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Biomedical subjects

R Spencer

Publications and source records attributed to R Spencer.

At least 19 recordsLinked to original sources
PubMed1992

Design and synthesis of novel FKBP inhibitors.

Small molecule FKBP inhibitors were prepared with inhibitory activity ranging from micromolar to nanomolar. The design of these inhibitors derives from a structural analysis of the substrates for FKBP and cyclophilin. As a consequence of this analysis two key observations were made, namely: (1) amino ketone moieties are suitable as FKBP recognition elements at the P1-P1' site and (2) the P3'-P4' site will accept a trans-olefin as a suitable mimetic of a peptide moiety. The preparation of these non-peptide inhibitors is readily accomplished by a protocol which includes the synthesis of chiral propargylic amines and their subsequent conversion into vinyl zirconium reagents.

Amino Acid Isomerases↗
PubMed1992

Conjoined twins: theoretical embryologic basis.

A theoretical basis for the embryology of conjoined twins was formulated from clinical experience with ten cases and extensive review of pertinent embryologic and clinical literature, including over 500 cases. Regarding the age old question of fusion or fission, it is concluded that there is no known embryologic process by which conjoined twins can be formed by fission but firm evidence to support fusion in all cases. Whether the fusion occurs between embryos on one embryonic disc or on two is of no consequence since they are all monovular. Intact ectoderm will not fuse to intact ectoderm, and all seven types of conjoined twins are explained by seven possible sites of union in the early embryo. One new term is proposed: parapagus, from the Greek para, meaning "side," combined with pagus, meaning "fixed"; this is the group formerly called dicephalus or diprosopos. These anterolaterally united parapagus twins must result from two nearly parallel notochords in close proximity; craniopagi and pygopagi from fusion at the cranial and caudal neuropores, respectively; cephalopagi and ischiopagi from union at the pharyngeal and cloacal membranes, respectively; thoracopagi from merging of the cardiac anlage; and omphalopagi from fusion of the umbilicus or of the edges of two embryonic discs in any area not including the above sites. Parasitic twins result from embryonic death of one twin, leaving various portions of the body vascularized by the surviving autosite. The rarity of cases (2) not easily explained by the above theories, and the nearly 6% of twins with two umbilical cords arising from the placenta would seem to support these conclusions. Should one wish to learn the methods of a conjurer, he might vainly watch the latter's customary repertoire, and, so long as everything went smoothly, might never obtain a clue to the mysterious performance, baffled by the precision of the manipulations and the complexity of the apparatus; if, however, a single error were made in any part or if a single deviation from the customary method should force the manipulator along an unaccustomed path, it would give the investigator an opportunity to obtain a part or the whole of the secret.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1992

Current concepts in retinopathy of prematurity.

Significant advances regarding understanding the etiology and treatment of retinopathy of prematurity have occurred in the 50 years since its discovery. Nevertheless, there is still a great deal to be learned. In spite of major technological advances in neonatal care, retinopathy of prematurity is a multi-factorial disease and probably cannot be completely prevented. Early intervention in the diagnosis and management of these infants has greatly improved their visual prognosis. Further studies may help pediatricians and neonatologists to understand and control associated risk factors. Ophthalmologists must continue to examine these patients early and follow them closely to control the associated treatable aspects of the disease, such as strabismus and amblyopia.

Humans↗
PubMed1992

Limiting applications of cryotherapy for severe retinopathy of prematurity.

In an effort to minimize surgical and visual morbidity of cryotherapy for retinopathy of prematurity (ROP), 18 eyes of 13 patients with 3 to 7 clock hours of stage 3 ROP with "plus" disease were treated by cryotherapy applications limited to the avascular retina adjacent to the areas of stage 3 disease. In 17 of 18 eyes, this limited use of cryotherapy was sufficient to cause regression of ROP without further treatments. After at least 3 months follow-up, ROP outcome showed a normal macular appearance in 16 eyes; two eyes developed macular dragging; no retinal detachments occurred.

Cryosurgery↗
PubMed1991

Visual outcome in infants with cicatricial retinopathy of prematurity.

Monocular grating acuities of preterm infants with retinopathy of prematurity (ROP) were measured using a forced-choice preferential-looking (FPL) procedure. Eyes were independently graded by a retinal specialist and/or pediatric ophthalmologist and assigned to anatomic outcome categories on the basis of cicatricial residua of ROP. Eyes assigned to the normal/regressed and peripheral retinal changes categories (n = 120) had normal posterior poles. The authors found that grating acuities in this group were slightly lower than those of age-matched healthy full-term infants, even when infants with amblyogenic or neurologic conditions were eliminated from the analysis. Grating acuity of eyes assigned to the macular ectopia, macular fold, partial detachment, or total detachment outcome categories (n = 60) had abnormal posterior poles, and grating acuity of these eyes was significantly related to anatomic outcome category (P less than 0.001). Follow-up data from subsets of eyes at 6 months, 12 months, or 2-5 yr after the initial acuity test suggest that early FPL acuity tests may be predictive of long-term functional outcome (r = 0.75-0.87).

Follow-Up Studies↗
PubMed1990

Vitrectomy in eyes at risk for macular hole formation.

Fifteen eyes believed to be at increased risk for macular hole formation underwent vitrectomy in an attempt to prevent macular hole formation. Full-thickness macular holes have not developed in 10 of 11 eyes with stage 1 macular holes. Four eyes were noted to have small full-thickness foveal defects (stage 2 macular holes) at the time of vitrectomy. Two of the four eyes have not progressed to macular hole formation and have 20/25 visual acuity. All patients have been followed for a minimum of 13 months (median, 18 months). The 12 eyes that have not experienced macular hole formation have had a significant (P less than 0.001) improvement in vision with seven (58%) attaining visual acuity of 20/25 or better. The postoperative foveal electroretinogram (ERG) amplitude was higher than the preoperative amplitude in five of the six eyes tested.

Aged↗
PubMed1979

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗