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PubMedDate not supplied

Results of a preliminary study of the potential of vasodilators for improving thermotherapy of deep-seated tumours [printed with original paging at end of 2(2); omitted from Int J Hyperthermia 1986 Jan-Mar;2(1)].

Administration of the vasodilator hydralazine to a single mongrel dog with a transplanted, superficial transmissible venereal tumour in the abdomen permitted tumour-adjacent normal tissue temperature differences produced in local hyperthermia to be enhanced by nearly 2 degrees C. A preliminary study of tumour and normal tissue perfusion rate in the dog, employing the 15O-labelled water-positron emission tomography technique, suggested that administration of the vasodilator led to a significant reduction in the tumour perfusion rate, consistent with the observed tumour temperature enhancement. Computational studies with a multi-layer, one-dimensional cylindrical model of deep-tumour heating suggest that vasodilator-induced reductions of tumour perfusion rates could significantly increase deep tumour-superficial normal tissue temperature differences produced in deep-tumour thermotherapy.

Animals↗
PubMed2004

Enhanced wet deposition estimates using modeled precipitation inputs.

Effective assessments of linkages between atmospheric deposition and sensitive aquatic and terrestrial ecosystems require a knowledge of spatial patterns in deposition of greater resolution than currently available using point estimates and two-dimensional surface algorithms. A high resolution wet deposition model was developed for the Eastern U.S.A. by incorporating daily precipitation measurements from National Oceanic and Atmospheric Administration (NOAA) monitoring sites located within the Eastern U.S.A.; topographic variables, including elevation, slope, and aspect that affect the amount and distribution of precipitation across the region; and precipitation chemistry data from National Atmospheric Deposition Program (NADP) sites within and adjacent to the region. Model performance, which was tested against independent measurements from three physiographic regions of the eastern U.S.A., revealed a statistically significant reduction in interpolation error compared to traditional two-dimensional surface algorithms.

Air Pollutants↗
PubMed2004

Numerical simulation of the mechanics of a yeast cell under high hydrostatic pressure.

The mechanical effects of the compression of a yeast cell (Saccharomyces cerevisiae) under high hydrostatic pressure used for the processing of food and food ingredients are modelled and simulated with the finite-element method. The cell model consists of a cell wall, cytoplasm a lipid filled vacuole and the nucleus. Material parameters have been taken from literature or have been derived from thermodynamic relationships of water and lipids under high hydrostatic pressure. The model has been validated for a pressure load up to 250 MPa. Comparison of the volume reduction to in situ experimental observations reveals very good agreement. Dimensional analysis of the governing equations shows that transient pressure application in a high-pressure food process does not enhance structural inactivation (mechanical damage), unless pressure oscillation frequencies of 700 MHz are applied. The deformation of the cell under pressure deviates strongly from isotropic volume reduction. Especially, organelle membranes exhibit large effective strain values. Hydrostatic stress conditions are preserved in the interior part of the cell. A pressure load of 400 MPa, which is critical upon disruption of cell organelle membranes, generates an effective strain up to 80%. In the cell wall, the stress state is heterogeneous. Von-Mises stress reaches the critical value upon failure of the cell wall of 70+/-4 MPa at a pressure load between 415 and 460 MPa.

Biomechanical Phenomena↗
PubMed2006

Tissue Doppler assessment of longitudinal right and left ventricular strain and strain rate in pulmonary artery hypertension.

Tissue Doppler imaging (TDI) in 38 adult patients with pulmonary artery hypertension of varied etiology and normal left ventricular systolic function by two-dimensional transthoracic echocardiography showed significantly reduced peak systolic strain (SS) in all three segments of left ventricular free wall and ventricular septum and two of three segments of right ventricular free wall when compared to 29 adults with no clinical or echocardiographic evidence of heart disease and normal left and right ventricular systolic function. A similar reduction in peak diastolic strain (DS) was also noted in all three segments of left ventricular free wall and ventricular septum and one of three segments of right ventricular free wall. This reduction in strain indices in patients with pulmonary hypertension was noted irrespective of whether right ventricular systolic function was normal or reduced as assessed by two-dimensional transthoracic echocardiography. SS and DS rates also showed reductions in patients with pulmonary artery hypertension. Our study shows the potential value of TDI indices in identifying reduced regional left ventricular systolic and diastolic longitudinal function in patients with pulmonary artery hypertension and normal left ventricular systolic function by two-dimensional transthoracic echocardiography. This reduction in left ventricular function was noted in patients with both normal and reduced right ventricular systolic functions by two-dimensional echocardiography.

Adult↗
PubMed2001

Breast stroma plays a dominant regulatory role in breast epithelial growth and differentiation: implications for tumor development and progression.

Although growth factors and extracellular matrix (ECM) are recognized as important contributors to breast epithelial growth, morphogenesis, hormone responsiveness, and neoplastic progression, the influence of functional interactions between breast stromal and epithelial cells on these processes has not been defined. Using a novel three-dimensional cell-cell interaction model, we have compared the abilities of different mesenchymal cell types, including breast fibroblasts derived from reduction mammoplasty and tumor tissues, and human umbilical endothelial cells (HUVECs) to induce three-dimensional morphogenesis and growth of normal MCF10A and preneoplastic MCF10AT1-EIII8 (referred as EIII8) human breast epithelial cells. Our data demonstrate a requirement for organspecific fibroblasts in the induction of epithelial morphogenesis. Whereas inclusion of normal reduction mammoplasty fibroblasts inhibit or retard morphological conversion and growth of MCF10A and EIII8 cells, respectively, tumor-derived breast fibroblasts evoke ductal-alveolar morphogenesis of both MCF10A and EIII8 cells. The growth and morphogenesis inhibitory effects of normal fibroblasts remain even in the presence of estrogen because they are able to suppress the estrogen-induced growth of EIII8 cells, whereas tumor fibroblasts support and maintain estrogen responsiveness of EIII8 cells. The inductive morphogenic effects of tumor fibroblasts on EIII8 cells is further augmented by the inclusion of HUVECs because these cocultures undergo a dramatic increase in proliferation and branching ductal-alveolar morphogenesis that is accompanied by an increase in invasion, degradation of coincident ECM, and expression of MMP-9. Therefore, tumor fibroblasts confer morphogenic and mitogenic induction of epithelial cells, and further enhancement of growth and progression requires active angiogenesis. These data illustrate the importance of structural and functional interactions between breast stromal and epithelial cells in the regulation of breast epithelial growth and progression.

Breast↗
PubMed1986

An internal fixator for posterior application to short segments of the thoracic, lumbar, or lumbosacral spine. Design and testing.

A new spinal implant has been designed and biomechanical testing completed, intended for application to "short-segment" spinal defects such as disc degeneration, fracture, spondylolisthesis, or tumor. Major improvements over currently available devices include: only 2-3 vertebrae are spanned, not 5-7 as with Harrington rods; true three-dimensional fixation is achieved, preventing such problems as hook or rod dislocation; three-dimensional adjustment is easily accomplished, allowing fracture or spondylolisthesis reduction to be readily performed; attachment to vertebrae is by means of transpedicular screws eliminating deliberate encroachment into the spinal canal, such as Luque wires or Harrington hooks; no special alignment between screws is needed (such as with holes or slots in a plate), allowing screw placement to fully conform to anatomic structures; and laminectomy sites and lumbosacral junction are readily instrumented. Background investigations presented here for design of this device include: CT-defined pedicle morphometry showing that screws may be larger than those currently used; effect of pitch, minor diameter, and tooth profile on screw pull-out strength; mechanical testing of a compact, three-dimensionally adjustable, strong, nonloosening articulating clamp; and establishing of the relationship between depth of penetration and strength of fixation of transpeduncular screws.

Adolescent↗
PubMed1999

Three-dimensional measurement of cerebral microvascular plasma perfusion, glial fibrillary acidic protein and microtubule associated protein-2 immunoreactivity after embolic stroke in rats: a double fluorescent labeled laser-scanning confocal microscopic study.

Early astroglial response to post-ischemic microvascular hypoperfusion may contribute to progressive cerebral microcirculatory impairment and ischemic neuronal injury. Using laser-scanning confocal microscopy and three fluorescent probes, we measured in three-dimensions cerebral microvascular plasma perfusion, astrocytic reactivity, and neuronal injury assessed by fluorescein isothiocyanate (FITC)-dextran, GFAP immunoreactivity, and microtubule associated protein-2 (MAP2) immunoreactivity, respectively, in rats subjected to 2 h of middle cerebral artery occlusion. Three-dimensional quantitative analysis revealed that 2 h of embolic ischemia resulted in a significant (P<0.05) reduction of cerebral microvascular plasma perfusion in the ipsilateral cortex and subcortex. Tissue within the ipsilateral cortex and subcortex with low plasma perfusion exhibited a significant (P<0.05) increase in GFAP immunoreactivity compared with the homologous contralateral tissue. Three-dimensional re-constructed images showed that prominent GFAP immunoreactive astrocytes surrounded large vessels with decreased plasma perfusion in downstream capillaries in the ipsilateral MCA territory when compared to the vessels in the contralateral homologous tissue. Triple fluorescence probe-stained sections showed that tissue with decreased plasma perfusion and with increased GFAP immunoreactivity was accompanied by a reduction of MAP2 immunoreactivity. The present study demonstrates that an impairment of microvascular perfusion induces an early increase in GFAP immunoreactivity, and reactive astrocytes may contribute to a further reduction of cerebral microvascular plasma perfusion. The three-dimensional quantitative imaging analysis used in the present study provides a means to investigate parenchymal cellular responses to changes of cerebral microvascular plasma perfusion after MCA occlusion.

Animals↗
PubMed2000

Dimension reduction for highdimensional online-monitoring data in intensive care.

Nowadays high dimensional data in intensive care medicine can be captured, stored, and retrieved with the help of clinical information systems. Intelligent alarm systems are needed for an adequate bedside decision support, in the course of which the detection of qualitative patterns in physiologic monitoring data such as outliers, level changes, or trends aims at a proper classification of the patients state. Statistical time series techniques have already been applied successfully to the analysis of single physiological variables. The simultaneous online analysis of the multivariate patient curve yields further challenges. We describe methods for reducing the dimension and for keeping the computational efforts necessary for monitoring low. We present preliminary results of an ongoing study on monitoring critically ill patients.

Adult↗
PubMed1992

Cardioprotective effects of carvedilol, a novel beta adrenoceptor antagonist with vasodilating properties, in anaesthetised minipigs: comparison with propranolol.

OBJECTIVE: The aim was to evaluate in a minipig model of acute myocardial infarction the cardioprotection provided by the beta adrenoceptor blocking and vasodilating activities present in carvedilol; comparison was made to the pure beta adrenoceptor antagonist, propranolol. METHODS: Experiments were performed in 25 Yucatan minipigs (9-12 kg), randomly assigned to receive vehicle (n = 7), carvedilol 0.3 mg.kg-1 (n = 6), carvedilol 1 mg.kg-1 (n = 6), or propranolol 1 mg.kg-1 (n = 6). Myocardial infarction was produced by occlusion of the left anterior descending coronary artery for 45 min followed by 4 h of reperfusion. Vehicle, carvedilol (0.3 and 1 mg.kg-1) or propranolol (1 mg.kg-1) were given intravenously 15 min before the coronary artery occlusion. At the end of the reperfusion period, infarct size was determined using Evans blue dye and triphenyltetrazolium chloride staining. Infarct volumes were visualised using computer assisted three dimensional image analysis of the stained myocardial tissue sections. Myeloperoxidase activity was measured in tissue samples removed from normal, infarcted, and at risk areas. RESULTS: Carvedilol (1 mg.kg-1) reduced infarct size by over 90% without producing pronounced changes in systemic haemodynamic variables. The ability of carvedilol to reduce infarct size was clearly dose dependent. Thus infarct size, which represented 27.5(SEM 2.3)% of the area at risk in the vehicle treated group, was only 13.1(4.0)% (p < 0.05) and 2.4(1.5)% (p < 0.01) in pigs treated with carvedilol at 0.3 and 1 mg.kg-1, respectively. In animals treated with propranolol (1 mg.kg-1), infarct size represented 10.9(2.4)% of the area at risk (p < 0.05). The 60% and 91% reductions in infarct size produced by propranolol (1 mg.kg-1) and carvedilol (1 mg.kg-1), respectively, were clearly evident upon three dimensional image analysis. The reduction in infarct size was significantly greater for carvedilol (1 mg.kg-1) compared to propranolol (1 mg.kg-1) at equivalent beta adrenoceptor blocking doses. Pretreatment with propranolol did not reduce the increases in myeloperoxidase activity observed in the area at risk or in the infarcted area. In contrast, carvedilol produced a dose dependent reduction in myeloperoxidase activity in these areas. CONCLUSIONS: Carvedilol limits myocardial necrosis resulting from coronary artery occlusion and reperfusion in a more pronounced manner than the pure beta adrenoceptor antagonist, propranolol. The cardioprotective effect of carvedilol, which reduced infarct size by 91%, may result from the combined effects of beta adrenoceptor blockade and vasodilatation, and possibly also from inhibition of intracellular calcium overload in cardiac cells resulting from antagonism of myocardial alpha 1 adrenoceptors and/or calcium channel blockade. The cardioprotection provided by carvedilol may ultimately be of benefit in hypertensive patients who are at risk for acute myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed1998

Evaluation of two dose-volume histogram reduction models for the prediction of radiation pneumonitis.

PURPOSE: To evaluate the similarities between the mean lung dose and two dose-volume histogram (DVH) reduction techniques of 3D dose distributions of the lung. PATIENTS AND METHODS: DVHs of the lungs were calculated from 3D dose distributions of patients treated for malignant lymphoma (44), breast cancer (42) and lung cancer (20). With a DVH reduction technique, a DVH is summarized by the equivalent uniform dose (EUD), a quantity which is directly related to the normal tissue complication probability (NTCP). Two DVH reduction techniques were used. The first was based on an empirical model proposed by Kutcher et al. (Kutcher, G.J., Burman, C., Brewster, M.S., Goitein, M. and Mohan, R. Histogram reduction method for calculating complication probabilities for three-dimensional treatment planning evaluations. Int. J. Radiat. Oncol. Biol. Phys. 21: 137-146, 1991), which needs a volume exponent n. Several values for n were tested. The second technique was based on a radiobiological model, the parallel functional subunit model developed by Niemierko et al. (Niemierko, A. and Goitein, M. Modeling of normal tissue response to radiation: the critical volume model. Int. J. Radiat. Oncol. Biol. Phys. 25: 135-145, 1993) and Jackson et al. (Jackson, A., Kutcher, G.J. and Yorke, E.D. Probability of radiation-induced complications for normal tissues with parallel architecture subject to non-uniform irradiation. Med. Phys. 20: 613-625, 1993), for which a local dose-effect relation needed to be specified. This relation was obtained from an analysis of perfusion and ventilation SPECT data. RESULTS: It can be shown analytically that the two DVH reduction techniques are identical, if the local dose-effect relation obeys a power-law relationship in the clinical dose range. Local dose-effect relations based on perfusion and ventilation SPECT data can indeed be fitted with a power-law relationship in the range 0-80 Gy, from which values of n = 0.8-0.9 were deduced. These correspond to the commonly used value of n = 0.87 for lung tissue and yielded EUDn=0.87 values which were almost identical to the mean lung doses. For other n values, for which no experimental data are present, differences exist between EUD and mean dose values. Six patients with malignant lymphoma (6/44) and none of the breast cancer patients (0/42) developed radiation pneumonitis. These cases occurred only at high values for the mean lung dose. CONCLUSION: The two DVH reduction techniques are identical for lung and are very similar to mean dose calculations. The two techniques are also relatively similar for other model parameter values.

Breast Neoplasms↗
PubMed1997

In vitro amphotericin B effects on growth, viability and dimorphism of Paracoccidioides brasiliensis: reversal of the treatment.

The in vitro effects of amphotericin B deoxycholate suspension (fungizone) on Paracoccidioides brasiliensis growth, cell viability and transformation were investigated. We also analyzed the protein synthesis patterns of both cellular forms, yeast and mycelium in the presence of AmB. This drug, at 30 micrograms/ml, highly inhibited yeast growth, which could be recovered depending on treatment time, where the most effective reversion was observed after 6 hr of incubation. The yeast cell viability, that had been partially affected by the drug, could also be efficiently recovered after AmB was removed. The effect of AmB on the cellular dimorphism process showed a strong reduction in the mycelium to yeast transformation (80% inhibition compared to the control without the drug). On the other hand, the transformation from yeast to mycelium in the presence of AmB was 50% affected, relative to the control. In contrast to the growth and cell viability experiments, the reversion effects on dimorphism were partial when the drug was removed, even with only 6 hr treatment. The two-dimensional gels of 35S-labeled proteins revealed a strong reduction in the three species of 80, 71 and 56 kDa in yeast and mycelium when treated with AmB.

Amphotericin B↗
PubMed2006

Stable knockdown of polycystin-1 confers integrin-alpha2beta1-mediated anoikis resistance.

The mechanisms of action of polycystin-1 (PC1) have been difficult to dissect because of its interaction with multiple factors, the heterogeneity of the genetic mutations, and the complexity of the experimental animal models. Here, stable knockdown of PC1 in MDCK epithelial cells was achieved by lentiviral-mediated delivery of a specific small interfering RNA for PKD1. The reduction of PC1 expression prevented tubulogenesis in three-dimensional collagen type I culture in response to hepatocyte growth factor and induced formation of cysts. PC1 knockdown created a condition of haploinsufficiency that led to hyperproliferation, increased adhesion to collagen type I, and increased apoptosis. It was shown that the suppression of PC1 was associated with the increased expression of integrin-alpha2beta1 and reduced apoptosis in cells grown on collagen type I. The engagement of integrin-alpha2beta1 seemed to be essential for the survival because PC1 knockdown cells were significantly less susceptible to anoikis by a mechanism that was reversible by anti-integrin-alpha2beta1 blocking antibodies. Overall, these data link integrin-alpha2beta1 to some of the biologic functions that are ascribed to PC1 and establish the potential of this approach for the direct study of PC1 functions in a genetically defined background. Furthermore, these findings indicate that reduction of PC1 expression levels, rather than the loss of heterozygosity, may be sufficient to induce cystogenesis.

Animals↗
PubMed2005

A note on the asymptotic reduction of the Hodgkin-Huxley equations for nerve impulses.

The (standard) FitzHugh reduction of the Hodgkin-Huxley equations for the propagation of nerve impulses ignores the dynamics of the activation gates. This assumption is invalid and leads to an over-estimation of the wave speed by a factor of 5 and the wrong dependence of wave speed on sodium channel conductance. The error occurs because a non-dimensional parameter, which is assumed to be small in the FitzHugh reduction, is in fact large (approximately 18). We analyse the Hodgkin-Huxley equations for propagating nerve impulses in the limit that this non-dimensional parameter is large, and show that the analytical results are consistent with numerical simulations of the Hodgkin-Huxley equations.

Action Potentials↗
PubMed1991

Chemical exchange in two dimensions in the 1H NMR assignment of cytochrome c.

The important role played by chemical exchange in solving the proton assignment problem for oxidized and reduced horse cytochrome c is described. Some novel approaches for establishing oxidation-reduction exchange correlations in combinations of several two-dimensional spectra were used. Unambiguous chemical exchange correlations were established for 55 NH-C alpha H resonances and all the aromatic and side chain methyl resonances. Consistent although not fully unambiguous main chain proton correlations were observed for 47 of the remaining 49 residues. The many exchange correlations found serve to multiply cross-connect the two extensive, individually self-consistent networks of assignments found for the oxidized and reduced forms, and thus help to confirm both sets of assignments.

Cytochrome c Group↗
PubMed2003

Hilbert series, Howe duality, and branching rules.

Let lambda be a partition, with l parts, and let F(lambda) be the irreducible finite dimensional representation of GL(m) associated to lambda when l < or = m. The Littlewood Restriction Rule describes how F(lambda) decomposes when restricted to the orthogonal group O(m) or to the symplectic group Sp(m2) under the condition that l < or = m2. In this paper, this result is extended to all partitions lambda. Our method combines resolutions of unitary highest weight modules by generalized Verma modules with reciprocity laws from the theory of dual pairs in classical invariant theory. Corollaries include determination of the Gelfand-Kirillov dimension of any unitary highest weight representation occurring in a dual pair setting, and the determination of their Hilbert series (as a graded module for p(-)). Let L be a unitary highest weight representation of sp(n, R), so*(2n), or u(p, q). When the highest weight of L plus rho satisfies a partial dominance condition called quasi-dominance, we associate to L a reductive Lie algebra g(L) and a graded finite dimensional representation B(L) of g(L). The representation B(L) will have a Hilbert series P(q) that is a polynomial in q with positive integer coefficients. Let delta(L) = delta be the Gelfand-Kirillov dimension of L and set c(L) equal to the ratio of the dimensions of the zeroth levels in the gradings of L and B(L). Then the Hilbert series of L may be expressed in the form H(L)(q)=c(L) P(q)(1-q)(delta). In the easiest example of the correspondence L --> B(L), the two components of the Weil representation of the symplectic group correspond to the two spin representations of an orthogonal group.

Journal Article↗
PubMedDate not supplied

Studies on thymic epithelial cells in vitro.

Thymic epithelial cells are unique in their ability to support positive selection and are essential throughout thymocyte development. Here, we describe a technique for measuring the proliferation of thymic epithelial cells by flow cytometry using a combination of BrdU and pancytokeratin labelling, and we examine the effects of different in vitro culture strategies on thymic epithelial cell function. We find that at d15 gestation, 74% (+/- 0.4%) of thymic epithelial cells are in cycle, which declines to 63% (+/- 1.3%) by d16, and to 34% (+/- 1.9%) by d18. This decline in proliferation is also found in organ cultures and in cultures depleted of lymphoid cells by 2-dGuo, suggesting that the cell cycle status of thymic epithelial cells is independent of the lymphoid population. When cultured in vitro as 3-dimensional aggregates, purified MHC class II+ thymic epithelial cells retain the ability to support thymocyte maturation. In contrast, 2-dimensional monolayer culture abrogates the ability of these cells to support positive selection, causes a reduction in whn gene expression and reduces their ability to re-form coherent reaggregate structures. Intact lobes and 3-dimensional aggregates are therefore the best way of maintaining thymic epithelial cell function and gene expression in vitro.

Animals↗
PubMed2006

Functional holography analysis: simplifying the complexity of dynamical networks.

We present a novel functional holography (FH) analysis devised to study the dynamics of task-performing dynamical networks. The latter term refers to networks composed of dynamical systems or elements, like gene networks or neural networks. The new approach is based on the realization that task-performing networks follow some underlying principles that are reflected in their activity. Therefore, the analysis is designed to decipher the existence of simple causal motives that are expected to be embedded in the observed complex activity of the networks under study. First we evaluate the matrix of similarities (correlations) between the activities of the network's components. We then perform collective normalization of the similarities (or affinity transformation) to construct a matrix of functional correlations. Using dimension reduction algorithms on the affinity matrix, the matrix is projected onto a principal three-dimensional space of the leading eigenvectors computed by the algorithm. To retrieve back information that is lost in the dimension reduction, we connect the nodes by colored lines that represent the level of the similarities to construct a holographic network in the principal space. Next we calculate the activity propagation in the network (temporal ordering) using different methods like temporal center of mass and cross correlations. The causal information is superimposed on the holographic network by coloring the nodes locations according to the temporal ordering of their activities. First, we illustrate the analysis for simple, artificially constructed examples. Then we demonstrate that by applying the FH analysis to modeled and real neural networks as well as recorded brain activity, hidden causal manifolds with simple yet characteristic geometrical and topological features are deciphered in the complex activity. The term "functional holography" is used to indicate that the goal of the analysis is to extract the maximum amount of functional information about the dynamical network as a whole unit.

Algorithms↗
PubMed1989

Development of Y-axon innervation of cortical area 18 in the cat.

1. Geniculocortical Y-axons (n = 38) in the optic radiations of 4-5-week-old kittens (n = 20) and adult cats (n = 18) were studied both physiologically and morphologically. Axons were recorded from intracellularly and subsequently filled ionophoretically with horseradish peroxidase (HRP). The HRP filled the axons' terminal arborizations in visual cortex (particularly well for those innervating area 18). Fourteen axons appeared to be completely filled with HRP (n = 8 in kitten, n = 6 in adult) and served as the basis for the quantitative analysis of the terminal arborizations reported in this study. 2. The distribution and correspondence of the axonal boutons to presynaptic elements in cortical layer 4A was analysed at both the light and electron microscope level using computerized three-dimensional analysis and serial section reconstruction, respectively. Compared to adult axons, the boutons of the kitten axons were smaller (means = 0.75 vs. 1.75 microns length, P less than 0.001) and more densely spaced both along individual axon branches (means = 6.60 vs. 11.20 microns interbouton interval, P less than 0.001) and between neighbouring branches of the same axon (means = 4.7 vs. 6.4 microns nearest-neighbour distance, P less than 0.01). 3. Most kitten boutons made a single Gray's type 1 synapse on a cortical neurone, unlike adult boutons which usually contacted two or more postsynaptic targets. Both kitten and adult axons had dendritic spines as their major target. Occasionally, HRP reaction-product was observed in cortical neurones postsynaptic to the labelled geniculocortical axon, which gave some estimate of the number of synaptic contacts between a single geniculocortical axon and target cell (about five). 4. The kitten Y-axons innervated the visual cortex in a pattern similar to that of the adult, with the richest terminal branching and bouton density in layer 4A with some additional boutons distributed in layers 3, 4B and 6. The extent of the terminal arborizations primarily in layer 4A (as measured in surface views) of kitten Y-axons in area 18 was significantly less than that of adult Y-axons in area 18 (means = 0.9 mm2 vs. means = 1.2 mm2, P = 0.04). 5. We conclude that between 4 and 5 postnatal weeks and 1 year, geniculocortical Y-axons projecting to cortical area 18 undergo four major changes. These include a reduction in synaptic bouton density (both in three-dimensional space and along individual branches), a concomitant moderate expansion in the surface area of cortex innervated, an increase in bouton size and an increase in the number of synaptic contacts made by each bouton. A general proportional growth of the individual axons' terminal arborization together with fusion and/or separation of neighbouring boutons is sufficient to explain this development.

Aging↗