Serum beta 2 microglobulin and C-reactive protein in the monitoring of lymphomas: findings in a multicenter study and experience in selected patients.
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Biomedical subjects
Publications and source records attributed to J Stone.
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Two major conceptual approaches to the study of visual receptive field physiology can be identified; one, here termed the 'parametric' approach, which considers all the properties of a cell to be potentially related to that cell's functional role, and a second, here termed the 'feature extraction' approach, which regards a particular receptive field property as defining a cell's role in the visual system. The parametric approach seems most compatible with network theories of visual information processing, while the feature extraction approach suggests a localized single-cell form of visual representation. In this paper we trace the growth and development of these two approaches, from 1938 to the present, by dividing this period into four segments: 1938--1953, during which the foundations of both approaches were laid; 1953--1966, the major period of growth for feature-extraction analyses; 1966--1975, the major period of growth for parametric analyses; and 1975 to the present, during which the parametric approach has been expanded by the incorporation of principles of systematics and population biology to enable groups of neurones to be studied from a biological perspective.
Within any biological population there is considerable variation in the physical characteristics of individual members, and the understanding and classification of such populations always depends on the interpretation of this variation. A major point of this paper is that groups of neurones can also be regarded as biological populations, and that at least three distinct types of variation can be found within any neural population:role-indicating variation, which enables different cells or groups of cells to perform different functions; systematic variation, which allows different cells (or sometimes the same cell) to perform a particular function under varying conditions; and residual variation, which is principally related to mechanisms of evolution and provides the population with its biological adaptability. Examples of these three types of variation are suggested for a number of properties of retinal ganglion cell populations. A second major point is that any functional classification of nerve cells should contain multiple taxonomic levels, corresponding to different levels of complexity and interaction within the nervous system. Thus, individual cells can belong to more than one group, each at a different taxonomic level, and these groups of cells can be viewed as interacting with each other rather than as operating in isolation. A multiple-level classification of cat retinal ganglion cells is presented with two broad groups, each subdivided into two lower-level groups, and an attempt is made to identify the categories of visual function to which these groups are related.
We have developed and characterized a method for the rapid detection and quantitation of specific DNAs in partially purified extracts of single Drosophila. While the method should be applicable to a number of repetitious DNA sequences, we have used the polypyrimidine DNA sequences (TCTCT)n to develop this technique. Using hydroxyapatite chromatography, we were able to measure the amount of nucleic acid hybrid formed and to obtain a thermal elution profile of the hybrid formed in extracts of single flies. Under a variety of conditions, purified DNA and DNA in partially purified extracts gave essentially identical results. The procedure can be used to detect the presence of rare sequences, or to measure the relative abundance of a prevalent DNA species. 40 different wild type strains of Drosophila melanogaster were examined using this technique and all contain similar amounts of the same polypyrimidine/polypurine sequence. From a small scale screening of different laboratory stocks of D. melanogaster, a variant was found which formed more DNA-DNA hybrid with labelled polypyrimidine tracts than did wild type. The additional hybrid was distinguished by a lower thermal stability than the hybrid formed in wild type.
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The morphology of catecholaminergic cells of the cat's retina was studied by fluorescence microscopy of retinal whole mounts. Although varied in soma shape, these cells seem to represent a single group of cells with an average soma diameter of 14.5 micrometer in freeze-dried material. The fluorescent terminals of these cells formed a striking two-dimensional pattern: a significant portion of them appeared to be arranged in rings located at the boundary of the inner plexiform and inner nuclear layers. The mean diameter of these rings was 9.7 micrometer and their pattern appeared to extend unbroken across the retina. It was, in general, not possible to observe the connection between these rings and fluorescent somas, except when a ring was in a juxtasomatic position. It is suggested that the postsynaptic somas within these rings are either of other amacrines or of interplexiform cells. Using the Golgi-Colonnier technique on retinal whole mounts, an attempt was made to identify the cell type which resembles the catecholaminergic cell in its size, location and morphology. The suggested cell type appears to be among the largest amacrine cells, (mean soma size of 11.5 micrometer in Golgi material) with a considerable dendritic network at the border of the inner plexiform and inner nuclear layers, although there are branches reaching as far as the middle of the inner plexiform layer.
Persistent pain at the site of injection is the most common complication of local anesthesia in the oral cavity. The complication of trismus after local anesthetic injection is rare and may be prevented by the use of short needles for maxillary posterior injections, and by the avoidance of multiple injections in a short period time. Once trismus develops, its progression to chronic hypomobility and fibrous ankylosis may be prevented by the early institution of treatment consisting of heat, analgesics, muscle relaxants, and exercises.
We argue that it seems fruitful to regard the retino-geniculate-cortical pathway, and perhaps the visual pathways in general, as comprising distinct neuronal channels which begin with the major groupings of ganglion cells, and subserve distinct functions within the overall operation of the visual system. One problem for future work is to determine the extent and, equally importantly, the limitations of the idea of independently functioning neuronal channels operating within the visual system. Some evidence of those limitations is already available. Kulikowski and Tolhurst have provided evidence suggesting that pattern detection is mediated by the X-like system at high spatial frequencies and by the Y-like system at low frequencies, but that at intermediate frequencies, both systems are likely to contribute to this function. Again, there is already physiological and psychophysical evidence of inhibitory interaction between X- and Y-cell systems, which may contribute to their functioning. That is, although there is little evidence of excitatory interaction between W-, X- and Y-cell systems, at least up to the first cortical synapse, the functioning of, say, the X-cell system may depend on the inhibitory influences impinging on it from Y-cell activity. Further, it may prove to be the case that one cell 'system' may be involved in several distinct functions and considerable work may be required to establish whether or not these functions can be considered constituent parts of an overall function, such as 'ambient' or 'foveal' vision. In the following section we suggest a classification and terminology for visual neurones which may provide a framework for future work on these lines.
The origins of brain stem projections to the cytoarchitectonically different areas 17, 18 and 19 of the cat's visual cortex were studied following small horseradish peroxidase (HRP) injections. Labelled cells were counted in a dopaminergic nucleus (nucleus linearis rostralis (NLR)), other catecholaminergic nuclei (locus coeruleus, parabrachialis nuclei and nucleus subcoeruleus) and serotonergic nuclei (nucleus raphe dorsalis (NRD) and nucleus centralis superior (NCS)). Area 18 receives afferents from more locus coeruleus cells than either of areas 17 or 19. The number of labelled cells in the catecholaminergic nuclei far exceeds that in the serotonergic nuclei.
Estracyt, a conjugate of an alkylating agent with an oestrogenic sterol, was given in a dose of 420 mg daily to a group of 44 postmenopausal patients with very advanced breast carcinoma. Thirty-eight of these were in relapse following chemotherapy and 32 had evidence of distant metastases. Seventeen patients had an objective response and marked or complete alleviation of symptoms, four others had a useful symptomatic response but no beneficial effect was observed in the remainder. Three who had shown no response to previous oestrogen therapy also failed to respond to Estracyt as did all nine patients with hepatic metastases. Oestrogen receptor status and age within the postmenopausal group seemed to have no bearing on the result. Side-effects were minimal with nausea in 18 patients but in only two did this necessitate withdrawal of the drug. Bone marrow depression did not occur. Changes in acute-phase reactant proteins suggested that part of the Estracyt was de-esterified in the liver liberating oestrone but the low incidence of vaginal haemorrhage and the recalcification of bony metastases suggested that on the whole Estracyt behaves as an anti-oestrogen as well as an antimitotic.
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We surveyed 101 different Drosophila species for the presence of a particular highly repetitive DNA sequence containing long tracts of polypyrimidine/polypurine DNA, first found in D. melanogaster. Out of 55 tested species in the melanogaster group, only the sibling species D. simulans and D. mauritiana, as well as one distant relative in the ananassae subgroup, D. varians, contained the same sequence. All four of these species have long pyrimidine tracts as shown by acid hydrolysis of labelled DNA. All four species have the same sequence, bu the amount of this polypyrimidine/polypurine DNA varies greatly. Four other species in the hydei subgroup were found to contain a polypyrimidine/polpurine sequence, with an oligonucleotide composition different from that of D. melanogaster. This polypyrimidine DNA varies from as much as 10% of the total DNA in D. nigrohydei, to as little as 0.4% in D. neohydei. The long pyrimidine tracts in the hydei subgroup are often more than a thousand nucleotides in length, representing exceedingly homogeneous repetitious sequences.--These results show a rapid but discontinuous pattern of evolution for polypyrimidine/polypurine DNA . These sequences are not species specific, yet closely related species have greatly different amounts of polypyrimidines. Drastic changes occur in the amounts of these satellite type DNA sequences, as if the sequence had no continuous selective advantage in evolution. The implications of these results with regard to the general function and evolution of satellite DNA are discussed.
This essay is in two parts. In the first part, consideration is given to specific issues raised in the preceding article, stressing two considerations. First, although Dr. Hughes disclaims an essentialist position, he in fact argues consistently for a classification of nerve cells based on key, essential features; except where, briefly, he argues for a numerical taxonomic approach. He apparently has not understood the hypothetico-deductive approach proposed by us. Second, he has not given consideration to important biological aspects of the problem of cell classification, in particular to the significance of variation of properties both within groups of cells and between corresponding groups. In the second part we argue that underlying the exchange of specific criticisms are differences in scientific methodology. We attempt to identify these differences, and to relate them to the present discussion. We hope that this will help focus subsequent discussion on the central issues involved and we argue for increased awareness on the part of neurobiologists of our own presuppositions about how science works.
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The number of ganglion cells in the cat's retina, and the pattern of their distribution over the retina, have been reinvestigated. Criteria are presented for the identification of ganglion cells in Nissl-stained whole mounts, most particularly for the distinction between small ganglion cells and neuroglial cells, by reference to retinas with no ganglion cells (obtained by nerve section) and to areas to retina containing a population of only small ganglion cells (obtained by optic tract section). Using these criteria, the number of ganglion cells was counted in four retinas (mean total 116,250). The number of large or "giant" cells (presumably the somas of Y-cells and of alpha-cells) varied from 4,200 to 7,100. Overall these cells comprised 4.0-6.3% of the total ganglion cell population. Their distribution over the retina showed a concentration around the area centralis, with a localized minimum density at the area centralis, and a concentration in the visual streak. These concentrations of large cells were quantitatively less than the concentrations of smaller cells in the area centralis and visual streak, so that the relative frequency of large cells was minimal (mean 1.6%) at the area centralis and increased steadily up to 5.5-6.9% in peripheral retina. Their relative frequency was distinctly lower along the visual streak than in peripheral retina above or below the streak.
Ganglion cell density maps of the retinas of Siamese cats show the same major features of ganglion cell distribution as are found in normally pigmented cats, in particular the area centralis and visual streak. In the retinas of the seven Siamese cats investigated, however, the areas centralis was "underdeveloped" when compared with the normally pigmented cat. The peak ganglion cell density was lower and the ganglion cells usually larger than at the area centralis of the normally pigmented cat, and the characteristic blood vessel pattern around the area centralis was less developed. One animal showed a marked blood vessel abnormality, a vessel crossing the area centralis in each retina. In another animal, the distribution of ganglion cells appeared abnormal throughout the retina. Medium-sized, possibly X-type ganglion cells were lacking from all retinal areas, overall cell numbers were low and the distribution of ganglion cells showed a prominent visual streak.
By sectioning one optic tract in Siamese kittens and allowing sufficient time for the affected ganglion cells to degenerate and disappear, we have obtained maps of the distribution of ipsi- and contralaterally projecting ganglion cells in the retina of the Siamese cat. As previous work predicted, many ganglion cells in the Siamese cat retina project contralaterally which, in the normally pigmented cat, would project ipsilaterally. The transition from the pattern of projection typical of nasal retina (all contralateral) to that typical of temporal retina (most ipsilateral) is much more gradual in the Siamese cat than in the normally pigmented cat, and is centred 1.7-3 mm temporal to the area centralis, instead of at the area centralis. In the Siamese cat only a few ganglion cells at the area centralis project ipsilaterally, as against nearly 50% in the normally pigmented cat. The proportion of ipsi-projecting cells reaches the 50% level 1.7-3.0 mm into temporal retina, and overall the zone of transition may be several millimetres wide, as against about 0.2-0.5 mm in in the normall pigmented cat. Evidence is presented that the degree of the abnormality of nasotemporal division varies between individual Siamese cats and that the abnormality is more severe among large or "giant" cells than among the population as a whole.
The number of myelinated axons in the cat's optic nerve has been estimated from a partial count of sections of the nerve examined by electron microscopy. The average count obtained from four nerves was 128,600 (range 112,800-147,200). This figure is within 10% of a previous estimate of the number of ganglion cells in the cat's retina, but is 33% lower than the only previous estimate of the number of these axons based directly on electron microscopy. Possible sources of the discrepancy are discussed. The functional implications of this total, in the context of earlier work on ganglion cell topography, are also discussed.