A simple method for the separation of inosinic acid from a mixture of ribonucleotides.
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Biomedical subjects
Publications and source records attributed to A Reiner.
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The neurotransmitter organization of striatal projection neurons appears to be less complex than once thought. Only 4 major evolutionarily conserved populations appear to be present. The neurons of two of these populations contain SP, DYN and GABA, with one of these two populations consisting of striatonigral projection neurons and the other of striatopallidal projection neurons. The two additional major populations of striatal projection neurons consist of striatopallidal and striato-nigral neurons that both contain both ENK and GABA. Although these conclusions greatly simplify the understanding of the organization of striatal projection neurons by suggesting that only a few major populations are present, these conclusions complicate understanding of neurotransmission between these neurons and their target areas by suggesting that each neuron utilizes multiple neuroactive substances to influence target neurons. Further studies will therefore be required to explore the mechanisms of neurotransmission by which striatal neurons communicate with their target areas.
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Our previous studies suggested that reduced choroidal blood flow (CBF) occurs with manipulations that yield myopic eye growth and that these reductions are primarily a consequence of the ocular enlargement. We could not entirely rule out the possibility, however, that reductions in CBF are at least to some extent antecedent and causal to the ocular enlargement. We therefore in the present study examined the effects on eye size of artificially reducing CBF by unilaterally transecting the choroidal nerves of the ciliary ganglion in four-day-old chicks. For comparison, we also transected the ciliary nerves in a second group of chicks or transected both ciliary and choroidal nerves in a third group of chicks. The effects of the nerve transections were evaluated in comparison to the effects of the orbital surgery itself (without nerve transection) in a fourth group termed the sham-operated control group. Two weeks after transection, CBF was measured using laser Doppler velocimetry, the ocular axial, nasotemporal and dorsoventral lengths were measured, and the eyes weighed. The results showed that CBF in birds with either choroidal nerve cuts or choroidal plus ciliary nerve cuts was greatly reduced in the treated eye (20-40% of nontreated eye). The treated eyes of these birds also showed gross depigmentation and histologically evident loss of the outer retina, most typically in the temporal retina. Birds with ciliary nerve cuts showed increased CBF in both eyes (131% right eye and 154% left eye compared to shams). Since ciliary nerve cuts yield fixed dilated pupils, increased CBF with ciliary nerve cuts appears consistent with the previously reported involvement of the choroidal nerves within a neural circuit subserving light-mediated upregulation of CBF. Clear effects on eye size were observed in the treated eyes in each group. The sham surgery alone yielded slight enlargement of the right eye compared to left eye, particularly in the axial dimension. In the choroidal nerve and the both nerve cut groups, nasotemporal and dorsoventral elongation were slightly diminished in the treated eyes compared to the sham-treated eyes. In contrast, enlargement of the right eye was slightly enhanced in the ciliary nerve cut group compared to the sham-treated eyes. The overall results suggest that large decreases in CBF do not enhance myopic eye growth, although large increases in CBF may.
Electrical stimulation in pigeons of the input from the medial subdivision of the nucleus of Edinger-Westphal (EWM) to the choroidal neurons of the ipsilateral ciliary ganglion, which themselves have input to the choroidal blood vessels of the ipsilateral eye, increases choroidal blood flow (ChBF). Since the EWM receives input from the contralateral suprachiasmatic nucleus (SCN), which in turn receives contralateral retinal input, the present study sought to determine if activation of the SCN by microstimulation or by retinal illumination of the contralateral eye would also yield increases in ChBF in that same eye. Using laser Doppler flowmetry (LDF) to measure ChBF, we found that electrical activation of the contralateral SCN by 100-Hz anodal pulse trains yielded increases in ChBF that were stimulus related and proportional to the stimulating current. These increases in ChBF elicited by the SCN stimulation were accompanied by increases in choroidal volume (vasodilation), but not by increases in systemic blood pressure. Furthermore, the increases could be blocked reversibly by lidocaine injection into the EWM. These results suggest that the increases in ChBF in the eye contralateral to the SCN stimulation were specifically mediated by the SCN-EWM pathway. Retinal illumination with a fiber optic light source was also found to increase ChBF in the illuminated eye, and these effects too could be blocked reversibly with lidocaine injection into the EWM or permanently by the EWM lesion. Control studies confirmed that the light-elicited increases were mediated by increases in choroidal volume (i.e. vasodilation), were not accompanied by systemic blood pressure increases, and were not artifactually generated by transocular illumination of the LDF probe. Thus, the SCN-EWM circuit may be involved in regulating ChBF in response to the level of retinal illumination and/or the visual patterns falling on the retina.
Previous biochemical and immunohistochemical studies have shown that the neurotensin-related hexapeptide LANT6 is widespread and abundant in the avian nervous system. In the present study, immunohistochemical techniques were used to show that LANT6 is present in numerous cells of the retinal ganglion cell layer in pigeons. Consistent with the possibility that these LANT6+ retinal cells might be retinal ganglion cells, it was found that (1) the distribution of LANT6+ fibers and terminals in the central retinal target areas matched the distribution of central retinal projections; (2) the LANT6+ fibers and terminals are eliminated from retinal target areas by transection of the contralateral optic nerve; and (3) LANT6+ retinal cells in the ganglion cell layer can be retrogradely labeled by injections of fluorogold in the tectum. These results suggest that LANT6 may be utilized as a neuroactive substance by the central terminals of numerous retinal ganglion cells in birds. Similar anatomical findings have been previously reported for members of several other vertebrate groups, giving rise to the possibility that LANT6 (or its homologues in nonavians) may be a phylogenetically ubiquitous neuroactive substance used by retinal ganglion cells.
We sought to determine if choroidal and outer retinal deterioration occur with age in pigeons, as they do in other species, and investigated the relationship between age-related retinal and choroidal changes. In 64 pigeons ranging in age over the pigeon lifespan (0.5-20 years), we measured some or all among the following parameters: choroidal blood flow (ChBF) by laser Doppler flowmetry, choroidal thickness and choriocapillary vessel abundance by LM histology, choriocapillary endothelial cell transport specializations by EM histology, acuity by behavioral methods, and degenerating photoreceptor abundance and total photoreceptor abundance by LM histology. Regression and Receiver Operator Curve (ROC) analyses were used to characterize the pattern of age-related changes and determine the ages at or by which significant changes occurred. For the 45 birds for which we measured choroidal parameters, choriocapillary vessel abundance showed a curvilinear decline with age and half of this decline occurred by 3.5-4.6 years. The endothelial cell transport specializations called channels also declined curvilinearly with age. Choroidal thickness was slightly increased between the ages of 3-6 years, and thereafter declined steadily so that choroidal thickness in the oldest birds was half that in the youngest. ChBF showed an abrupt decline of about 20% at 4 years and a further 20% decline thereafter. In the 53 birds for which we obtained visual acuity and/or photoreceptor data, we observed a curvilinear decline in acuity (with half the decline having occurred by 8 years) and a prominent stepwise decline of about 20% in photoreceptor abundance at 4.7 years, followed by further decline thereafter. The period of major photoreceptor loss coincided with ages during which about 10% of photoreceptors appeared to show degenerative changes (4-8 years of age). Using partial correlation analysis with the common effect of age held constant, ChBF was found to have a positive correlation with acuity. Our results show that ChBF and choroidal vascularity decline significantly with age in pigeons, as do acuity and photoreceptor abundance. Our statistical analyses suggest that prominent choroidal vascular decline preceded the visual decline, and that there is a positive relationship between choroidal and visual functions. Thus, our findings are consistent with the view that age-related decline in choroidal function might contribute to age-related vision loss in pigeons.
Choroidal blood flow (ChBF) in birds is regulated by a neural circuit whose components are the retina, the suprachiasmatic nucleus, the medial division of the Edinger-Westphal nucleus (EWM), the ciliary ganglion, and the choriod. We have previously shown that lesions of EWM appear to result in pathological alterations in the retina. To determine whether EWM lesions also lead to altered visual functions, we have examined the effects of EWM lesions on visual acuity in pigeons. Bilateral lesions of EWM were made electrolytically, and visual acuity for high-contrast, square-wave gratings was determined behaviorally about 1 year later and compared to that of a group of pigeons that had received sham lesions of EW about 1 year prior to acuity testing. Because lesions targeting EWM invariably resulted in damage to the adjoining lateral part of the Edinger-Westphal nucleus (EWL), which controls pupillary constriction and accommodation, two additional control groups were studied. In one such control group, bilateral lesions in the area pretectalis (AP), which innervates the pupillary control part of EWL and thereby controls pupillary constriction, were made and the effects on visual acuity determined about 1 year later. In the second such control group, the effects of acute accommodative and pupillary dysfunction on acuity were studied in pigeons made cycloplegic. The accuracy of all lesions was later confirmed histologically. The mean acuities of birds with AP lesions (9.1+/-1.4 cycles/deg) and sham lesions (7.1+/-1.5 cycles/deg) were not significantly different from normal, based on published normative data on pigeons. In contrast, pigeons with lesions that completely destroyed EW bilaterally showed visual acuity (2.7+/-0.1 cycles/deg) that was well below the acuity of the sham and AP-lesion control groups. The acuity of the cycloplegic pigeons (4.8+/-0.3 cycles/deg) and one pigeon with a nearly complete bilateral EWL but a unilateral EWM lesion (6.4 cycles/deg) indicated that only about half of the loss with a bilateral EW lesion could be attributed to accommodative dysfunction. Thus, bilateral destruction of EWM appears to have led to a loss in visual acuity. This conclusion suggests that disruption of adaptive neural regulation of ChBF may impair visual function. Destruction of EWM was, however, associated with damage to the somatic components of the oculomotor and trochlear nuclei. The possibility cannot be excluded that such damage also contributed to the acuity loss.
The avian ciliary ganglion (CG) controls choroidal blood flow by its choroidal neurons, and pupil constriction and accommodation by its ciliary neurons. It was previously reported that both choroidal and ciliary neurons label positively for NADPH diaphorase (NADPHd), a marker for nitric oxide synthase (NOS). To assess if this labeling is preganglionic or postganglionic and to determine if it is attributable to neuronal NOS (nNOS), we studied pigeon CG using NADPHd histochemistry and nNOS immunohistochemistry (IHC). Short-duration staining times by NADPHd histochemistry yielded intense labeling of structures that appeared to be the cap-like endings on ciliary neurons and the boutonal endings on choroidal neurons that arise from the nucleus of Edinger-Westphal (EW), and light or no postganglionic perikaryal staining. The light postganglionic staining that was observed tended to be localized to ciliary neurons. Consistent with this, NADPHd+ nerve fibers were observed in the postganglionic ciliary nerves but rarely in the postganglionic choroidal nerves. These same staining times yielded robust staining of neurons in the orbital pterygopalatine microganglia network, which are known to be nNOS+. Diffuse staining of CG perikarya was observed with longer staining durations, and this staining tended to mask the preganglionic labeling. Preganglionic NADPHd+ staining in CG with short staining times was blocked by the NOS inhibitors iodonium diphenyl (IDP) and dichlorophenol-indophenol (DPIP), but the diffuse postganglionic staining observed with the longer staining times was not completely blocked. Labeling of CG sections for substance P (SP) by IHC (which labels EW-originating preganglionic endings in CG) and subsequently for NADPHd confirmed that NADPHd was localized to preganglionic endings on CG neurons. Immunohistochemical double labeling for nNOS and SP or enkephalin further confirmed that nNOS is found in boutonal and cap-like endings in the CG. Two studies were then carried out to demonstrate that the nNOS+ preganglionic endings in CG arise from EW. First, NADPHd+ and nNOS+ neurons were observed in EW in pigeons treated with colchicine to enhance perikaryal labeling. Second, NADPHd+ and nNOS+ preganglionic endings were eliminated from CG ipsilateral to an EW lesion. These various results indicate that NOS is present in EW-arising preganglionic endings on choroidal and ciliary neurons in avian CG. NOS also appears to be found in some ciliary neurons, but its presence in choroidal neurons is currently uncertain.
73 women suffering from primary carcinoma of the fallopian tube underwent surgical excision of their tubes. The tissue was embedded in paraffin and investigated for HER-2 oncogene amplification with a quantitative polymerase chain reaction method. DNA could be extracted and successfully prepared in 65/73 samples. None of the tissue samples exhibited amplified the HER-2 oncogene. Data suggest that the HER-2 oncogene does not play a role in tumor transformation and progression in fallopian tube carcinomas. This contrasts with observations in ovarian carcinomas, with which fallopian tube carcinomas share many clinical, histological and biochemical similarities.