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Biomedical subjects

C Ford

Publications and source records attributed to C Ford.

125 records · Page 7Linked to original sources

Drosophila nuclei replicate in Xenopus eggs.

Nuclei isolated from a permanent cell line derived from Drosophila melanogaster embryos have been injected, along with a radioactive DNA precursor [3H]TTP, into Xenopus laevis eggs. In culture, less than 7% of the cells were in S phase. After a 90 min incubation, following injection into eggs, 99% of the nuclei were shown by autoradiography to have synthesized DNA. In a similar experiment, a density label BrdUTP was injected into eggs along with the nuclei. Subsequent analysis on caesium chloride gradients showed that this DNA synthesis was semi-conservative replication. Therefore we conclude that signals present in Xenopus egg cytoplasm can initiate and sustain true semi-conservative DNA replication in nuclei from an invertebrate organism.

Animals↗

Identification of some urinary metabolites of propantheline bromide in man.

The peak plasma concn. of total radioactivity occurred 6 h after a single oral dose of [carboxyl-14C; methyl-2H3] propantheline bromide was administered to a healthy man. At this time 10% of the dose was present in the total plasma volume. 2. A total of 71% dose of radioactivity was excreted in urine in 96 h after dosage, 59% dose being excreted in the first 24 h. About 5.3% of the orally administered propantheline bromide was excreted unchanged. 3. T.l.c. analysis and g.l.c.-mass spectrometry showed xanthanoic acid, hydroxyxanthanoic acid(s), and propantheline as urinary metabolites of the drug. 4. A glucuronide of xanthanoic acid, a hydroxylated propantheline and the (2-hydroxyethyl)diisopropylammonium ion were tentatively identified as urinary metabolites. Hydrolysis of propantheline and conjugation of the resulting xanthanoic acid appear to be the major routes of metabolism of this compound. 5. A mean elimination half-life of 9.2 h was obtained for the total radioactivity by pharmacokinetic analysis of plasma and urine levels of 14C.

Adult↗

Coordination of citric acid cycle activity with electron transport flux.

Feedback control between flux through the phosphorylating electron transport chain and the coordination of flux through individual steps of the citric acid cycle have been investigated under a number of different conditions of substrate availability and workloads in the isolated perfused rat heart. The transition from substrate-free perfusion to perfusion with glucose and insulin with no change of workload was associated with increases in the pool sizes of citric acid cycle intermediates except for oxaloacetate, but with an initial imbalance of flux through individual steps in the cycle and transport of anions of the malate-aspartate cycle across the mitochondrial membrane. Flux through citrate synthase initially increased while that through alpha-ketoglutarate dehydrogenase decreased. Of the components of the malate-aspartate cycle, flux through the malate-alpha-ketoglutarate exchange was increased prior to that through the glutamate-aspartate exchange and intramitochondrial aspartate aminotransferase. These changes can be accounted for on the basis of known kinetic controls of the enzyme and transport steps in response to increased pyruvate, acetyl-CoA, and NADH delivery at an approximately constant rate of ATP turnover.

Adenine Nucleotides↗

Contribution of tissue acidosis to ischemic injury in the perfused rat heart.

The isolated perfused working rat heart preparation has been used to study the effects of respiratory acidosis on myocardial metabolism and contractilly. Hearts were perfused with 5 mM glucose and 10(-2) U/ml of insulin in order to enhance metabolsim of glucose relative to that of fatty acids. After perfusion with Krebs bicarbonate medium at pH 6.6, hearts rapidly ceased performing external work and peak left ventricular pressure fell by 75% after 5 minutes. Oxygen consumption, rate of ATP generation and overall glycolytic flux also declined rapidly. After about 2 minutes of perfusion, the fall of glycolytic flux showed a partial reversal, which was largely accounted for by increased lactate production, so that glucose oxidation decreased further. The reversal of glycoltic flux could be accounted for by partial release of H+ inhibition of phospho-fructokinase by increased tissue levels of adenosine 5'-diphosphate (ADP), adenosine monophosphate (AMP) and P1 and decreased levels of adenosine triphosphate (ATP) and creatine phosphate. The increased proportion of glucose uptake converted to lactate together with an increase of the tissue lactate/pyruvate ratio could be accounted for by inhibition of the malate-aspartate cycle combined with tissue hypoxia. Lactate accumulated in the tissue as a result of a decreased permeability of the plasma membrane to lactate. Decreased oxygen delivery to the myocardium was caused by secondary constriction of the coronary vessels. In further experiments, the coronary flow was regulated by an external pump which delivered fluid at a controlled rate into the aortic cannula above the coronary arteries, and the degree of tissue hypoxia was monitored by measuring changes of pyridine nucleotide reduction state by surface fluorescence techniques. The effects of acidosis uncomplicated by possible hypoxia were compared directly with those produced by ischemic hypoxia. The effects of acidosis under these conditions were similar to those described above, and to those produced by ischemia. From these and other data it is concluded that the effects of ischemia are caused by a lowering of the intracellular pH, which decreases the rate of energy production relative to the rate of energy demand. However, it is suggested that the primary cause of the decreased peak systolic pressure with either acidosis or ischemia is not a result of a defect of energy metabolism, but is due to alteration of the calcium cycle of the heart. Possible causes of irreversible heart failure after prolonged ischemia are discussed.

Acidosis, Respiratory↗

Progress in rhesus histocompatibility typing resulting from the Second International Nonhuman Primate Histocompatibility Workshop (1973).

The Second International Nonhuman Primate Histocompatibility Workshop permitted comparison of rhesus monkey alloantisera developed in various laboratories on a single common panel of related and unrelated monkeys. Analysis of the data permits the conclusion that at least nine specificities are recognized by more than one laboratory, including six at the first locus and three at the second locus.

Animals↗

The effects of nutritional supplements on the symptoms of fibromyalgia and chronic fatigue syndrome.

This article reports the results of a within-subject design. Fifty subjects with a physician diagnosis of fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) were interviewed using a structured interview from. Each subject was interviewed initially, and again nine months later (follow-up). Subjects had, on their own, consumed nutritional supplements including freeze-dried aloe vera gel extract; a combination of freeze-dried aloe vera gel extract and additional plant-derived saccharides; freeze-dried fruits and vegetables in combination with the saccharides; and a formulation of dioscorea complex containing the saccharides and a vitamin/mineral complex. With medical treatments, approximately 25 percent of FM patients improve, but the beneficial effects of medical treatment rarely persist more than a few months. All subjects in this study had received some form of medical treatment prior to taking the nutritional supplements, but none with enduring success. Nutritional supplements resulted in a remarkable reduction in initial symptom severity, with continued improvement in the period between initial assessment and the follow-up. Further research is needed to verify these results, specifically crossover designs in well-defined populations.

Adult↗

Improved adsorption to starch of a beta-galactosidase fusion protein containing the starch-binding domain from Aspergillus glucoamylase.

We have previously shown (Chen et al., 1991) that a beta-galactosidase (beta-gal) fusion protein (BSB133) containing 133 amino acids (aa) from the C-terminus of Aspergillus glucoamylase (GA) adsorbs strongly to starch compared to beta-gal, due to the presence of the GA starch-binding domain. We have now made deletions at the N-terminus of this 133-aa region to test the minimal size required for starch binding of beta-gal fusion proteins. Three fusion proteins (BSB119, BSB103, and BSB80) were genetically engineered, containing 119, 103, and 80 C-terminal aa from GA, respectively. The fusion proteins were expressed in Escherichia coli and purified. Purified BSB119 adsorbed to native starch at least 2-fold more strongly than did BSB133 or fusion proteins with shorter tails. Adsorption isotherms generated over a wide range of initial concentrations indicated a 10-fold difference in the loading capacity of starch for BSB119 (36.5 mg of protein/g of starch) compared to beta-gal (3.7 mg of protein/g of starch). Adsorption constants calculated from the initial slopes of the isotherms indicated a nearly 30-fold difference in affinity to starch for BSB119 (Kad = 63 mL/g of starch) compared to beta-gal (Kad = 2.3 mL/g of starch). BSB119 in the presence of crude enzyme extracts also bound to starch with a high affinity compared to a beta-gal control. Potential applications of the starch-binding tail include enzyme immobilization to starch or recovery and purification of target proteins from crude extracts.

Adsorption↗

Nasogastric tube feedings in children with high-risk cancer: a pilot study.

PURPOSE: To avoid the cost and complications of total parenteral nutrition (TPN), this study was initiated to determine the feasibility of administrating nasogastric tube feedings in children receiving intensive chemotherapy (CTX) or bone marrow transplantation (BMT). PATIENTS AND METHODS: Seventeen children (aged 2 to 19 years) were entered into the study. Continuous nasogastric feedings of a glutamine-supplemented elemental diet were administered during CTX and at the time of rehospitalization for fever, neutropenia, and mucositis. RESULTS: Fourteen children were treated with CTX and 3 with BMT. Enteral tube feedings were administered for 216 days; each patient received a mean of 12.7 days. The tubes were generally well tolerated, and there were no instances of sinusitis or epistaxis. Six children received TPN in addition to enteral feedings. The hospital charges for the enteral feedings were $25,348, compared to $112,299 for the same number of days of TPN. CONCLUSIONS: Nasogastric tube insertion and enteral tube feedings in children receiving intensive CTX or BMT can be accomplished with minimal complications and significant cost savings when compared to TPN.

Adolescent↗

Clinical observations of adult intercountry adoptees and their adoptive parents.

This article presented data from interviews with 29 adult foreign-born adoptees and 23 adoptive parents, highlighting M.S.W. students' impressions of the interviewees' responses. The students' main observations stressed individualizing adoptees and their families, cautioning against falling into the all-too-easy trap of self-fulfilling labeled behavior. A second theme was the importance of each social worker's own sensitivity and attitudes toward this type of racial mixing, and emphasized professional and personal self-awareness.

Adoption↗