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H Kennedy

Publications and source records attributed to H Kennedy.

At least 19 recordsLinked to original sources

Visuotopic organization of corticocortical connections in the visual system of the cat.

It has recently been demonstrated that, in contrast with the retinogeniculocortical projection, the corticocortical connections in the cat present a high degree of convergence and divergence. This suggests that some corticocortical connections link nonvisuotopically corresponding regions. Using fine-grain electrophysiological mapping and anatomical tracing, we have set out to test this possibility by placing a small injection of retrograde tracer in area 17 and by comparing the extent of visual field encoded in the region of area 18 containing labeled cells and that represented in the uptake zone. The results demonstrate that the size of the labeled region on the surface of area 18 is independent of eccentricity and that, despite its anisotrophy, this region of labeling encodes a broadly circular region of visual field that is larger than that encoded in the uptake zone of the tracer in area 17. For example, in the representation of lower visual field, a virtual point in area 17 that encodes a visual field region 4 degrees in diameter receives afferents from a region of area 18 encoding a region 11 degrees wide. Examination of the density of labeled cells in the labeled zone in area 18 reveals that the highest density is observed in a region in visuotopic correspondence with the injection site. However, high labeling density is also occasionally found in patches that do not represent the same visual field region as the injection site. Many receptive fields of neurons recorded in the labeled zone in area 18 only partially overlap or fail to overlap the visual field region encoded by the injection site. The results also demonstrate that the extent of visual field encoded in the labeled zone in area 18 is the same as that represented in the region of intrinsic labeling in area 17. It is suggested that cortical afferents coming from several cortical areas and converging on a column of cells in area 17 cover the same extent of visual field and that this cortical network constitutes the structural basis for the modulatory regions of the receptive field as well as the synchronization of neurons in different cortical areas.

Animals

Zinc absorption in adult men from a chicken sandwich made with white or wholemeal bread, measured by a double-label stable-isotope technique.

Eleven fasted adult men consumed a chicken meat sandwich made with white or wholemeal bread, extrinsically labelled with 2 mg 67Zn, on two different occasions. Immediately after eating the sandwich they were given an intravenous injection of 1.5 mg 70Zn. True Zn absorption (which was approximately 7% higher than apparent absorption) was determined by the faecal balance technique by making an allowance for endogenous excretion from measurements of faecal excretion of 70Zn. There was no significant difference in mean true Zn absorption from the white or wholemeal bread sandwich, 33.6 and 25.4% respectively. It was concluded that the substitution of wholemeal for white bread does not reduce Zn absorption from meat-based sandwiches.

Adult

International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B. II. Evaluation and selection of candidate reference materials.

The first phase of an international collaborative study for standardization of test systems for measuring apolipoprotein (apo) A-I and apo B demonstrated that uniformity of apo A-I and apo B measurements can be achieved if suitable common reference materials are used to calibrate the different systems. The objective of the second phase was to evaluate the linearity and parallelism or proportionality of the candidate reference materials selected in phase one and to determine whether any of them could be proposed as international reference materials. We evaluated the proposed reference materials with 37 test systems for apo A-I and 38 for apo B, involving 23 manufacturers and five research laboratories. Two lyophilized preparations were proposed for apo A-I, SP1 from Behringwerke AG and SP2 from Daiichi Pure Chemicals Co., and two liquid preparations were proposed for apo B, SP3 from Behringwerke AG and SP4 from Reagents Applications. The linearity of the candidate reference materials was compared with the linearity of a frozen serum pool or interim serum reference material distributed to all the participants and with that of a fresh serum pool prepared by each participant. SP1 and SP3 exhibited linearity and parallelism similar to that of the fresh frozen serum pool and had among-laboratory CVs less than or similar to those obtained on normolipidemic serum samples (approximately 6% for apo A-I and approximately 7% for apo B).

Apolipoprotein A-I

The effects of bilateral enucleation in the primate fetus on the parcellation of visual cortex.

Bilateral enucleation in the macaque fetus causes an areal reduction of an otherwise normal striate cortex. Here we show that in early operated animals this reduction is accompanied by a separation of striate and prostriate cortices which are normally contiguous. However this induced separation does not correspond to the areal reduction of striate cortex, indicating that extrinsic signals regulate either the proliferation and/or survival of striate cortical neurons.

Animals

Cost efficiency of bone scans in breast cancer.

A total of 110 consecutive females who presented in 1987 with primary carcinoma of the breast were staged according to the UICC TNM staging system. Of these, 90 patients had bone scans at presentation, of which seven were positive. The rate of positive initial scans for Stages I-II was 3.5%. Of these only one patient subsequently had bone metastases confirmed, to diagnose which by bone scan, the estimated cost was pounds 1300. Follow-up information was obtained for 95 patients, repeat scans being performed in 22 who had symptoms suggestive of bone metastases. Ten patients with negative initial scans converted to scan-positive within a mean time of 15 months. Only four of these had radiological confirmation of bone metastases. The cost of detecting bone metastases by follow-up scan was approximately pounds 80 per patient. The false-positive rate and the false-negative rate were both calculated as 10%. The specificity of the test was calculated as 90%. It is recommended that bone scanning should be reserved for patients with Stages III and IV disease and to evaluate symptoms suggesting bone metastases.

Adult

Reflections on the aim of child analysis.

Childhood disturbances can best be studied in a developmental frame of reference. Following Anna Freud, the authors distinguish between outcome aims and intermediary aims. They present the analyses of a child and an adolescent to demonstrate how these aims affect the nature and progression of treatment.

Adolescent

Segregation of callosal and association pathways during development in the visual cortex of the primate.

The segregation of callosal and association pathways in the developing visual cortex of the monkey was studied using the retrograde tracers fast blue and diamidino yellow. Quantitative analysis of the laminar distribution of labeled callosal and association neurons made it possible to reveal the shifting pattern of connections that characterizes the development of these two pathways. In the adult, callosal neurons are restricted to supragranular layers, where they are concentrated at the bottom of layer 3. Association neurons are located both in infra- and supragranular layers. Supragranular layer association neurons are concentrated in layer 2, with limited spread into layer 3 so that there is little overlap with callosal neurons. In the immature brain, callosal neurons are characterized by a tangential distribution that is more widespread than in the adult, while their laminar distribution undergoes little developmental change. Association neurons show two types of changes in their laminar distribution: (1) in the early fetus, there is a large excess of association neurons in supragranular layers, the adult distribution being achieved some time after birth; and (2) during maturation there is a selective elimination of at least 50% of the projections originating from the lower part of layers 2/3. Hence, the adult radial segregation of association and callosal pathways is achieved in part by regressive phenomena. The developmental reduction of bihemispheric projections is largely independent of changes in the organization of association neurons. Quantitative analysis of the morphology and spatial location of neurons sending axon collaterals to both hemispheres suggests that they constitute a subset of callosal neurons and that their frequency is determined by factors that regulate directly this population. These results are discussed with respect to the specification of visual cortical pathways during ontogenesis.

Amidines

Incidence of visual cortical neurons which have axon collaterals projecting to both cerebral hemispheres during prenatal primate development.

Fast blue was injected massively in extrastriate cortex of one hemisphere Diamidino yellow in area 17 of the other hemisphere, in adult and prenatal cynomolgus monkeys. After a suitable survival period the brains were processed for fluorescent dyes. Counts were made of the total number of labeled neurons and of those neurons which were labeled by both dyes and which project therefore to both hemispheres by means of bifurcating axon collaterals. At 122 and 135 days after conception (E122 and E135), shortly after cortico-cortical pathways are established, double-labeled neurons constituted 0.45% and 0.46% of the total population of labeled neurons in area V2. In V2 in the adult the range of values of double-labeled neurons was 0.03-0.08%.

Animals

Convergence and divergence in the afferent projections to cat area 17.

We have examined the topography of the afferent connections to area 17 in the cat by means of double retrograde label tracing techniques. Injections of two fluorescent retrograde tracers, diamidino yellow and fast blue, were made with variable separations in area 17 and the spatial distributions of the resulting populations of labeled cells examined in afferent cortical areas and subcortical structures. When injections were separated rostrocaudally, the topographic organizations of the projections were characterized quantitatively with two graphic methods: the labeling density curve and the connectivity graph. The labeling density curve measures labeled neuron density in successive rostrocaudal sections, whereas the connectivity graph provides a two-dimensional model of the topography of a given connectivity. The connectivity graph makes it possible to define two parameters that characterize the topography of the connection: the convergence and the divergence. The convergence is defined as the extent of an afferent structure that contains neurons converging on a line normal to the cortical surface in area 17. The divergence is the extent of area 17 that is innervated by neurons contained in an infinitely small region of the afferent structure. The results show that a number of subcortical structures project to area 17 in a nontopographic manner, i.e., that in each of these structures neurons contained in an infinitely small region send projections to the whole of area 17 and that a line normal to the surface of area 17 is innervated by neurons distributed throughout the afferent structure in question. Nontopographic projections are found from the intralaminar nuclei, the ventral mesencephalic tegmental region, the diagonal band of Broca, and the locus coeruleus. All remaining subcortical structures and cortical areas send topographically organized projections to area 17. The extent of the convergence and divergence, however, varies between structures. Only the projection from the A laminae of the LGN was found to approximate a point-to-point projection with a convergence of 0.4 mm and 2 mm in divergence. Much larger convergence and divergence values are found in the projections from the claustrum and the cortical areas. For example, the divergence reaches 20 mm for the projections from area 20 or from the anterior part of the lateral suprasylvian sulcus. Knowing the convergence and divergence values and the retinotopic organizations of area 17 and a number of its afferents, it becomes possible to test whether connections in the visual system link regions representing the same zone of the visual field.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways

Maturation and connectivity of the visual cortex in monkey is altered by prenatal removal of retinal input.

In several species, the peripheral input from the eyes partly determines the pattern of interconnections between the visual areas of the two cerebral hemispheres through the fibre tract termed the corpus callosum. In the macaque monkey, the neurons projecting through the callosum are largely restricted to area 18 throughout ontogeny, whereas area 17 is characterized by few or no callosal projections. Here, we show that suppressing the peripheral input by prenatal removal of the eyes leads to a marked reduction in the extent of area 17, resulting in a large shift in the position of the histologically identifiable boundary between the two areas. Even so, the boundary continues to separate an area rich with callosal connections (area 18) from one poor in such projections (area 17), indicating there is no effect on the callosal connectivity of area 17. In contrast, in area 18, eye removal results in many more neurons with callosal projections than in normal animals. The results suggest that the factors that determine the parcellation of cortical areas also specify their connectivity.

Animals

A double-labeling investigation of the pretectal visuo-vestibular pathways.

The projections of the nucleus of the optic tract were studied in the cat by simultaneous use of two distinct retrograde tracers (Fast Blue and Diamidino Yellow) injected in the inferior olive and the prepositus hypoglossi nucleus. Following injections of diamidino yellow in one structure and fast blue in the other, a significant number of retrogradely labeled neurons projecting to either target were observed dispersed in the nucleus of the optic tract. Three populations of labeled cells were found: one which projected to the inferior olive, a second to the nucleus prepositus hypoglossi, and a third which projected by means of a bifurcating axon to both of these structures. Quantification of these results reveals that 72% of the total number of labeled neurons are labeled by the IO injection, the remaining cells being labeled by the NPH injection. Double-labeled neurons represent more than 7% of the total number of the labeled cells. Tentative inferences as to the electrophysiological properties of the nucleus of the optic tract are discussed in the context of the optokinetic system.

Amidines

Transient projection from the superior temporal sulcus to area 17 in the newborn macaque monkey.

Area 17 in the neonate of numerous species receives projections from cortical areas that do not project to area 17 in the adult. To investigate if this were the case in the developing primate, we have made injections of retrograde tracers in area 17 of newborn monkeys (Macaca irus) and examined the areal distribution of labeled neurons. Neurons projecting to area 17 were found to be restricted to those cortical regions that project to area 17 in the adult. The projection to area 17 in the neonate did appear to be very different in that in the superior temporal sulcus there was a large contingent of labeled neurons in supragranular layers. This constitutes a transient projection because in the adult area 17 projecting neurons in this cortical region originate almost exclusively from infragranular layers. To test if a change in the laminar distribution of area 17 projecting neurons in extrastriate cortex is a general feature of postnatal development, we have computed in neonates and adults the proportion of area 17 afferent neurons in infra- and supragranular layers for each cortical region that projects to area 17. This revealed (i) that in the adult the laminar distribution of area 17 afferents is characteristic for each cortical area and (ii) that this distribution emerges during development from an immature state in which labeled neurons are more numerous in supragranular layers. These results show that there is an extensive remodeling of the neuronal circuitry connecting visual cortical areas during postnatal development in the monkey and that the transient connectivity of primate area 17 is very different from that observed in other mammalian species.

Aging

Studies on calcium absorption from milk using a double-label stable isotope technique.

Calcium absorption was measured in ten male volunteers from skimmed milk, Ca-enriched skimmed milk or watercress (Nasturtium officinale) soup. The foods were labelled extrinsically with 30 mg 44Ca. Shortly after consuming the labelled meal, each subject was given an intravenous injection of 3 mg 42Ca. Fractional absorption from the oral dose was determined from plasma and urine samples collected 24-72 h later, using fast atom bombardment mass spectrometry to measure isotope ratios. The values for urine and plasma were in good agreement. Mean percentage absorption was 45.5 (SEM 1.9)% from the skimmed milk, 35.7 (SEM 4.7)% from the Ca-enriched milk and 27.4 (SEM 1.9)% from the watercress soup. The effect of consuming 568 ml (1 pint) Ca-enriched milk each day for 4 weeks on the efficiency of absorption of Ca was studied. Although there was no statistically significant difference between Ca absorption before and after the supplementation period, the results were considered to be somewhat inconclusive due to the small number of subjects and wide individual variation in Ca absorption.

Absorption

Characterization of transient cortical projections from auditory, somatosensory, and motor cortices to visual areas 17, 18, and 19 in the kitten.

We have examined the anatomical features of ipsilateral transient cortical projections to areas 17, 18, and 19 in the kitten with the use of axonal tracers Fast Blue and WGA-HRP. Injections of tracers in any of the three primary visual areas led to retrograde labeling in frontal, parietal, and temporal cortices. Retrogradely labeled cells were not randomly distributed, but instead occurred preferentially at certain loci. The pattern of retrograde labeling was not influenced by the area injected. The main locus of transiently projecting neurons was an isolated region in the ectosylvian gyrus, probably corresponding to auditory area A1. Other groups of transiently projecting neurons had more variable locations in the frontoparietal cortex. The laminar distribution of neurons sending a transient projection to the visual cortex is characteristic and different from that of parent neurons of other cortical pathways at the same age. In the frontoparietal cortex, transiently projecting neurons were located mainly in layer 1 and the upper part of layers 2 and 3. In the ectosylvian gyrus, nearly all the neurons are located in layers 2 and 3. In addition, a few transiently projecting neurons are found in layer 6 and in the white matter. Transiently projecting neurons have a pyramidal morphology except for the occasional spindle-shaped cell of layer 1 and multipolar cells observed in the white matter. Anterograde studies were used to investigate the location of transient fibers in the visual cortex. Injections of WGA-HRP at the site of origin of transient projections gave rise to few retrogradely labeled cells in areas 17, 18, and 19, demonstrating that transient projections to these areas are not reciprocal. Although labeled axons were found over a wide area of the posterior cortex, they were more numerous over certain regions, including areas 17, 18, and 19, and absent from other more lateral cortical regions. Transient projecting fibers were present in all cortical layers at birth. Plotting the location of transient fibers in numerous sections and at all ages showed that these fibers are not more plentiful in the white matter than they are in the gray matter. We found no evidence that the white/gray matter border constituted a physical barrier to the growth of transient axons. Comparison of the organization of this transient pathway to that of other transient connections is discussed with respect to the development of the cortex.

Aging

Absence of interhemispheric connections of area 17 during development in the monkey.

Our understanding of the development of cortical connectivity largely stems from studies of the ontogeny of interhemispheric pathways in carnivores, rodents and lagomorphs. Early in development, cortical neurons projecting to the contralateral hemisphere through the corpus callosum (callosal projection neurons) have a widespread distribution. As maturation proceeds, callosal projection neurons become restricted to those cortical regions that are connected in the adult. In newborn cats and rats, for example, callosal projection neurons are not restricted to the 17-18 border as in the adult, but are found throughout areas 17 and 18. The macaque monkey is an exception, because at birth it has an adult-like distribution of callosal projection neurons in area 18, with practically none in area 17. Here we show that whereas area 17 is devoid of interhemispheric connections throughout prenatal development, the distribution of callosal projection neurons in area 18 shows the common sequence of an early widespread distribution followed by regression. The absence of callosal projection neurons in area 17 throughout ontogeny may well be a feature unique to Old World primates.

Animals