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J D Reed

Publications and source records attributed to J D Reed.

At least 19 recordsLinked to original sources

VSV-G pseudotyped lentiviral vector particles produced in human cells are inactivated by human serum.

Lentiviral vectors transduce dividing and postmitotic cells and thus are being developed toward therapies for many diseases affecting diverse tissues. One essential requirement for efficacy will be that vector particles are resistant to inactivation by human serum complement. Most animal studies with lentiviral vectors have utilized VSV-G pseudotyped envelopes. Here we demonstrate that VSV-G pseudotyped HIV and FIV vectors produced in human cells are inactivated by human serum complement, suggesting that alternative envelopes may be required for therapeutic efficacy for many clinical applications of lentiviral vectors.

Animals↗

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of polygalloyl polyflavan-3-ols in grape seed extract.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was employed to characterize the polygalloyl polyflavan-3-ols (PGPF) in grape seed extracts. Masses corresponding to a series of PGPF units inclusive of nonamers were observed in the positive-ion reflectron mode. Masses of PGPF inclusive of undecamers were observed in the positive-ion linear mode, providing the first known evidence of PGPF of this size. Soluble PGPF of grape seed extracts were precipitated by complexation with Yb(3+). The PGPF were then recovered by dissolving the precipitate in water and removing the Yb(3+) by a weakly acidic cation-exchange resin (Amberlite IRP-64). Comparisons of HPLC chromatograms of the crude grape seed extract prior to precipitation with Yb(3+) and after recovery of the PGPF indicated that 96% of the phenolic compounds were precipitated and 99% of the precipitated PGPF were recovered by cation-exchange resin. These results indicate that MALDI-TOF MS is able to determine the mass distribution of complex mixtures of oligomeric PGPF and that precipitation of PGPF by Yb(3+) is useful for isolation and quantification.

Flavonoids↗

Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation.

Coronary artery disease is responsible for much mortality and morbidity around the world. Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease. Red wine and grapes contain polyphenolic compounds, including flavonoids, which can reduce platelet aggregation and have been associated with lower rates of cardiovascular disease. Citrus fruits contain different classes of polyphenolics that may not share the same properties. This study evaluated whether commercial grape, orange and grapefruit juices, taken daily, reduce ex vivo platelet activity. In a randomized cross-over design, ten healthy human subjects (ages 26-58 y, five of each gender) drank 5-7.5 mL/(kg. d) of purple grape juice, orange juice or grapefruit juice for 7-10 d each. Platelet aggregation (whole blood impedance aggregometry, Chronolog Model #590) at baseline was compared to results after consumption of each juice. Drinking purple grape juice for one week reduced the whole blood platelet aggregation response to 1 mg/L of collagen by 77% (from 17.9 +/- 2.3 to 4.0 +/- 6.8 ohms, P = 0.0002). Orange juice and grapefruit juice had no effect on platelet aggregation. The purple grape juice had approximately three times the total polyphenolic concentration of the citrus juices and was a potent platelet inhibitor in healthy subjects while the citrus juices showed no effect. The platelet inhibitory effect of the flavonoids in grape juice may decrease the risk of coronary thrombosis and myocardial infarction.

Adult↗

Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure.

Gaucher disease is caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GC). Three clinical types of Gaucher disease have been defined according to the presence (type 2 and 3) or absence (type 1) of central nervous system disease and severity of clinical manifestations. The clinical course of the disease correlates with the mutation carried by the GC gene. To produce mice with point mutations that correspond to the clinical types of Gaucher disease, we have devised a highly efficient one-step mutagenesis method-the single insertion mutagenesis procedure (SIMP)-to introduce human disease mutations into the mouse GC gene. By using SIMP, mice were generated carrying either the very severe RecNciI mutation that can cause type 2 disease or the less severe L444P mutation associated with type 3 disease. Mice homozygous for the RecNciI mutation had little GC enzyme activity and accumulated glucosylceramide in brain and liver. In contrast, the mice homozygous for the L444P mutation had higher levels of GC activity and no detectable accumulation of glucosylceramide in brain and liver. Surprisingly, both point mutation mice died within 48 hr of birth, apparently of a compromised epidermal permeability barrier caused by defective glucosylceramide metabolism in the epidermis.

Amino Acid Sequence↗

Synthetic peptide combinatorial libraries: a method for the identification of bioactive peptides against phytopathogenic fungi.

Synthetic combinatorial libraries were evaluated with an iterative process to identify a hexapeptide with broadspectrum activity against selected phytopathogenic fungi. A D-amino acid hexapeptide (FRLKFH) and pentapeptide (FRLHF) exhibited activity against Fusarium oxysporum f. sp. lycopersici, Rhizoctonia solani (anastomosis group 1), Ceratocystis fagacearum, and Pythium ultimum. The peptides showed no hemolytic or mutagenic activity. Fluorescent microscopy studies with a membrane impermeant dye indicated that fungal cytoplasmic membranes were compromised rapidly and that the nuclear membrane was also affected.

Amino Acid Sequence↗

Nitrogen metabolism of sheep and goats consuming Acacia brevispica and Sesbania sesban.

We described the effects of two East African browses, Acacia brevispica and Sesbania sesban, on nitrogen metabolism of sheep and goats. The A. brevispica had a substantial amount of proanthocyanidins (condensed tannins); S. sesban did not. The browses were fed at three levels in combination with vetch (Vicia dasycarpa) and teff straw (Eragrostis abyssinica). Fecal N, N balance, and plasma urea N (PUN) were estimated with intact animals. Ruminal ammonia (RuA) and VFA concentrations were estimated with ruminally fistulated animals. Urinary N loss, PUN, RuA, and VFA concentrations were higher for S. sesban diets than for A. brevispica diets. Fecal N was highest with diets including A. brevispica due to high levels of fecal neutral-detergent insoluble N. Nitrogen retention was highest for diets including S. sesban. Nitrogen retention was adequate for A. brevispica diets because low urinary N compensated for high fecal N. Four hypotheses describe possible effects of tannins on N metabolism: 1) escape of protein from the rumen to the lower tract; 2) increased microbial yield; 3) increase in N-containing endogenous products; and 4) protein made indigestible in tannin-protein complexes. The effect of tannins in A. brevispica on N metabolism can best be described by the formation of indigestible tannin-protein complexes, although increased production of endogenous products is also possible.

Acacia↗

Fractionation of nitrogen isotopes by mixed ruminal bacteria.

Mixed ruminal bacteria were cultured with glucose, cellulose or no carbohydrate, and ammonium bicarbonate or casein hydrolysate. Changes in amounts of bacterial ammonia and non-ammonia N were measured. Ratios of N isotopes expressed as delta 15N (delta 15N) were measured by isotope ratio mass spectrometry. When bacteria were cultured with glucose and ammonium bicarbonate, bacterial delta 15N decreased from .9 to -5.8/1000 and residual ammonia delta 15N increased from -1.4 to 12.7/1000. Fractionation of N isotope occurred during ammonia incorporation because the difference between delta 15N of ammonia and delta 15N of bacteria (delta 15N) was 18.8/1000 (P < .01). However, when casein hydrolysate was the N source, delta 15N between non-ammonia and bacteria averaged only 1.3/1000 (P > .1), indicating no fractionation of N isotopes occurred during utilization of amino acids. The amount of bacterial N was highest at 24 h of incubation when cellulose was the carbohydrate source. At that time, delta 15N between ammonia and bacteria was 8.9/1000 when ammonia was the N source, but delta 15N between non-ammonia and bacteria was 1.7/1000 when casein hydrolysate was the N source. Bacterial N decreased after 24 h when cellulose was the source of carbohydrate. Results indicate that fractionation of N isotopes occurred during ammonia incorporation, but not during incorporation of N from amino acids, deamination, and release of ammonia. Fractionation of N isotopes during incorporation of ammonia N may be used as a marker to study N metabolism by ruminal bacteria.

Amino Acids↗

Nutritional toxicology of tannins and related polyphenols in forage legumes.

Proanthocyanidins (PA) (condensed tannins) and hydrolyzable tannins (HT) are the two major classes of tannins. Proanthocyanidins are flavonoid polymers. Hydrolyzable tannins are polymers of gallic or ellagic acid esterified to a core molecule, commonly glucose or a polyphenol such as catechin. Proanthocyanidins are the most common type of tannin found in forage legumes. Problems in the analysis of tannins are that sample processing and drying decrease extraction and reactivity, suitable standards are unavailable, and quantitative analytical methods are poorly correlated with enzyme inhibition, protein precipitation, and nutritional effects. Hydrolyzable tannins are potentially toxic to ruminants. Pyrogallol, a hepatotoxin and nephrotoxin, is a product of HT degradation by ruminal microbes. Proanthocyanidins are considered to be non-toxic because they are not absorbed, but they are associated with lesions of the gut mucosa. Research on tannins in forage legumes has determined their effects on protein digestion and metabolism but more research on tannin structure in relation to digestion of specific proteins is needed. The widely accepted explanation for positive effects of PA on protein digestion and metabolism is that PA-protein complexes escape ruminal degradation and the protein is available in the lower tract. This proposed mechanism may be incorrect because PA also complex carbohydrates, endogenous proteins, and microbial products and the degradability of PA-protein complexes by ruminal microbes has not been adequately studied. Several alternative hypotheses (to escape protein) that explain the effect of PA on protein digestion and metabolism in ruminants are also consistent with experimental results on forage legumes. These include increased microbial protein synthesis, increased use of endogenous nitrogen in the rumen, and increased secretion of salivary glycoproteins. Research on manipulating the content and type of PA in forage legumes is justified because they are associated with non-bloating legumes, lower soluble non-protein nitrogen in silage, and improved efficiency of protein utilization. Research on the biosynthesis, molecular genetics, and cell biology of PA in forage legumes needs to be integrated with research on toxicology and nutrition.

Animal Feed↗

Sample preparation technique for cross-sectional transmission electron microscopy of quantum wire structures.

A novel cross-sectional sample preparation technique for quantum wire (QWR) structures is described. By coating a thin layer of Au with a designed pattern on the sample as a marker to indicate the position of the wire pattern, the location of the thinned area can be controlled precisely. An example of applying this technique to an InGaAs/GaAs QWR structure is demonstrated. This technique can also be applied to any other small dimensional structures or devices with specific regions of interest.

Gold↗

Localization of the portal vein for transjugular catheterization: percutaneous placement of a metallic marker with real-time US guidance.

Transjugular catheterization of the portal vein can be used to form a portosystemic shunt. Conventionally, the passage of a needle from the hepatic vein into the portal vein is performed with fluoroscopic monitoring only. Several methods to target the portal vein have been previously reported, including transhepatic venous catheterization, indirect portography (arterial catheterization), or skin marking based on ultrasound (US) mapping of portal landmarks. The authors used realtime US guidance to percutaneously place a small marking wire in the parenchyma next to the portal bifurcation. A 0.018-inch-diameter, 5-mm-long platinum wire is delivered through a 22-gauge echo-tipped needle placed adjacent to the right portal vein. This marking wire enabled rapid entry into the portal vein, helped avoid extrahepatic puncture, and was useful during stent deployment and positioning.

Adolescent↗

Cardiovascular MRI: current role in patient management.

The role of cardiovascular MRI in patient management is still evolving. Its capability to demonstrate anatomy without risk has made it an important supplement to ultrasound and a replacement for CT and angiography in many settings. In vivo metabolic studies of congenital and acquired diseases may be the most important future developments.

Aortic Aneurysm↗

Nutrition and sickle cell disease.

The role of protein and calorie deficiency in sickle cell disease remains poorly defined. While such features as growth retardation, impaired immune function, and delayed menarche do suggest a relationship between sickle cell disease and undernutrition, measurement of more direct nutritional parameters in these patients have yielded mixed results. Anthropometric measurements such as skinfold thickness are subnormal in many but not all reports. Serum protein levels are normal, but low values for serum lipids have been reported. Finally, one small study shows an improvement in both growth parameters and clinical course following caloric supplementation. A variety of micronutrient deficiencies have been suggested in sickle cell disease. Numerous case reports describing an exacerbation of the chronic anemia that was reversed by folic acid therapy led to routine folate supplementation. More recent studies have shown, however, that clinically significant folic acid deficiency occurs only in a small minority of sickle cell patients. Clearly, more work is necessary to define the cost/benefit ratio of routine folic acid supplementation. Pharmacological amounts of vitamin B6 and certain of its derivatives possess in vitro antisickling activities. Nevertheless, a small clinical trial failed to demonstrate any consistent hematologic effects of B6 supplementation. Several reports indicate that vitamin E levels are low in sickle erythrocytes. Since these abnormal red cells both generate excessive oxidation products and are more sensitive to oxidant stress, and because oxidants appear to play a role in ISC formation, vitamin E deficiency could well be linked to ISC formation and hemolysis. Small clinical trials, however, have again failed to produce a clear hematological response in sickle cell anemia. The role of zinc in sickle cell disease has received considerable attention. Though studies are generally small, most do support a relationship between sickle cell disease and zinc deficiency. Etiologic associations between zinc deficiency and such complications of sickle cell disease as poor ulcer healing, growth retardation, delays in sexual development, immune deficiencies, and high ISC counts have all been suggested. Most of these studies need further corroboration. Iron deficiency is now known to be a relatively common occurrence in sickle cell anemia, especially in children and pregnant women. The theoretical benefits of concomitant iron deficiency and sickle cell anemia remain to be proven in a controlled clinical trial.(ABSTRACT TRUNCATED AT 400 WORDS)

Anemia, Sickle Cell↗

Life extension.

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Aged↗

Non-reducible cyclic, and azaphenylalanyl6 analogues of somatostatin.

SSeven new analogues of somatostatin are described, along with the effects of these analogues on pentagastrin-stimulated gastric acid and pepsin secretion in conscious cats. Replacement of the cystine disulphide bridge of somatostatin with an amide bridge, with or without deletion of the N-terminal dipeptide, resulted in analogues with approximately 20% of the potency of somatostatin. Simultaneous ommision of Lys4 in the amide-bridge analogues reduced the activity of the peptides to approximately 5% of somatostatin. Substitution of Phe6 of somatostatin or an amide-bridged analogue with azaphenylalanyl resulted in peptides with no detectable activity. The results illustrate the possible importance of the basic side-chain of Lys4 for the activity of somatostatin. The lack of activity of azaphenylalanyl6 analogues of somatostatin demonstrate the extreme importance of the orientation of the side-chain of Phe6 for the activity of somatostatin, possibly for the binding to somatostatin receptors.

Amino Acid Sequence↗

Effects of thyrotrophin-releasing hormone, and methionine-enkephalin on gastric acid and pepsin secretion in the cat.

1 The effect of intravenous administration of thyrotrophin-releasing hormone (TRH) and methionine-enkephalin on gastric acid and pepsin secretions was investigated in conscious cats prepared with chronic gastric fistulae.2 TRH, 20 mug kg(-1) h(-1), did not influence unstimulated gastric acid secretion, nor gastric acid secretion stimulated by submaximal doses of pentagastrin or histamine. Pepsin secretion stimulated by pentagastrin was not influenced by TRH.3 TRH, 20 mug kg(-1) h(-1), significantly reduced the gastric acid and pepsin responses to intravenous infusion of insulin. TRH also significantly reduced the degree of hypoglycaemia seen in response to insulin. TRH, 20 mug kg(-1) h(-1), but not 5 mug kg(-1) h(-1), infused alone resulted in a significant hyperglycaemia.4 It is concluded that the reduction of insulin-stimulated gastric secretion by TRH is not dependent on the hyperglycaemic action of the peptide. The mechanism of action of TRH on insulin-stimulated secretion is discussed with respect to its site of action.5 Methionine-enkephalin or the potent analogue, D-Ala(2), Met-enkephalinamide were without effect on unstimulated gastric secretion, or secretion stimulated by pentagastrin, histamine, and insulin. The opiate receptor antagonist, naloxone, did not significantly alter the gastric acid or pepsin response to insulin.6 It is concluded that there is no evidence that opiates stimulate oxyntic glands directly, nor that the oxyntic cells may possess high affinity binding sites for opiates, nor that endogenous opiates are involved in the control of gastric secretion.

Animals↗

The effcts of sodium fluoride on gastric acid and electrolyte output in the anaesthetized cat.

1. The possibility of a Na+/H+ exchange mechanism in the presence of NaF (Bond & Hunt, 1956) has been studied in acid secreting and non-acid secreting stomachs of anaesthetized cats. 2. In non-acid secreting stomachs, although H+ loss and Na+ gain were both pH related, there was no constant relationship between the two. 3. The H+ loss in non-acid secreting stomachs could not account for the H+ loss in histamine stimulated stomachs. 4. In acid secreting stomachs the Na+ or neutral Cl- gain was only of the order of 50% of the H+ loss, and, in the presence of isosmolal NaNO3, NaF produced the same reduction in H+ but with a markedly suppressed gain in neutral chloride. 5. The NaF induced reduction in H+ output was accompanied by reductions in the total Cl- output, the K+ output and the mucosal blood flow. 6. It is concluded that the reduction in H+ output from histamine stimulated stomachs is largely a result of inhibition of secretion.

Animals↗