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Biomedical subjects

J R Lloyd

Publications and source records attributed to J R Lloyd.

At least 19 recordsLinked to original sources

Reduction and removal of heptavalent technetium from solution by Escherichia coli.

Anaerobic, but not aerobic, cultures of Escherichia coli accumulated Tc(VII) and reduced it to a black insoluble precipitate. Tc was the predominant element detected when the precipitate was analyzed by proton-induced X-ray emission. Electron microscopy in combination with energy-dispersive X-ray analysis showed that the site of Tc deposition was intracellular. It is proposed that Tc precipitation was a result of enzymatically mediated reduction of Tc(VII) to an insoluble oxide. Formate was an effective electron donor for Tc(VII) reduction which could be replaced by pyruvate, glucose, or glycerol but not by acetate, lactate, succinate, or ethanol. Mutants defective in the synthesis of the transcription factor FNR, in molybdenum cofactor (molybdopterin guanine dinucleotide [MGD]) synthesis, or in formate dehydrogenase H synthesis were all defective in Tc(VII) reduction, implicating a role for the formate hydrogenlyase complex in Tc(VII) reduction. The following observations confirmed that the hydrogenase III (Hyc) component of formate hydrogenlyase in both essential and sufficient for Tc(VII) reduction: (i) dihydrogen could replace formate as an effective electron donor for Tc(VII) reduction by wild-type bacteria and mutants defective in MGD synthesis; (ii) the inability of fnr mutants to reduce Tc(VII) can be suppressed phenotypically by growth with 250 microM Ni2+ and formate; (iii) Tc(VII) reduction is defective in a hyc mutant; (iv) the ability to reduce Tc(VII) was repressed during anaerobic growth in the presence of nitrate, but this repression was counteracted by the addition of formate to the growth medium; (v) H2, but not formate, was an effective electron donor for a Sel- mutant which is unable to incorporate selenocysteine into any of the three known formate dehydrogenases of E. coli. This appears to be the first report of Hyc functioning as an H2-oxidizing hydrogenase or as a dissimilatory metal ion reductase in enteric bacteria.

Anaerobiosis

School daze.

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Biology

Radiofrequency energy for rewarming of cold extremities.

Radiofrequency (RF) coils, developed to resonate at 27.12 MHz, were evaluated for effectiveness in rewarming thermally unprotected extremities of 5 male subjects. Bare hands or bare feet were exposed to 10.0 degrees C air during a total of four exposures for each subject. Deposition of RF energy for two of the exposures (one for the hands and one for the feet) began when a predetermined surface skin temperature was achieved. Rewarming continued for 10 min while fiber-optic sensors recorded surface skin temperatures at eight locations for each hand and four locations for each foot. Results were compared to data from identical exposures but without RF rewarming. Statistically significant (P less than 0.01) warming occurred at all of the monitored locations. Our results clearly demonstrate the ability of RF energy to warm hands and feet in cold environments.

Adult

Characterization of the solution degradation products of histrelin, a gonadotropin releasing hormone (LH/RH) agonist.

The degradation products of histrelin (1, less than Glu-His-Trp-Ser-Tyr-(D-Nim-bzl-His)-Leu-Arg-Pro-NHEt) were determined in aqueous solution at pH 5.4 and 87 degrees C over an 18-day period (47% degradation). These degradation products (2-5) resulted from the cleavage of less than Glu-His and Trp-Ser peptide bonds, His-Trp diketopiperazine formation, and racemization of serine and histidine residues.

Amino Acid Sequence

All-trans retinoic acid protects against conversion of chemically induced and ultraviolet B radiation-induced skin papillomas to carcinomas.

It is becoming increasingly clear that cutaneous carcinogenesis in murine skin is a stepwise process comprising of initiation, promotion and progression. Most of the papillomas induced by an initiation-promotion protocol regress, while a few of them progress to malignant carcinomas. Progression of benign tumors into malignant cancer is critical since the latter lesions are capable of metastatic spread and eventual death. Inhibitors of the conversion process are therefore likely to be useful as cancer chemopreventive agents. All-trans retinoic acid (RA) is a known regulator of cellular proliferation and differentiation, and a known inhibitor of tumor promotion in murine skin. In this study we assessed the effect of topical application of RA on conversion of benign skin papillomas to malignant carcinomas. Papillomas were induced in SENCAR mice by topical application of 7,12-dimethylbenz[a]anthracene (DMBA) as tumor initiator followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) as tumor promoter. In SKH-1 hairless mice papillomas were induced by thrice weekly exposure to ultraviolet B (UVB) radiation. At 18 (DMBA/TPA group) and 25 (UVB group) weeks papilloma yield stabilized and no new tumors developed. Beginning at the 20th week (DMBA/TPA group) and at the 27th week (UVB group), malignant conversion was achieved by twice weekly topical application of TPA or free radical-generating compounds benzoyl peroxide (BPO), 2,2-azobis(2-amidinopropane) (ABP) and tert-butyl peroxybenzoate (BPB). Application of RA (10 micrograms/animal) 1 h prior to skin application of TPA, BPO, ABP or BPB afforded significant protection (up to 70%) only against malignant conversion mediated by free radical-generating compounds in both chemically induced and UVB-induced benign skin papillomas. On the other hand, preapplication of RA was less effective in the suppression of spontaneous malignant conversion in vehicle-treated animals. These results suggest that, in addition to their anti-tumor promoting effects, retinoids may also act as anti-carcinogens by inhibiting the process of malignant conversion induced by free radical-generating compounds.

Animals

Characterization of the solution degradation products of etintidine, an H2-receptor antagonist.

The primary solution degradation products of the antiulcer drug etintidine (1, N"-cyano-N-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]thio]ethyl]- N'-2-propynylguanidine) were determined to be the guanyl urea 2, the guanidine 3, the amine 4a, and the cyanoamine 4b. These products resulted from nitrile hydrolysis and/or intramolecular cyclization of the guanidino and propargyl groups. The amine 4a was found to be a predominant degradation product in aqueous media of pH 4-7 at 70 +/- 0.2 degrees C.

Chromatography, High Pressure Liquid

Malignant conversion of UV radiation and chemically induced mouse skin benign tumors by free-radical-generating compounds.

It is known that the free-radical-generating compound, benzoyl peroxide (BPO) enhances malignant conversion of murine skin benign papillomas into carcinomas. To further define the role of free radicals in malignant conversion, we studied the effect of various free-radical-generating compounds on the conversion of benign papillomas into carcinomas in murine skin. Papillomas were induced in Sencar mice by 7,12-dimethylbenz[a]anthracene (DMBA) initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion and in SKH-1 hairless mice by biweekly exposure to UVB radiation. After 20 and 27 weeks respectively, papilloma yield stabilized and no new tumors developed. Skin application of acetone, TPA, BPO, 2,2-azobis(2-amidino-propane) (ABP) and tert-butyl hydroperoxybenzoic acid (BPB) increased the rate of malignant conversion in both Sencar and SKH-1 mice. In general, the rate of malignant conversion was faster in UVB-induced tumors compared with DMBA-induced tumors. The relative efficacy of each agent was similar in both groups and was in the order: acetone less than TPA less than BPB less than BPO less than ABP. Our data suggest that free-radical-generating compounds may accelerate the malignant conversion of benign papillomas into carcinoma, indicating that epigenetic mechanism(s) may also be involved in this process.

9,10-Dimethyl-1,2-benzanthracene

Distinction of alpha- and beta-aspartyl and alpha- and gamma-glutamyl peptides by fast atom bombardment/tandem mass spectrometry.

A fast atom bombardment/collisional activation/linked-scan at constant B/E (tandem mass spectrometric) method is described which can distinguish between alpha- and beta-aspartyl and alpha- and gamma-glutamyl underivatized peptides. The method is based upon differences in loss of CO from aspartyl or glutamyl B-fragment ions (IB) in these isomers which are rationalized from the stability of the resultant A-fragment ions (IA). It was observed that the ratio of IB:IA which was used in this determination was dependent upon the collision cell pressure. The higher the collision cell pressure, the larger the difference between the IB:IA ratios for these linkages.

Aspartic Acid

In situ evidence for the involvement of superoxide anions in cutaneous porphyrin photosensitization.

Dihematoporphyrin ether, also known as Photofrin-II (Pf-II) is currently used in the diagnosis and management of a variety of epithelial neoplasms, in a modality known as photodynamic therapy (PDT). A major drawback of these porphyrins for PDT is their ability to evoke prolonged cutaneous photosensitization. The mechanism of tumor ablation and cutaneous photosensitization by these photosensitizers is thought to relate to the generation of one or more reactive oxygen species such as superoxide anion, singlet oxygen and hydroxyl radical. However, the role of these oxygen species has not been established unequivocally. In this study, the mechanism of Pf-II-mediated cutaneous photosensitization was examined using murine ear swelling as a marker. The mice treated with Pf-II and light demonstrated two-fold enhancement of ear swelling whereas animals treated with the SOD mimic, beta-carotene and dimethyl sulfoxide (DMSO) had considerably less ear swelling (p less than 0.01). The observed protective effect was dependent on the dose of each quencher and followed the pattern SOD mimic DMSO beta-carotene. The histopathologic alterations caused by Pf-II photosensitization were significantly alleviated by pretreatment with SOD mimic whereas beta-carotene and (DMSO) were less effective. Inhibitors of superoxide dismutase (sodium diethyldithiocarbamate) and catalase (hydroxyl amine and 3, amino 1,2,4-triazole) augmented Pf-II-mediated cutaneous photosensitization. These data provide the first in vivo evidence for the involvement of superoxide anion in cutaneous porphyrin photosensitization.

Animals

An experimental study of the flow-induced mass transfer distribution in the vicinity of prosthetic heart valves.

An experimental study of the flow-induced mass transfer distribution in the vicinity of a model disk valve and a ball valve was conducted using electrochemical techniques. Reynolds numbers ranged from 1000 to 6000, which are characteristic of physiologic conditions. Local instantaneous and time average data are presented. It was found that the flow-induced mass transfer distribution was high in regions of both low and high shear. It was also demonstrated that the fluctuations in the mass transfer to the wall of the test section around the valve are significantly affected by valve design. The regions of high mass transfer measured in this study were found to correlate very closely to regions where thrombus formations have been documented in-vivo studies.

Aorta

Experimental measurements of the flow-induced shear stress distribution in the vicinity of prosthetic heart valves.

The present study examines the local shear stress distribution occurring during flow through prosthetic valves. The electrochemical technique is a powerful tool for the study of mass transfer related phenomena and was selected for this investigation. The present investigation attempts to establish the viability of the particular application of the technique. Three test section geometries were analyzed: a straight tube, a ball-in-cage valve, and a model disk-in-cage valve, and the tests were conducted at six Reynolds numbers range from 1000 to 6000 under steady-state conditions. The model disk valve provided a base-case check on the validity of the technique since it has been employed in several previous studies and the flow through it is well documented. High shear and low shear regions are clearly evident and their locations can be pinpointed. The ball-in-cage valve was tested over the full range of Reynolds numbers. The shear profiles demonstrate a double peak in the region of the ball, a result which was unexpected. Careful study revealed that this was a result of the test section geometry. The frequency of the fluctuations in wall shear for the ball valve were found to be different than those for the disk valve indicating that the environment at the aortic wall is definitely affected by valve design. This study showed the electrochemical technique to be a valuable tool for the study of the flow through prosthetic heart valves.

Biomechanical Phenomena

The design, fabrication and evaluation of a trileaflet prosthetic heart valve.

Although prosthetic heart valves have been in existence for many years, the need for new improved designs and in-vitro evaluation techniques are apparent. This paper presents details on the design considerations, fabrication techniques and heart valve evaluation equipment. A valve performance index is discussed in light of various valve and mock circulatory test section designs. The need for national and indeed international valve evaluation techniques is made apparent.

Aortic Valve

Inflicted burns in children. Recognition and treatment.

Inflicted burns are an essential part of the battered child syndrome. One hundred forty-two nonaccidental burns (16%) were found in 872 children admitted to the burn center at the Children's Hospital of Michigan during the six-year period (1972 to 1977). Of the 1,518 cases of child abuse treated during this period, 9% were caused by intentional burns. Family instability and an inability to deal with stress in crisis were important factors in the cause of these injuries.

Battered Child Syndrome

Early laminar excision: improved control of burn wound sepsis by partial dermatome debridement.

The large mass of devitalized tissue that comprises the burn eschar is gradually becoming recognized as the principal source of complications in the burn patient. Clinical observations suggest that the topical agent silver sulfadiazine does not penetrate the eschar sufficiently to prevent bacterial infection from becoming established in the deeper levels of the wound but does penetrate to a depth of approximately 1.5 mm in bactericidal concentrations. A new technique that takes advantage of this fact, early laminar excision, has been developed at the Children's Hospital of Michigan Burn Center. The eschar is excised layer by layer with the electric dermatome under general anesthesia within the first 72 hr post burn, and the thickness of the devitalized tissue is reduced to a remnant of less than 1 mm. This is less than the depth to which silver sulfadiazine is capable of penetrating in bactericidal concentrations, and greatly enhanced control of burn wound sepsis is achieved. Early laminar excision of the eschar, combined with silver sulfadiazine dressings, aggressive resurfacing of the wound, and increased emphasis on nutrition, is an approach to management of the victims of thermal trauma that should significantly improve survival in patients with burn injuries greater than 60% body surface area.

Adolescent