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Biomedical subjects

D M Robertson

Publications and source records attributed to D M Robertson.

At least 271 records · Page 15Linked to original sources

Changes in the proteins of wool following treatment of sheep with epidermal growth factor.

Administration of epidermal growth factor (EGF) extracted from mouse submaxillary gland to Merino sheep resulted in a temporary inhibition of the activity of the wool follicles. Subsequently, either complete discontinuities appeared in the fibers resulting in shedding of the entire fleece, or incomplete, in which case the fleece was retained but bore a zone of weakness. The protein composition of the first sample of wool harvested from 1 sheep following infusion for 66 hr with 27.5 mg EGF (0-2 weeks posttreatment) was similar to pretreatment wool. This represented wool fibers which were already present in the follicles at the beginning of infusion. Thereafter, the composition of the wool changed progressively, reaching a maximum divergence from the control in the 3-4 week regrowth period followed by a return to normal by about 10 weeks. Over this period the content of high-sulfur proteins first rose from an initial 19% to a maximum of 30%, then returned to 19%, while the high-tyrosine protein content initially decreased from 12% to 5% and then slowly increased to 12%. In addition to changes in overall protein composition, two-dimensional electrophoresis revealed alterations in the proportions of some individual protein components. These changes were similar to those observed with many other wool growth inhibitors. Smaller doses of EGF (5.8 and 2.9 mg but not 1 mg) had similar effects on wool composition but these were of lower magnitude and there was a delay in reaching a maximum response. Even after 16-18 weeks the wool from these treated sheep differed slightly in composition from the pretreatment samples.

Animals↗

The effects of chronic human chorionic gonadotropin treatment on Leydig cell function.

The purpose of this study was to examine the effect of chronic daily hCG treatment on interstitial cell function in the rat, as judged by plasma testosterone levels, the testicular binding of labeled hCG, and the capacity of the testis to respond to gonadotropin stimulation by the production of testosterone in vitro. TWenty-four hours after the first injection of 100 IU hCG there was a significant decline in hCG binding to testis homogenates and an inability to respond to hCG stimulation in vitro, After 7 days of daily injections of 10 IU or 100 IU hCG, the loss of hCG binding was maintained. However, despite the marked decline in hCG binding, there was an enhanced testosterone response to hCG stimulation in vitro, and plasma testosterone levels were significantly elevated. With continued injections of hCG for 14 or 21 days, the testes remained hyperresponsive to hCG stimulation in vitro, but hCG binding returned to control levels, and plasma testosterone concentrations declined and were not statistically different from controls. The latter changes probably result from the formation of specific hCG antibodies (Kd at 4 C, 7.8 +/- 4.5 X 10(-10) M) that were detected in plasma from rats treated for 14 or mopre days with hCG. The formation and levels of the hCG antibodies in these animals were sufficient to neutralize the effects of the exogenous hCG, thereby returning plasma testosterone levels to normal and restoring the complement of hCG receptors.

Animals↗

Heterogeneity of rat pituitary gonadotropins on electrofocusing; differences between sexes and after castration.

Anterior pituitary extracts from intact and 4 week postcastration male and female rats were electrofocused in sucrose density gradients within the pH range 3.5-10. Column fractions were combined to cover this pH range in 0.5 pH units and assayed for LH by in vitro bioassay and RIA and for FSH by radioreceptor assay and RIA. The pH distribution of bioactive LH was altered after castration in both sexes, with the proportion of recovered activity in the alkaline pH range increasing (P less than 0.01) from 52-57% in the intact animal to 71-73% after castration. In addition, significantly more bioactivity was recovered in the pH range 7-9.5 with the male (37%) than with either of the female (diestrous, 30% or proestrous, 28%) groups (P less than 0.05). FSH receptor binding activity was located in the pH region 3.5-6.5. Significantly less receptor binding activity was recovered in the pH range 3.5-4.5 with the female groups (39% and 37% diestrous and proestrous, respectively) than the male group (61%; P less than 0.05, P less than 0.01). The distribution of immunoreactive LH and FSH was similar to that observed with the LH in vitro bioassay and FSH radioreceptor assay. It is concluded that the charge distribution of pituitary gonadotropins is altered according to the sex of the animal and after castration. These findings provide further evidence that the type of gonadotropin produced by the pituitary is under endocrine control.

Animals↗

Plasma concentrations and urinary excretion of mouse epidermal growth factor associated with the inhibition of food consumption and of wool growth in Merino wethers.

Twenty-four adult Merino wethers were given mouse epidermal growth factor (mEGF) subcutaneously at doses ranging from 0.02 to 0.12 mg/kg body weight or intravenously in the dose range 0.10 to 0.14 mg/kg body weight for periods ranging from 3 to 48 h. Plasma concentrations of mEGF were measured by radioimmunoassay and effects of treatment on food consumption and wool growth were observed. Plasma concentrations of the protein sustained for 15-24 h at about 20 ng mEGF/ml (or exceeding this) almost invariably caused feed rejection and casting of the fleeces. This last result clearly indicated disruption of proliferative activity among the replicating cells in wool follicles which regulate wool growth. The inhibitory effects on appetite and wool growth of smaller doses of the protein and of plasma concentrations equal to those above which were sustained for shorter periods have also been examined. Approximately 10% of the dose of mEGF appeared in the urine of three sheep 1 to 3 days after the start of s.c. infusions of 5 mg for 7 h.

Animals↗

Intracerebral arteriolar permeability to lanthanum.

Lanthanum, an electron-dense tracer, has been used extensively in the study of the structure of cell junctions. The present study was undertaken to determine whether the interendothelial junctions of normal intracerebral arterioles allow passage of lanthanum and to document the alterations occurring in these structures in acute hypertension. Perfusion of lanthanum for 12-40 minutes in control animals resulted in passage of tracer into arteriolar walls and into the extracellular compartment of the surrounding brain. The two principal mechanisms associated with tracer extravasation into the brain were diffuse passage through endothelial cytoplasm and through interendothelial spaces bypassing tight junctions. The latter finding has not been previously reported in normal cerebral arterioles and suggests that the tight junctions of these vessels are different from those of capillaries and consist of a meshwork of closely arranged maculae occludentes rather than complete circumferential occluding bands as was previously believed. Hypertensive animals showed accelerated passage of lanthanum, it being demonstrable not only in arteriolar walls but in capillary and venular walls and the surrounding neuropil after only 5 minutes of circulation. Passage of tracer through vessel walls occurred by the same routes as in control. In addition, increased numbers of pinocytotic vesicles were observed in the endothelium, confirming our previous studies that increased vesicular transport occurs in cerebral arteriolar endothelium in acute hypertension.

Animals↗

Batrachotoxin induced axonal necrosis in peripheral nerves.

Batrachotoxin (BTX) depolarizes electrogenic membranes and also blocks axonal transport. We demonstrate that when applied in doses sufficient to block impulse transmission and axonal transport, BTX induces axonal necorsis. It is postulated that axonal necrosis is secondary to influx of sodium ions and water.

Animals↗

Radioactive phosphorus-uptake-testing variables before and after enucleation.

Values for radioactive phosphorus uptake from 23 eyes with malignant melanomas of the choroid were compared before and after enucleation. In all but two eyes, the percentage increase in 32P uptake was higher immediately after enucleation than before enucleation. In 11 eyes, the variation was more than 100%. In one eye, the percentage increase of 32P uptake was 68% before enucleation and 137% after enucleation. The clinical importance of our findings is that pressure on the globe by the detector probe before enucleation may locally decrease choroidal blood volume thereby causing an increase in the calculated 32P uptake.

Blood Volume↗

Ocular histopathology in multiple endocrine neoplasia type 2b.

Multiple endocrine neoplasia type 2b is a syndrome, often familial, characterized by medullary carcinoma of the thyroid gland, pheochromocytoma, and many mucosal neuromas in patients who frequently have a marfanoid habitus. The ophthalmic findings are distinctive and include conjunctival and eyelid neuromas, keratoconjunctivitis sicca, and, most characteristically, greatly thickened corneal nerves. Ocular histopathologic study of a 30-year-old man demonstrated thickened nerves in the ciliary body, iris, and corneoscleral limbal regions. In these regions, the nerves were a mixture of myelinated and unmyelinated fibers. Sections through the thickened corneal nerves, 1.5 mm centrally from the corneoscleral limbus, showed only nonmyelinated nerves associated with Schwann cells. The many axons were normal in appearance but varied in diameter; some were between 0.1 and 0.2 ng and others between 1.0 and 1.4 ng. An unexpected finding was numerous ganglion cells in the ciliary body. The subconjunctival tissue showed neuromas with a minimum of fibrous structure. Sections of the lacrimal gland showed normal glandular tissue.

Adult↗

Prognosis for central vision and anatomic reattachment in rhegmatogenous retinal detachment with macula detached.

We analyzed a total of 473 eyes with rhegmatogenous retinal detachment and macular involvement for significant factors relating to anatomic success and a favorable visual outcome of 6/15 (20/50) or better. The overall success rate was 90% (427 of 473 eyes). Visual acuities of 6/15 (20/50) or better postoperatively were present in 37% (174 of 470 eyes). Important factors related to both anatomic success and favorable functional results were preoperative visual acuities of 6/15 (20/50) or better, retinal detachments that were less than total, detachments with tears located at or anterior to the equator, absence of giant retinal tears, absence of either preoperative ocular hypotony (tension less than 5 mm Hg) or ocular hypertension (intraocular pressure greater than 20 mm Hg), detachments managed by nondrainage techniques, a single operation with less than 50 cryoapplications, and noncircumferential buckling. Among the other factors related to favorable visual results were detachments lasting less than one month, a shallowly rather than highly detached macula, the absence of fixed retinal folds, a patient age of less than 60 years, and the absence of postoperative choroidal detachments sufficient to cause glaucoma. We found no statistical relationship between either anatomic success or functional result and the presence of aphakia, demarcation lines, vitreous hemorrhage, detachments of the pars plana epithelium, or predetachment glaucoma being treated.

Adolescent↗

Metastatic tumor to the retina and vitreous cavity from primary melanoma of the skin: treatment with systemic and subconjunctival chemotherapy.

The cases of two young women with metastatic tumors to the retinas and vitreous cavities from primary melanoma of the skin are discussed. Each presented with 20/20 central visual acuity in both eyes and complaints of floaters related to singularly unusual golden brown cellular aggregates infiltrating the vitreous cavities. Some cells appeared to be emanating from the region of the optic nerves whereas others appeared to originate from the superficial retina, presumably from the retinal vessels. The cellular aggregates were comprised of malignant melanoma cells as determined by histocytology of a vitrectomy specimen in one case and an aqueous aspirate in the other. The clinical appearance of cellular aggregates in the form of regular spherules should alert the clinician to the possibility of malignant rather than inflammatory cellular infiltration. The combined administration of repeated systemic and subconjunctival DTIC in case 1 and BCNU in case 2 was unsuccessful in promoting tumor regression. Histology of one eye, removed because of uncontrolled neovascular glaucoma, revealed numerous melanoma cells in the superficial retina and adjacent vitreous.

Adult↗

Experimental porphyric neuropathy: a preliminary report.

An experimental model for the study of porphyric neuropathy is presented. Injection of either tetraphenyl-porphinesulfonate (TPPS), hematoporphyrin derivative (HpD), or delta-amino-levulinic acid (ALA) into mice resulted in markedly decreased motor nerve conduction velocity (MNCV). THe MNCV returned to normal within one week following the injection of large doses of ALA, and within three weeks following the injection of close to lethal doses of HpD, but there was no recovery of nerve function within 50 days following injection of substantially smaller doses of TPPS. Ultrastructural examination of motor nerves at various times following TPPS injection revealed the gradual development of structural abnormalities. Ultrastructural examination of the same nerves after a single dose of either ALA or HpD failed to demonstrate any abnormalities. The present observations call for precaution as to the use of TPPS as photosensitizer in human cancer treatment.

Aminolevulinic Acid↗

Cerebrovascular permeability in mechanically induced hypertension.

Our previous studies of cerebrovascular permeability in angiotensin-induced acute hypertension demonstrated that the principal mechanism resulting in increased permeability is enhanced pinocytosis. In order to exclude the possibility that the enhanced pinocytosis was a direct effect of exogenous angiotensin, cerebrovascular permeability alterations were studied in nonpharmacologically induced acute hypertension. Rats receiving horseradish peroxidase (HRP) intravenously, were sacrificed 2 1/2 minutes after the onset of hypertension induced by placing a clip on the abdominal aorta. These animals showed the same pattern of permeability alterations as had been observed previously in animals with angiotensin-induced acute hypertension. Focal segments of penetrating arterioles in the temporal and parietal cortex showed increased permeability to HRP. Permeable vessels showed increased numbers of pinocytotic vesicles and the interendothelial junctions revealed no alterations. Enhanced pinocytosis appears to be the principal mechanism resulting in increased cerebrovascular permeability in this model as well as suggesting that the alterations of cerebrovascular permeability observed previously in angio-tensin-induced acute hypertension occur due to the hypertensive state and are not a direct drug effect of exogenous angiotensin.

Animals↗

Morphological changes in spontaneously hypertensive rats.

Our previous studies of angiotension-induced acute hypertension showed increased intracerebral arteriolar permeability associated with markedly enhanced pinocytosis. This study was performed to determine whether similar findings occurred in spontaneous non-pharmacologically induced chronic hypertension. Cerebrovascular permeability to horseradish peroxidase (HRP) was studied over an 82-week period in spontaneously hypertensive rats (SHR) derived from a strain that originated from Japan. In a few animals increased cerebrovascular permeability to HRP was observed, associated with enhanced pinocytosis. Quantitatively, the number of pinocytotic vesicles in permeable arteriolar segments was significantly increased suggesting that enhanced pinocytosis is the principal mechanism of early cerebrovascular changes in SHR. Light microscopy of renal, ocular and cerebral vessels revealed medial hyperplasia affecting renal vessels at 16 weeks and occurring later in ocular and cerebral vessels. Deposition of fibrin in renal vessels was observed from 64 weeks onwards but was not associated with renal failure.

Animals↗

Long-term follow-up of occlusion of the central retinal vein in young adults.

We did a long-term follow-up study of 42 patients aged 40 years and younger who had occlusion of the central retinal vein in order to learn its course and determine the frequency of related systemic disorders. Two groups of venous occlusion (complete and incomplete) were delineated by initial ocular findings. Final visual prognosis could not be predicted by the severity of the venous occlusion at the time of diagnosis. The presence of anomalous disk vessels closely correlated with a favorable prognosis in patients who had complete occlusion of the central retinal vein. None of the patients with incomplete central vein occlusion developed neovascular glucoma; three (14%) of the 21 patients with complete venous occlusion developed neovascular glucoma, which resulted in enucleation. Significant associated systemic maladies included cardiovascular disease and diabetes mellitus. An apparent correlation exists between occlusion of the central retinal vein and early death.

Adolescent↗