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Biomedical subjects

R Spencer

Publications and source records attributed to R Spencer.

At least 91 records · Page 5Linked to original sources

Resonance Raman and coherent anti-stokes Raman scattering spectra of flavin derivatives. Vibrational assignments and the zwitterionic structure of 8-methylamino-riboflavin.

Resonance Raman and coherent anti-stokes Raman scattering spectra are reported for flavins modified by deprotonation at N3 and by CH substitution for N1, N3 and N5, using laser excitation in resonance with the visible electronic transition. Vibrational shifts are used to make qualitative assignments of the observed vibrational modes. Both 8-CH3NH- and ionized 8-OH-riboflavin were found to give markedly different spectra patterns form flavin itself; this observation supports a partial zwitterionic structure for the 8-CH3NH derivatives.

Chemical Phenomena↗

Limited superficial debridement to improve corneal clarity during closed vitrectomy.

We controlled the development of epithelial edema of the cornea during closed vitreoretinal surgery even when the technique required continuous use of a contact lens by gentle debridement of only the shaggy, edematous superficial layer of wing cells, using an olive-tip irrigator. This technique may avoid the necessity of completely removing the epithelium and the attendant postoperative complications.

Contact Lenses↗

Cryopexy treatment of proliferative diabetic retinopathy. Retinal cryoablation in patients with severe vitreous hemorrhage.

Severe diabetic retinopathy with neovascular proliferation may produce severe vitreous hemorrhage that prevents laser therapy. Retinal ablation, if indicated, can be partly accomplished by cryopexy. In a small series of cases, cryotherapy to the retina was not apparently harmful and sometimes seemed beneficial. Blood absorption seemed more rapid and recurrent bleeding less frequent; however, vitreous hemorrhages in proliferative diabetic retinopathy are too variable in their natural history of absorption and recurrence to permit any definite conclusion as to the value of this method of retinal ablation. A national collaborative study with lengthy follow-ups will be necessary to determine whether chorioretinal scars produced by laser therapy and those produced by cryotherapy will afford similar protection from the forward course of proliferative diabetic retinopathy, vitreous hemorrhage and blindness. In the meantime, this report is intended to alert ophthalmologists that retinal cryoablation is a conservation alternative to "early" vitrectomy for vitreous hemorrhages from diabetic retinopathy.

Cryosurgery↗

Stimulation of intestinal calcium-binding-protein mRNA synthesis in the nucleus of vitamin D-deficient chicks by 1,25-dihydroxycholecalciferol.

Stimulation of intestinal calcium transport by the hormone 1,25-dihydroxycholecalciferol appears to involve RNA transcriptions and the synthesis of new proteins. Although one of these proteins has been identified as calcium-binding protein, no RNA molecules specifically induced by the hormone in the nucleus have been identified. Nuclear RNA from intestine of vitamin D-deficient chicks before and at various time intervals after treatment with the hormone or cholecalciferol was tested for its ability to code for calcium-binding protein in a cell-free system. Calcium-binding-protein mRNA could only just be detected in the intestinal nuclei 2h after dosing with these steroids which is the same time that it was first observed in the polyribosomes. Thus 1,25-dihydroxycholecalciferol induces the production of new calcium-binding protein by stimulating the formation and rapid release from the nucleus of new mRNA molecules for this protein. Polyribosomal translation of the mRNA continued only as long as it was being synthesized, and the maximum rate of synthesis following a pulse dose of 125ng of the hormone was the same as that observed after prolonged stimulation with cholecalciferol. The possibility that other 1,25-dihydroxycholecalciferol-dependent events may be occurring in the nucleus in the lag period between accumulation of the hormone in the intestine and the appearance of active calcium-binding-protein mRNA, and that these may ultimately control the synthesis of that mRNA, is discussed.

Animals↗

Mechanism and kinetics of iron release from ferritin by dihydroflavins and dihydroflavin analogues.

Dihydroflavins reductively release iron rapidly and quantitatively from purified horse spleen or horse heart ferritin. The NAD(P)H:flavin oxidoreductase from Beneckea harveyi is used to generate a constant concentration of dihydroflavin permitting a continuous assay for complete iron release. Sepharose-linked dihydroflavins are not competent to release ferritin iron, demonstrating that the dihydroflavin must pass through the channels of the protein shell prior to iron reduction. Several experiments fail to show any specific flavin binding site, though dihydroflavins do display saturation kinetics with very high apparent Km's. The rates of iron release by a number of dihydroflavin analogues show that the electron transfer is significantly rate determining in iron release by dihydroriboflavin, while diffusion of the dihydroflavin through the protein channel is slow in the release of iron by dihydroFMN. The rate of iron release is also dependent on the initial content of iron, having a maximum at 1200 iron atoms per ferritin.

Animals↗

Chemical and enzymatic properties of riboflavin analogues.

The chemical and enzymatic properties of 26 analogues of riboflavin are presented. These analogues include both endo- and exocyclically substituted isoalloxazines with redox potentials from -370 to -128 mV. Physical and chemical data such as the electronic absorption spectra, pKas, and redox potentials of the analogues are presented and are discussed with respect to preferred tautomeric and resonance forms. Like riboflavin, most of the analogues are shown to be catalytic oxidants of dihydro-5-deazaflavins. Analogue binding to egg white binding apoprotein has been quantitated and serves to determine the origins of binding site specificity for this protein. Nearly all of the analogues that possess D-ribityl groups are found to be processed to the FAD level by the flavokinase/FAD synthetase system of Brevibacterium ammoniagenes. Most extensively studied are the reactivities of the analogues with the NAD(P)H:flavin oxidoreductase of Beneckea harveyi. Many of the analogues are substrates in this enzymatic redox reaction, and a linear free energy-rate relation (log Vmax vs. E0' of the analogue) is seen that parallels similar relationships in the nonenzymatic oxidation of dihydro-5-deazaflavins. This suggests a common mechanism for the reactions of such diverse flavins as riboflavin, 5-deazariboflavin, and 1-deazariboflavin.

Kinetics↗

The relationship between vitamin D-stimulated calcium transport and intestinal calcium-binding protein in the chicken.

1. The rapid stimulation of intestinal Ca(2+) transport observed in vitamin D-deficient chicks after receiving 1,25-dihydroxycholecalciferol has necessitated a re-evaluation of the correlation hitherto observed between this stimulation and the induction of calcium-binding protein synthesis. By 1h after a dose of 125ng of 1,25-dihydroxycholecalciferol, Ca(2+) transport is increased. This is at least 2h before calcium-binding protein can be detected immunologically and 1h before synthesis of the protein begins on polyribosomes, and thus the hormone stimulates Ca(2+) transport before calcium-binding-protein biosynthesis is induced. 2. The maximum increase in Ca(2+) transport observed after this dose of 1,25-dihydroxycholecalciferol (attained by 8h) is similar to that observed after 1.25-25mug of cholecalciferol, but the stimulation is only short-lived, in contrast with the effect observed after the vitamin. At later times after the hormone, however, when Ca(2+) transport has declined to its basal rate, the cellular content of calcium-binding protein remains elevated. 3. Calcium-binding protein is synthesized on free rather than membrane-bound polyribosomes, which implies that it is an intracellular protein. 4. Rachitic chicks require the presence of dietary calcium for maximum stimulation of calcium-binding protein production by cholecalciferol. 5. These results suggest that calcium-binding protein is an intracellular protein, and that its synthesis may be a consequence of the raised intracellular calcium content of the intestinal epithelial cells resulting from 1,25-dihydroxycholecalciferol-stimulated Ca(2+) transport. We propose that calcium-binding-protein synthesis is necessary for maintaining the stimulated rate of Ca(2+) transport, which is initiated by other factors.

Animals↗

Thyroid gland volume estimated by use of ultrasound in addition to scintigraphy.

The method of estimating the mass of the thyroid gland from the area of the scintigraphic image has been compared with a method combining ultrasonic with scintigraphic images. The results for both methods were compared with surgical findings, and the scintiscan method alone was found to produce estimates which were on an average 79.5% of the surgical results. The corresponding estimates for the combined method were, on average, 100.4%.

Humans↗

Plasma cholinesterase variants in patients having lithium therapy.

The plasma cholinesterase variants of 190 mentally ill individuals having lithium prophylaxis have been examined. A significantly increased frequency of the E1f gene is reported. The effect of lithium nitrate and sodium nitrate on the plasma cholinesterase variants have been shown to be identical in the concentration range 25.0-50.0 mmol/l. The usual enzyme is slightly less sensitive to inhibition by either salt than the dibucaine resistant variant. The evidence suggest that the increased frequency of the E1f gene could be a genetic marker associated with some mental illness and not the result of lithium prophylaxis.

Cholinesterases↗

Ultrasonic scanning of the thyroid gland as a guide to the treatment of the clinically solitary nodule.

This study examines the diagnostic accuracy of ultrasonic scanning in the recognition of multinodular goitre in 87 patients referred for examination who were thought by the referring clinician to have a single nodule in the thyroid gland. Twenty-five were found to have multinodular glands, 23 of which were correctly identified by ultrasound. Of those who had truly solitary nodules, ultrasonic scanning enabled us to identify all 23 who had cystic lesions and 35 out of the 39 who had predominantly solid lesions. The clinical significance of these observations in the management of patients with so-called 'single nodules' is discussed.

Adolescent↗