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Ethics, Medical↗
Biomedical subjects
J Stone
Publications and source records attributed to J Stone.
Ontogeny of catecholaminergic and cholinergic cell distributions in the cat's retina.
The development of catecholaminergic and cholinergic neurones in the cat's retina has been examined with antibodies against their respective rate-limiting enzymes, tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT). ChAT-immunoreactive (IR) cells were first detected at E (embryonic day) 56 with somata in the ganglion cell layer (GCL) or in the inner cytoblast layer (CBL). At P (postnatal day) 1, two faint bands of ChAT-IR fibres were evident in an inner and outer strata of the inner plexiform layer (IPL) and by P26, the bands were similar to those in the adult. TH immunoreactivity was first detected at E59 in either darkly labelled somata in the inner CBL with processes extending toward the IPL or in lightly labelled somata also located in CBL but with no processes. At P1, most TH-IR cells had prominently labelled dendrites and, by P8, most of the features of the adult cells were evident. Soma size gradients among TH-IR cells were first detected at P8, with cells in temporal retina being larger than those in nasal retina or at the area centralis. The smaller sizes of cells at the area centralis emerged after P26. The smaller sizes of ChAT-IR somata at the area centralis, by contrast, emerged between P8 and P26. The number of both TH-IR and ChAT-IR cells declined from the time they first appeared till adulthood. The decline was smaller among ChAT-IR cells (24%) than among TH-IR cells (68%). In distribution, the differential expansion of the retina appeared to be largely responsible for generating the final adult distribution of ChAT-IR cells. However, during late postnatal development (P26 to adulthood), the density of ChAT-IR cells in the periphery declined more than that of the ganglion cells, suggesting that some ChAT-IR cells may die in the periphery during this time. Prior to P26, the changes in the distribution of TH-IR cells were inconsistent with the pattern of retinal expansion. It is suggested that during this period, regional cell loss and cell addition may account for the changes in distribution of TH-IR cells. Later in development (P26 to adulthood), the changes in the density of TH-IR cells closely conformed to the differential expansion of the retina.
Aging↗
Origin of retinal astrocytes in the rat: evidence of migration from the optic nerve.
To test recent ideas on the origin of retinal astrocytes, we have studied the spread of astrocytes in the developing retina of the albino rat. Astrocytes were identified with antibodies to their intermediate filaments, glial fibrillary acidic protein (GFAP). Astrocytes were first detected at E(embryonic day) 18, forming a corona of processes around the optic disc. Over subsequent days, astrocytes extended over the retina, covering approximately 35% of the retina at birth (typically E21-22) and reaching the edge of the retina by P(postnatal day)8. As they spread, astrocytes were closely associated with the developing vasculature, spreading ahead of patent vessels by a small but distinct margin. The most peripheral astrocytes assumed a bipolar morphology and extended processes towards the margin of the retina. Astrocytes nearer the optic disc showed the stellate shape characteristic of mature cells. The appearance of astrocytes at the optic disc at E18, 2 days after the appearance of type-1 astrocytes in the optic nerve (Miller et al.: Dev. Biol. 111:35-41, '85), suggests that retinal astrocytes may be type-1 astrocytes generated in the optic nerve. Watanabe and Raff (Nature 332:834-837, '88) have recently reported an independent study supporting the same conclusions.
Aging↗
Extracellular space in the developing retina assessed by electron microscopy: laminar and topographic distribution.
The extent of extracellular space (ECS) in the developing retina of the cat has been measured by electron microscopy in material fixed using techniques developed by others to preserve ECS. ECS is generally greater in foetal than in adult material. It is particularly marked in the plexiform layers of retina at the time of synaptogenesis and in the axon layer at the time of axon growth. The changes in ECS occur first in the central retina, and spread to the periphery. These observations suggest that the high volumes of ECS found in the foetus are not artefactual, but accompany and may play a role in developmental processes.
Aging↗
Idiopathic recurrent pancreatitis. An approach to diagnosis and treatment.
The cause of recurrent acute pancreatitis can be identified in the majority of patients. A small group of patients in whom an etiological association is not obvious is characterized as idiopathic recurrent pancreatitis (IRP). During the last seven years, we used endoscopic retrograde cholangiopancreatography (ERCP) and sphincter of Oddi (SO) manometric pressure studies to investigate 116 patients initially diagnosed as IRP. Forty-four of the 116 patients were found to have a demonstrable cause of their pancreatitis. Appropriate therapeutic intervention was carried out in 43 of these patients with a favorable outcome in the majority of patients noted during long-term follow-up.
Cholangiopancreatography, Endoscopic Retrograde↗
Tissue penetration and pharmacokinetics of lomefloxacin following multiple doses.
The pharmacokinetics of lomefloxacin were studied after three days of oral administration of 400 mg/day lomefloxacin. Following the final dose the concentrations in serum, urine and cantharidin-induced inflammatory fluid were measured by a microbiological assay. The mean peak serum level was 4.9 mg/l at a mean time of 0.8 h. The mean serum elimination half-life was 6.2 h. The mean maximum inflammatory fluid level attained was 3.2 mg/l at 2.7 h. Urinary recovery accounted for the greater part of lomefloxacin's elimination.
4-Quinolones↗
Interferon-gamma-treated K562 target cells distinguish functional NK cells from lymphokine-activated killer (LAK) cells.
In vitro incubation of the erythroleukemic cell line K562 with interferon-gamma (IFN-gamma) renders these cells relatively resistant to natural killer (NK) cell lysis. However, such treatment does not alter their sensitivity to LAK cell lysis. Thus, the lytic susceptibility of interferon-gamma-treated K562 (I-K562) cells to LAK cells as opposed to its relative resistance to NK cell lysis provides a functional assay to help distinguish these two types of effector cells. The relative resistance of I-K562 for NK cell-mediated lysis was not secondary to the release of soluble factors or the frequency of Leu-19+, CD3+ T cells, residual IFN-gamma, or expression of MHC Class I molecules. Coincubation of I-K562 cells with NK or LAK cells overnight did not appreciably change the pattern of lytic responses against K562 and I-K562 target cells. However, incubation of PBMC in vitro with I-K562 but not native K562 in the presence of r-IL-2 leads to a marked decrease in the generation of LAK cells. The inhibition of LAK cell generation was not secondary to differences in the consumption of bioactive levels of IL-2. Differences in the lytic capability of NK and LAK effector cells suggest heterogeneity among cells that mediate such non-MHC-restricted lysis. Use was made of cells from a patient with a large granular lymphocyte lymphoproliferative disease (greater than 85% Leu-19+) to determine if such cells could be used to distinguish clonal population of cells which would represent NK or LAK cell function. Of interest was the finding that such cells, even after incubation in vitro with IL-2, showed lytic function representative of NK cells but not LAK cells. Data concerning the inhibition of LAK cell generation by I-K562 cells have important implications for future therapeutic trials of IFN-gamma and IL-2 in the treatment of human malignancies.
Antigens, Differentiation↗
The appearance and distribution of microglia in the developing retina of the rat.
We have examined the development of microglia in the rat retina, using a peroxidase-conjugated lectin derived from Griffonia simplicifolia. Retinas were studied from animals aged from E(embryonic day)12, just after the invagination of the optic cup and prior to the closure of the optic fissure, to adulthood. The lectin also proved a sensitive label for the endothelial cells of the developing retina. Our results provide some support for the view that microglia are derived from the monocyte-macrophage series of blood cells. At E12, most labeled cells were found at the vitreal surface, suggesting that they had come from the hyaloid circulation, while some had entered the retina and appeared to be migrating towards its ventricular surface. From E14 to early postnatal ages, most labeled cells had processes and resembled the amoeboid microglial cells described in silver carbonate staining studies (Ling, 1982). The number of labeled cells rose from about 700 to E14 to a peak of about 27,000 at P(postnatal day)7, and fell to about 19,600 by P12. As early as E16, a regularity was apparent in the distribution of microglial cells over the surface of the retina, the cells tending to avoid each other. Microglial cells are found throughout the thickness of the very young retina, but as the layers of the retina differentiate, they are increasingly restricted to the inner half of the retina. Our findings indicate that microglia enter the retina well before the period of neuronal death, making it unlikely that they invade the retina solely in response to cell death. Our results confirm however that, once in the retina, microglia become associated with, and appear to phagocytose, the pyknotic debris which appears during the period of neuronal death. They also become closely associated with the retinal vasculature. In the adult, the intensity of the labeling of microglia was much reduced. Those cells which were labeled appeared more differentiated, resembling the "resting microglia" described in earlier studies.
Animals↗
Reduced selenium status of patients with asthma.
1. Selenium is an essential component of glutathione peroxidase (GSH-Px, EC 1.11.1.9), an enzyme which helps protects cells against damage caused by free radicals and hydroperoxides. 2. We report the plasma, whole blood and platelet concentrations of selenium, and whole blood and platelet activities of GSH-Px, in 49 patients with asthma, 23 of whom had coexisting eczema, and 76 healthy control subjects. 3. The asthmatic patients had significantly lower concentrations of selenium measured in plasma (P less than 0.001) and whole blood (P less than 0.001), but not in platelets. When the data were summarized as odds ratios there was a highly significant 3.54- and 5.08-fold increased probability of asthma observed for the lower range of plasma and whole blood selenium concentrations, respectively. 4. No overall decrease in platelet or whole blood GSH-Px activity was found when the asthmatic and control groups were compared. 5. Although patients with symptomatic asthma have a reduced selenium status, this does not appear to influence the antioxidant capacity of their circulating blood cells.
Adolescent↗
Pseudoepidemic of urinary tract infections due to Trichosporon beigelii.
During the period April, 1985 to March, 1986, Trichosporon beigelii was isolated from the urine of 15 intensive care unit patients. All of these patients had Foley catheters in place at the time of T beigelii isolation. None of them had urinary tract infections on admission, and it was initially felt that this organism was a source of infection in these critically ill individuals. Subsequent investigation revealed this to be a pseudoepidemic secondary to contamination of the urinary catheter drainage system. Urine obtained by gravity drainage from the outlet port of urimeters yielded growth of T beigelii, whereas urines obtained concurrently from the proximal tubing sampling port were negative. T beigelii was isolated from the drainage port as well as from various items used in the collection and sampling of urine specimens. It is felt that these items were the source of perpetuation of this pseudoepidemic due to the repeated contamination and colonization of the distal portion of the urine catheter collection system. In-services to nursing and housekeeping personnel in the proper collection of urine specimens and cleaning of potentially contaminated items, the replacement of metal urine graduates with disposable plastic ones and increased monitoring of personnel's activities stopped the outbreak abruptly.
Catheters, Indwelling↗
Topography of the retina in the elephant Loxodonta africana.
The distribution of neurones in the ganglion cell layer of the retina of an African elephant is described. The eye was obtained post-mortem from an infant animal, which died of an unknown disease. It is assumed that most of the neurones observed in the ganglion cell layer are ganglion cells. Ganglion cells concentrate along a horizontal axis extending across the retina inferior to the optic disc, as in the visual streak described in the retina of many mammals. They also concentrate in the upper temporal retina, in a pattern distinctive to elephants. We suggest that this latter concentration has evolved to monitor the animal's trunk. Features of the eye, including its size, orientation and fundal pigmentation, are also described.
Animals↗
Depression following spinal cord injury. A prospective in-patient study.
In a systematic prospective study of 71 patients with acute spinal cord injury carried out in the acute and rehabilitation phases of treatment, 14 patients meeting the DSM-III criteria for major depressive disorder were identified. A further 13 patients had transient periods of depressed mood, while the majority of patients showed no clear evidence of depression. The BDI was found to be valid in this group of patients.
Adjustment Disorders↗
The development of astrocytes in the cat retina: evidence of migration from the optic nerve.
To test recent ideas of the origin of retinal astrocytes we have studied the distribution of astrocytes, identified by anti-GFAP antibodies, in the developing retina of the cat. GFAP+ cells first appeared at the optic disc at E53 (embryonic day 53). At subsequent ages, GFAP+ cells covered successively larger regions surrounding the optic disc, and were found at the edge of the retina by P35 (postnatal day 35). During development, the GFAP+ cells near the optic disc were strongly related to blood vessels and axon bundles; in a more peripheral zone they were closely associated with the immature capillary net; while the most peripheral GFAP+ cells appeared to extend exploratory processes towards the margin of the retina. The velocity at which the 'front' of GFAP+ cells spread over the retina was estimated at 170-240 microns/day. At no time during development were GFAP+ cells observed in the area centralis. Except at the area centralis, the spread of GFAP+ cells preceded the formation of capillaries, by a small but distinct margin. GFAP+ cells also extended for a short distance from the optic disc along the proximal part of the hyaloid artery. These results support the view that retinal astrocytes migrate into the retina from the optic disc, in close association with the formation of retinal vasculature.
Animals↗
Time course of stratification of the dendritic fields of ganglion cells in the retina of the cat.
The inner plexiform layer (IPL) of the retina has been shown by previous workers to comprise a number of sublayers (sublaminae or strata), each containing a distinct component of its circuitry. Using horseradish peroxidase applied to cultured whole retinas, we have observed the segregation of the dendrites of ganglion cells of the cat retina into two sublayers of the IPL. These sublayers appear to correspond to the a and b sublaminae described in studies of the adult IPL. As the dendritic fields of ganglion cells form, in mid-gestation, they are diffuse, spreading through the ganglion cell and inner plexiform layers. A few weeks before birth the dendrites become restricted to the IPL, but it is not until after birth, between P(postnatal day)2 and P5, that they segregate into inner and outer sublayers of the IPL. The process of segregation may involve the loss or 'pruning' of excess dendrites formed in 'wrong' sublayers. The segregation of dendrites into sublayers occurs concurrently with the formation of synapses by bipolar cells and may be induced by contacts made by bipolar cells onto the dendrites of ganglion cells.
Aging↗
Catecholaminergic and cholinergic neurons in the developing retina of the rat.
We have examined the development of catecholaminergic and cholinergic neurons in the retina of the rat by using antibodies against the enzymes tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT), respectively. TH-immunoreactivity was first detected at P (postnatal day) 3 in somata located in the inner part of the cytoblast layer (CBL) and in fine dendrites extending toward the middle of the inner plexiform layer (IPL). These cells were similar in shape and soma size to the class 2 TH-immunoreactive (TH-IR) cells of the adult rat. At P6, TH-immunoreactivity was expressed by a second population of cells. Their somata were in the inner part of the inner nuclear layer (INL), but were distinctly larger, with short thick dendrites extending into the outer and/or middle parts of the IPL. Over subsequent days, the dendrites of these larger cells spread profusely in the outer part of the IPL, making it likely that they are the class 1 TH-IR cells of the adult. ChAT-immunoreactive (ChAT-IR) cells were not detected until P15, when ChAT-IR somata were observed in the ganglion cell layer (GCL) and INL, and their dendrites were observed already segregated into the distinct strata of the IPL in which they are found in the adult. The subsequent growth of TH-IR somata of both classes was uneven, persisting longer in temporal than in nasal retina. This extended growth of temporal cells establishes the marked nasotemporal differences in soma diameter apparent among TH-IR cells in the adult (Mitrofanis and Stone, '86; Mitrofanis et al., '88b). The growth and adult size of ChAT-IR somata, on the other hand, did not vary with retinal position; their diameters were similar to those of the adult cells from the time they first appeared. The distribution of ChAT-IR cells at P15 shared several features of the distribution of ganglion cells. The density of ChAT-IR cells was greatest at the area of peak ganglion cell density and declined toward the periphery. In contrast, TH-IR cells concentrated from the time they first appeared at the superior temporal margin, peripheral to the area of peak density of ganglion and ChAT-IR cells.
Aging↗
The development of astrocytes in the albino rabbit retina and their relationship to retinal vasculature.
We have examined the development of astrocytes in the albino rabbit retina, using antibodies to glial fibrillary acidic protein (GFAP) and vimentin. Vimentin immunoreactive (vimentin+) astrocyte-like cells first appear at the 24th postconceptional day (24 PCD), in a pattern similar to that of the adult. GFAP immunoreactivity was first detected in astrocytes at the 29 PCD, in a similar pattern. Vessels enter the retina from 29 PCD. The presence of astrocytes in a mature distribution prior to the ingrowth of vessels indicates that astrocytes are not dependent on the vessels for their early positioning and differentiation. In contrast with the rat and cat, we found no evidence of migration of astrocytes into the rabbit retina from the optic nerve.
Aging↗
Helicopter transport of patients during acute myocardial infarction.
Initial experience with a regional system of emergency helicopter transport of patients with acute myocardial infarction (AMI) referred for emergent cardiac catheterization and percutaneous transluminal coronary angioplasty (PTCA) is described. Two hundred fifty patients with AMI were transported from within a 150-mile radius to Duke University Medical Center over a 15-month period. All patients were within 12 hours of onset of symptoms. Thrombolytic therapy was administered to 240 (96%) patients (72% before or in-flight). The time to administration of thrombolytic therapy ranged from 30 to 120 minutes (median 180), while the time to arrival in the interventional catheterization laboratory ranged from 105 to 815 minutes (median 300). The flight time was 12 to 77 minutes (median 31). Most patients had 1- or 2-vessel coronary artery disease; the baseline ejection fraction ranged from 27 to 70% (median 42). Transient hypotension was the most common complication both pre-flight and in-flight. Third-degree atrioventricular block and nonsustained ventricular tachycardia were the next most common complications. Ventricular fibrillation or sustained ventricular tachycardia occurred before takeoff in 38 patients (15%). No patients had ventricular fibrillation, asystole or respiratory arrest during transport. Fluid boluses for hypotension were the most common intervention. Five patients required cardiopulmonary resuscitation in-flight; 3 before lift-off and 2 required a brief period of cardiopulmonary resuscitation during sustained ventricular tachycardia. Fourteen patients had pressor therapy, military antishock trousers or both to maintain adequate blood pressure. Neither cardioversion, defibrillation nor intubation were performed in-flight. Thus, inflight complications are infrequent and can be managed en route to an intervention center.(ABSTRACT TRUNCATED AT 250 WORDS)
Aircraft↗