11 patients with exacerbation of inflammatory bowel disease clinical improvement resulted, but mean procollagen concentrations decreased significantly (P less than 0.001). In seven children with asthma receiving methylprednisolone intravenously, significant decreases in pColl-I-C concentrations were noted within 24 to 48 hours of therapy (P less than 0.001). These data indicate that serum procollagen values decrease during both short- and long-term daily administration of corticosteroid therapy. Longitudinal assessment of procollagen concentrations may provide rapid assessment of the effects of different corticosteroid regimens on growth.
A methodology for determining acceptable levels for decontamination of soil containing radionuclides at waste sites is described. This methodology calculates the annual radiation dose that an individual receives while living on property that has been decommissioned and decontaminated. Pathways of exposure include direct radiation from ground surfaces, ingestion of contaminated food, inhalation of resuspended radionuclides and drinking contaminated water. Results calculated using this methodology were compared with U.S. Department of Energy (DOE) guidelines for a southeastern U.S. site. There is good agreement between the two methods provided similar assumptions are used.
A clonal isolate, termed L575, of the filamentous brackish-water cyanobacterium Nodularia spumigena Mertens emend. was found to produce a potent hepatotoxic peptide (50% lethal intraperitoneal dose for the mouse, 60 micrograms/kg) with chemical and toxicological properties similar to those of the hepatotoxic heptapeptides produced by other freshwater planktonic cyanobacteria. The isolate was made from a water sample collected in Lake Ellesmere, New Zealand, in 1980. The toxin, isolated and purified by high-performance liquid chromatography (HPLC) and analyzed by HPLC amino acid analysis, contained glutamic acid, beta-methyla-spartic acid, and arginine units in equivalent amounts. The fast-atom-bombardment mass spectrum of the toxin indicated the molecular weight to be 824. Batch cultures of strain L575 showed that the toxin content varied between 1.96 and 2.99 mg/g of cells and that a positive correlation between toxin content and chlorophyll a, but not biomass, was present.
PFC emulsions have shown considerable promise for a variety of clinical indications, but their utility has been limited by instability outside the frozen state, extended tissue residence time, and complement activation. A new formulation from Adamantech, INc. based on F-MA and egg yolk phospholipid shows significant improvement in each of these areas. The emulsion can be stored in the non-frozen state, has a tissue half-life of 8-9 days, has excellent rheological properties, and does not activate complement.
Myocardial protection during surgically-induced cardiac ischemic arrest can be improved by promoting aerobic metabolism throughout the ischemic episode. Because of the problems encountered with both blood cardioplegia and oxygenated crystalloid cardioplegia, we assessed the effects of a recently developed lecithin-based perfluoroadamantane in an isolated isovolumic buffer-perfused rat heart model of cardioplegic arrest. Forty hearts divided into 4 equal groups underwent 90 min of global ischemia at 30.C followed by 45 min of normothermic reperfusion. During arrest, hearts were infused at 30 min intervals with either standard crystalloid cardioplegic solution, lecithin-enriched cardioplegic solution or cardioplegic solution mixed with a lecithin-based perfluorocarbon emulsion (F-dimethyladamantane in one group, and F-methyladamantane in the other). All perfusates were fully oxygenated prior to use. Although fluorocarbon-treated hearts had reduced postischemic coronary flows, they yielded a significantly better recovery of systolic indexes (developed pressure and left ventricular dP/dt) than the controls. Postischemic diastolic pressures were not different among the 4 groups. We conclude that, under severe conditions of ischemia, the Adamantech fluorocarbon emulsion significantly improves cardioplegic protection. The clinical relevance of these data is supported by the fact that, unlike previously developed pluronic-based fluorocarbon emulsions, the present solution has no complement-activating properties.
Tubercidin, toyocamycin, and the corresponding 5'-alpha-D-glucopyranose derivatives of the nucleosides are frequently responsible for much of the cytotoxicity and antimycotic activity associated with extracts of cultured cyanophytes belonging to the family Scytonemataceae. The 5'-alpha-D-glucopyranoses of tubercidin and toyocamycin, for example, are the major cytotoxic and fungicidal nucleosides in Fijian Plectonema radiosum and Hawaiian Tolypothrix tenuis, respectively.
Two patients with clinically definite multiple sclerosis presented with acute hypothermia and on recovery were found to be chronically hypothermic. Thermoregulatory studies indicated a central, hypothalamic defect which is presumed to be due to a plaque of demyelination.
Blood glucose, plasma concentrations of gastric inhibitory polypeptide, insulin, glucagon, cortisol, and thyroid hormones were measured in nonobese and obese human subjects at 30 and 22 degrees C ambient temperature (Ta). Oxygen consumption (VO2), carbon dioxide output (VCO2), and temperatures in the external auditory meatus (Tc) and on the skin surface (Tsk) were also measured. After 1 h, near naked at the chosen Ta, an oral dose of sucrose (approximately 1.5 g/kg) was given and the subjects were then monitored for a further 60 or 90 min. Following sucrose ingestion, both in the nonobese and obese, there were significant (p less than 0.001) increases in the following: glucose, gastric inhibitory polypeptide, insulin, VO2, and respiratory quotient. The effect of Ta on these responses in the nonobese was that gastric inhibitory polypeptide rose more at Ta 30 than at Ta 22 (p less than 0.05) and VO2 rose more at Ta 22 than at Ta 30 (p less than 0.05). In the obese, glucose rose more at Ta 30 than at Ta 22 (p less than 0.02), VO2 rise was less than in the nonobese at Ta 22 (p less than 0.05), and the respiratory quotient was lower than in the nonobese at both Ta 30 and 22 (p less than 0.001). Gastric inhibitory polypeptide changes with respect to Ta in the obese were inconsistent. It is concluded that responses to oral sucrose are modified by environmental temperature.
The isolation and characterization of a family of maize glutathione-S-transferases (GST's) has been described previously. These enzymes are designated GSTs I, II and III based on size, substrate specificity and responsiveness to safeners. GST III has been shown to act on the herbicide alachlor as well as the commonly used substrate 1-chloro-2,4-dinitrobenzene (CDNB). Clones were isolated from a maize cDNA library in lambda gt10. Three clones contained the entire coding region for GST III. The sequences of these clones were consistent with the known amino terminal GST III protein sequence. Moreover, expression of one of these clones in E. coli resulted in a GST activity as measured with both CDNB and alachlor, proving that at least one of the clones encodes an active GST III species. With the enzyme expressed in E. coli it will become possible to study enzyme structure-function relationships ex planta. While a number of different GST proteins are present in maize tissue the GST III gene is present in single or low copy in the genome.
We have studied 15 infants with severe protein energy malnutrition (PEM) as a model of nutritional nonthyroidal illness. Changes in circulating thyroid hormones, binding proteins, and their interrelationships were assessed before and during recovery. Serum concentrations of total thyroxine and triiodothyronine and of thyroxine-binding proteins were extremely reduced, and increased progressively during 3 wk of refeeding. The T4:TBG molar ratio was initially 0.180 +/- 0.020, and increased progressively, parallel to the increases in TT4, to 0.344 +/- 0.038 after 21 days (p less than 0.025). The changes in free T4 estimates varied according to the methods used--FTI and analogue FT4 increased, dialysis FT4 fraction decreased. Serum TSH levels increased transiently during recovery. It is concluded 1) there is reduced binding of T4 and T3 to TBG in untreated PEM which takes 2-3 wk to recover; 2) there are methodological differences in evaluating free T4 levels in PEM; 3) increased TSH secretion appears to be an integral part of the recovery from PEM.
The preparation of [3H]lyngbyatoxin A by catalytic triton-proton exchange of lyngbyatoxin A and [3H]debromoaplysiatoxin by tritiation-debromination of aplysiatoxin is described. The dose-response curves for the binding of [3H]lyngbyatoxin A and [3H]debromoaplysiatoxin to a mouse epidermal particulate fraction are virtually the same as the one previously described for [3H]12-O-tetradecanoylphorbol-13-acetate ([3H]TPA). The specific binding of [3H]TPA, [3H]-lyngbyatoxin A and [3H]debromoaplysiatoxin to the mouse epidermal particulate fraction is inhibited to the same degree by unlabeled TPA, teleocidin, lyngbyatoxin A, aplysiatoxin and debromoaplysiatoxin. This study indicates that TPA, lyngbyatoxin A and debromoaplysiatoxin bind to the same high affinity receptor in mouse skin.
The acoustic reflex (AR) was recorded from 12 healthy mixed-breed dogs. Latency and amplitude were measured from ipsilateral and contralateral AR at stimulus frequencies of 1 and 2 kHz and intensities of 70 to 110 dB sound pressure level for ipsilateral AR and 70 to 120 dB hearing level for contralateral AR. Mean latencies for ipsilateral and contralateral AR were between 33.46 and 206.10 ms and between 45.26 and 180.89 ms, respectively, and amplitudes were between 0.14 and 1.79 cm3 and between 0.31 and 1.86 cm3 of air, respectively. Stimulus frequencies and intensities had significant effects (P less than 0.05) on ipsilateral and contralateral AR latencies and amplitudes. Ipsilateral and contralateral AR decays were determined by measuring compliance change during a 10-s pure-tone stimulation at frequencies of 1 and 2 kHz at an intensity of 10 dB above AR threshold. Reflex decays for 1 kHz and 2 kHz frequencies averaged 5.74% and 9.71%, respectively, for ipsilateral AR and 5.08% and 5.40%, respectively, for contralateral AR. Bilateral tympanograms and brain stem auditory-evoked responses were performed on each dog. Mean normal static compliance of the middle ear, as determined by tympanometry, was 0.15 cm3. Unilateral tenotomy of the tensor tympani muscle was done on 6 of the 12 dogs, and each of the preceding procedures were repeated within 1 week after surgical operation. Transection of the tensor tympani tendon did not alter (P greater than 0.05) the latencies or amplitudes of 1 kHz- or 2 kHz-evoked contralateral AR, the latency or amplitude of 1 kHz-evoked ipsilateral AR, or the amplitude of 2 kHz-evoked ipsilateral AR. However, the latency of 2 kHz-evoked ipsilateral AR was significantly (P less than 0.05) increased. Reflex decay increased significantly (P less than or equal to 0.001) for the contralateral reflex elicited by the 2 kHz stimulus. Neither compliance of the middle ear system nor amplitude and latency of the brain stem auditory-evoked response were affected (P greater than 0.05) by tenotomy. Since tenotomy eliminates participation of the tensor tympani in the AR, these data indicate that contraction of this muscle is not primarily responsible for the compliance changes recorded during an acoustic reflex in dogs.