Biomedical subjects

H Kennedy

Publications and source records attributed to H Kennedy.

At least 37 records · Page 2Linked to original sources

PubMed1998

Area-specific laminar distribution of cortical feedback neurons projecting to cat area 17: quantitative analysis in the adult and during ontogeny.

Corticocortical pathways can be classified as feedback and feedforward, in part according to the laminar distribution of the parent cell bodies. Here, we have developed exhaustive sampling procedures to determine unambiguously this laminar distribution. This shows that individual extrastriate areas in the adult cat have highly stereotyped proportions of supragranular layer neurons with respect to the total population of neurons back-projecting to area 17. During development, these adult laminar patterns emerge from an initially uniform radial distribution through a process of selective reorganization, which is highly specific to each area. Injections of fluorescent retrograde tracers were made in area 17. In areas 19, 20, posteromedial lateral suprasylvian area, and anteromedial lateral suprasylvian area, we defined a projection zone as the region containing retrogradely labeled neurons. In the neonate, counts of labeled neurons throughout the projection zones show constant percentages of 40% in the supragranular layers. During development, there is an area-specific reduction in the percentage of supragranular labeled neurons generating the laminar distributions characteristic of each area. Numbers of labeled neurons were estimated at different eccentricities of the projection zone. This finding indicates that during development there is a relative decrease in the numbers of labeled neurons of the periphery of the projection zone in the supragranular layers but not in the infragranular layers. This decrease is accompanied by a relative decrease in the dimensions of the supragranular projection zone with respect to the infragranular projection zone. These findings suggest that each extrastriate area precisely adjusts the proportions of supragranular layer neurons back-projecting to striate cortex in part by developmental changes in the divergence-convergence values of individual neurons. This shaping of corticocortical connectivity occurs relatively late in postnatal development and could, therefore, be under epigenetic control.

Animals↗

PubMed1998

Splanchnic retention of intraduodenal and intrajejunal glucose in healthy adults.

Estimates of the spanchnic retention and appearance in the systemic circulation of orally administered glucose vary among laboratories even after recently identified sources of error have been accounted for [Livesey, G., P. D. G. Wilson, J. R. Dainty, J. C. Brown, R. M. Faulks, M. A. Roe, T. A. Newman, J. Eagles, F. A. Mellon, and R. Greenwood. Am. J. Physiol. 275 (Endocrinol. Metab. 38): E717-E728, 1998]. We questioned whether, in healthy humans, D-glucose delivered intraluminally to the midjejunum appeared systemically as extensively as that delivered intraduodenally. Subjects were infused over a period of 90 min with 50 g of glucose in 1 liter of isotonic saline (incorporating 0.5 g D-[13C6]glucose) per 70 kg of body weight. Infusions were via enteral tubes terminating approximately 15 and 100 cm postpylorus. The systemic appearance of glucose was monitored by means of a primed-continuous intravenous infusion of D-[6,6-2H2]glucose. Whereas 98 +/- 2% (n = 7) of the duodenally infused glucose appeared in the systemic circulation, only 35 +/- 9% (n = 7) of midjejunally infused glucose did so, implying that 65 +/- 9% was retained in the splanchnic bed. Either glucose was less efficiently absorbed at the midintestinal site or hepatic glucose sequestration was increased 10-fold, or both. The proximal intestine plays a key role in the delivery of glucose to the systemic circulation, and the distal intestine potentially delivers more glucose to the liver.

Adult↗

PubMed1997

Regulation of neuroblast cell-cycle kinetics plays a crucial role in the generation of unique features of neocortical areas.

Cortical neurons are generated in the germinal zones lining the ventricles before migrating predominantly radially. To investigate regional differences in the cell-cycle kinetics of neuroblasts, pulse [3H]-thymidine injections were made throughout corticogenesis, and labeled neuron counts were compared in areas 3, 6, 17, and 18a in the adult mouse. The relationship between height in the cortex and intensity of autoradiographic signal distinguishes first generation and subsequent generations of neurons. This provides the mitotic history of defined sets of neurons and is a powerful tool for analyzing areal differences in cell-cycle kinetics. The infragranular laminar labeling indices of different generations show significant differences in areas 3 and 6. The labeling index of first generation neurons shows that the rate of neuron production is higher in area 3 than in area 6. This increased generation rate in area 3 was accompanied by two major changes. First, computation of the labeling index of the subsequent generation neurons (which reflects percentages of precursors in S-phase at the moment of the pulse) indicates a shorter cell cycle in area 3. Second, the total population of labeled neurons contains a higher proportion of first generation neurons in area 3, implying a higher leaving fraction in this area. Computer simulations of these areal differences of cell-cycle kinetics generate neuron numbers that are in close agreement with published data. Altogether these findings reveal an early regionalization of the ventricular zone that serves to generate unique features of future cortical areas.

Aging↗

PubMed1997

The timetable of laminar neurogenesis contributes to the specification of cortical areas in mouse isocortex.

In the primate visual cortex, the birthdate of neurons in homologous layers differ on either side of the 17-18 border suggesting that there might be different timetables of laminar histogenesis in these two areas (Dehay et al. [1993] Nature 366:464-466 and Kennedy et al. [1996] Soc. Neurosci. Abst. 22:525). Because of the potential importance of these findings for understanding mechanisms that generate areal identity, we have developed an experimental approach that makes it possible to accurately compute the timetable of laminar histogenesis from birthdating experiments. Here we report the results of an exhaustive examination of the tempo of layer production in five cortical areas of the mouse. Tritiated thymidine pulse injections were made during embryonic development and labeled neurons were examined in three frontoparietal areas (areas 3, 4, and 6) and two occipital areas (areas 17 and 18a) of the adult cortex. The correlation between the radial distribution of neurons and the intensities of labeling enabled us to reliably identify first generation neurons (i.e., those neurons that quit the cell-cycle in the first round of mitosis after injection). For each cortical layer, the percentage of first generation neurons with respect to the total number of neurons defined a laminar labeling index. Changes of the laminar labeling index over time determined the timetable of layer formation. The onset and duration of layer formation was identical in the two occipital areas. This finding contrasted with the frontoparietal areas where there were important differences in the timing of infragranular and granular layer formation and noticeably production of layers VIa, V, and IV occurs earlier in area 3 than in area 6. The timing of laminar production of areas 17 and 18a resembles more that of area 3 than that of area 6. With respect to areas 3 and 6, area 4 shows an intermediate but significantly different timetable of layer production. These marked areal differences in the timetable of laminar histogenesis contrasted with the relative homogeneity within areas so that we have been able to demonstrate that the interareal differences are not merely the expression of known neurogenic gradients. These results suggest that in the mouse frontoparietal isocortex, neighbouring regions of the ventricular zone that will give rise to distinct areas follow distinct programs of layer production. These areal differences occur before thalamic innervation and suggest an early regionalisation of laminar histogenesis.

Animals↗

PubMed1996

Phenotypic characterisation of respecified visual cortex subsequent to prenatal enucleation in the monkey: development of acetylcholinesterase and cytochrome oxidase patterns.

Prenatal bilateral enucleation induces cortex, which normally would have become striate cortex, to follow a default developmental pathway and to take on the cytoarchitectonic appearance of extrastriate cortex (default extrastriate cortex, Dehay et al. [1996] J. Comp. Neurol. 367:70-89). We have investigated if this manipulation influences the cortical expression of acetylcholinesterase (AChE) and cytochrome oxidase (CO). Early enucleation (before embryonic day 81; E81) had only minor effects on the distribution of AChE and CO in the striate cortex. In animals that underwent operation, the striate cortex CO blobs were significantly more closely spaced on the operculum compared with the calcarine. After early enucleation, there was a periodic distribution of CO dense patches in default extrastriate cortex. These CO patches had a center-to-center spacing that was considerably smaller than that of CO stripes in normal area V2, but was somewhat larger than that of the CO blobs in striate cortex. Although the CO stripes characteristic of normal area V2 could not be detected, there were some high-frequency CO patches, similar to those found in default extrastriate cortex. Early enucleation caused a failure to form the transient AChE bands running perpendicular to the striate border, which are normally present in the fetus and early neonate. Late enucleation did not alter AChE expression in extrastriate cortex. The relatively minor effects of early enucleation in the reduced striate cortex contrast with the changes in expression of these enzymes in extrastriate cortex, which accompany large shifts in the location of the striate border. This suggests a massive reorganisation of cortical phenotype in extrastriate cortex.

Acetylcholinesterase↗

PubMed1996

Role of directed growth and target selection in the formation of cortical pathways: prenatal development of the projection of area V2 to area V4 in the monkey.

In experiments combining retrograde tracers and histochemistry, we have looked at the prenatal development of the cortical pathway linking areas V2 and V4. Transient expression of acetylcholinesterase in fetal area V2 reveals the separate compartments that project to V4 (temporal directed pathway) and V5 (parietal directed pathway). During early stages of pathway formation, V2 neurons projecting to area V4 are clustered in the appropriate compartments. During the phase of rapid axonal growth, there is a selective increase of connections originating from the appropriate compartments leading to a strongly clustered organization at the peak of connectivity. During this phase, injections involving the white matter also showed clustering, but this was somewhat reduced in comparison to that of gray matter injections. The growth phase is followed by an elimination phase during which there is a tendency for a preferential loss of intercluster connections, which may sharpen the early formed pattern. These results demonstrate the primary role of axonal guidance and target recognition mechanisms followed by a limited extent of selective elimination during the formation of functional cortical pathways in the primate isocortex. Compared to previous findings, these results suggest that the developmental restriction of callosal connections is not a universal model of cortical development. In the present report, the directed growth and early specification of feed-forward connections contrast with the prolonged remodelling of monkey feedback projections, suggesting two distinct developmental strategies of pathway formation in the monkey.

Acetylcholinesterase↗

PubMed1996

Contribution of thalamic input to the specification of cytoarchitectonic cortical fields in the primate: effects of bilateral enucleation in the fetal monkey on the boundaries, dimensions, and gyrification of striate and extrastriate cortex.

Bilateral enucleation was performed at different fetal ages during corticogenesis, and the brains were prepared for histological examination. Early-enucleated fetuses (operated prior to embryonic day 77) showed morphological changes at the level of the thalamus and the cortex. In the thalamus, there was a loss of lamination and a decrease in size of the lateral geniculate nucleus. There was a decrease in the size of the inferior pulvinar, but there was no change in the lateral pulvinar. The border of striate cortex was as sharp in the enucleates as it was in the normal monkeys. In three of the four early enucleates, we observed an interdigitation of striate and extrastriate cortex. In three of the early enucleates, we observed a small island of nonstriate cortex near the striate border that was surrounded entirely by striate cortex. Enucleation led to an age-related reduction of striate cortex. This reduction was greater in the operculum than in the calcarine fissure. The reduction of striate cortex was accompanied by an increase in the dimensions of extrastriate visual cortex, so that the overall dimensions of the neocortex remained invariant. The extrastriate cortex in the enucleated animals presented a uniform cytoarchitecture and was indistinguishable from area 18 in the normal animal. There were changes in the gyral pattern that were restricted mainly to the cortex on the operculum. A deepening of minor dimples as well as the induction of a variable number of supplementary sulci led to an increase in the convolution of the occipital lobe. These results are discussed with respect to the specification of cortical areas. They demonstrate that the reduction in striate cortex was not accompanied by an equivalent reduction in the neocortex; rather, there was a border shift, and a large volume of cortex that was destined to become striate cortex appears to be cytoarchitectonically normal extrastriate cortex.

Aging↗

PubMed1996

Aspergillosis in immunocompromised paediatric patients: associations with building hygiene, design, and indoor air.

BACKGROUND: Nosocomial aspergillosis is a well known complication of immunosuppression in cancer patients and those undergoing transplantation and has usually been associated with major building construction or demolition. An observational study is reported of the hospital environment associated with an outbreak of aspergillosis in a paediatric oncology ward. METHODS: All cases of aspergillosis were identified from the hospital records and categorised as definite or probable according to the extent of supportive clinical and laboratory findings. All relevant aspects of building ventilation, air filtration, and aerosol generation considered relevant were examined and air samples for fungi were taken in triplicate at 25 sites using a slit sampler with appropriate culture media. RESULTS: Six cases of aspergillosis were identified over one year out of the 148 patients who attended the unit - the only part of the hospital where cases were found. Examination of the building services and function suggested that the cause or source was isolated to this paediatric oncology/haematology ward and may have been attributed to a defective disposal conduit door as well as the dispersal of a contaminated aerosol from the ward vacuum cleaner which had the highest measured concentrations of Aspergillus fumigatus in or around the building (65 colony forming units (cfu)/m3 compared with 0-6 cfu/m3 elsewhere). No further cases were identified in the two years after these hygiene arrangements were changed. CONCLUSIONS: The investigation of this outbreak of nosocomial aspergillosis identified several possible sources of fungally contaminated aerosol which could have been implicated as the cause. Their modification was followed by a reduction in the incidence of further cases. Each should be incorporated as an issue of importance in hospital building design and hygiene.

Air Pollution, Indoor↗

PubMed1996

Evidence that Lp[a] contains one molecule of apo[a] and one molecule of apoB: evaluation of amino acid analysis data.

Amino acid analysis was performed on four Lp[a] preparations to evaluate whether or not the amino acid data was consistent with Lp[a] containing one molecule of apolipoprotein[a] [apo(a)] linked to one molecule of apoB-100. Amino acid analysis was carried out in duplicate on a Beckman model 121 amino acid analyzer. Apo[a] size was determined by a high-resolution agarose gel electrophoretic method that provides an estimate of apo[a] kringle 4 repeats. When Lp[a] was assumed to contain one apo[a] and one apoB molecule per particle, the average absolute bias between the expected molar percentage of each amino acid, as based on the known sequence of apo[a] and apoB, and the obtained molar percentage ranged from 2 to 3.5%. In contrast, by assuming two molecules of apo[a] and one of apoB per Lp[a] particle, the bias between the expected and observed molar percentage ranged from 8.5% to 10%, and by assuming one apo[a] and two apoB the bias ranged from 8.8% to 11.4%. Comparison of Lp[a] concentrations, calculated from six stable amino acids and the Lp[a] composition predicted from the known sequence, was in excellent agreement (bias ranging from 0.3% to 0.9%) with the Lp[a] concentration calculated from the sum of the amino acid concentrations, when Lp[a] was assumed to contain one molecule of apo[a] and one molecule of apoB. However, there was poor agreement (7.4% to 8.4% bias) when it was assumed that Lp[a] contains two molecules of apo[a] and one molecule of apoB. These results indicate that the evaluated Lp[a] preparations contain one apo[a] per Lp[a] particle. Evaluation of amino acid analysis data provides a relatively simple approach to determine the molar ratio of apoB to apo[a] in Lp[a] and provides evidence that Lp[a] contains one molecule of apo[a] and one molecule of apoB.

Amino Acids↗

PubMed1996

Differences in Lp[a] concentrations and apo[a] polymorphs between black and white Americans.

Lp[a] concentrations in nmol/L and apo[a] size isoforms, expressed in terms of the relative number of apo[a] kringle 4 (K4) repeats, were determined in 3959 whites and blacks from four U.S. communities. Plasma Lp[a] analyses were performed by an ELISA method insensitive to apo[a] size heterogeneity and apo[a] size isoforms were determined by high resolution agarose gel electrophoresis. Allele frequencies were estimated by maximum likelihood methods in order to account for the presence of null alleles and coalescence of hands on gels. The apo[a] allele frequencies and phenotype distributions differed significantly between blacks and whites (P < 0.0001). Blacks had a higher relative frequency of the intermediate alleles K4(22) through K4(28) whereas whites had a higher relative frequency of the small alleles K4(17) through K4(24) and large alleles K4(29) through K4(33). The estimated frequency of the null allele was low in both blacks (1.0%) and whites (6.7%). The Lp[a] distribution was less skewed and Lp[a] concentrations were higher in blacks than whites (mean 94 nmol/L and 48 nmol/L, median 74 nmol/L and 20 nmol/L for blacks and whites, respectively). The relationship between apo[a] size and Lp[a] concentration also differed significantly between these two racial groups. For the large polymorphs (> 31 K4 repeats) both blacks and whites exhibited uniformly low Lp[a] values. For the intermediate isoforms K4(20) through K4(30), a considerable range of Lp[a] values was evident in blacks; the median Lp[a] for each isoform increased nearly linearly as the apo[a] size decreased. In contrast in whites there was little change in median Lp[a] concentrations for isoforms K4(20) through K4(30). For the small apo[a] size (< 20 K4) both blacks and whites exhibited high median Lp[a] levels and a wide variation of Lp[a] levels. The major difference in Lp[a] levels between the two racial groups occurred in the intermediate size isoform range of K4(20) through K4(25). In conclusion, whites and blacks differ significantly in Lp[a] concentrations, allele and phenotype frequencies, and in the relationship between apo[a] size isoform and Lp[a] concentration.

Adolescent↗

PubMed1995

Nutritional screening--evaluation and implementation of a simple Nutrition Risk Score.

Development of a simple, validated Nutrition Risk Score for identification of patients at risk of undernutrition is described. The score is easy to use, applicable to all patient categories and ages, and correlated well with a validated Nutrition Risk Index (r = 0.68, p < 0.001) and clinical impression (r = 0.83, p < 0.001). Reproducible scores were obtained between dietitians (r = 0.91, p < 0.001) and between dietitians and nursing staff (r = 0.80, p < 0.001). The score was used to assess risk of undernutrition in 153 consecutive admissions to medical and surgical specialties. Patients were categorised as low (50%), moderate (24%) or high risk (26%). Evaluation of measures to prevent nutritional depletion revealed that no action was taken in 64% (23/36) of moderate risk and 30% (12/40) of high risk patients. Implementation of routine, hospital-wide nutritional screening, to identify patients in need of nutritional support, has been achieved by inclusion of the score in the standard nursing assessment process.

Journal Article↗

PubMed1995

Influence of the physical form of barley grain on the digestion of its starch in the human small intestine and implications for health.

It has been suggested that incomplete digestion of cereal starch explains the low energy values of certain cereals of large particle size. We used human subjects with ileostomies to investigate the digestion of barley and to determine whether the physical form of barley affects stomal excretion of starch, glucooligosaccharides, nitrogen, fat, and calculated energy. Only 2 +/- 1% of starch remained undigested after finely milled barley was eaten, but after flaked barley was eaten 17 +/- 1% resisted digestion, partly as oligosaccharides (G1-G10) but largely as intact unpitted starch granules bound by intact cell walls. The calculated energy excretion from the stoma was three times higher after flaked than after milled barley [51.5 decreasing to 15.3 kJ/g nonstarch polysaccharide (NSP, P < 0.001]. NSP, starch, and fat made almost equal contributions to the higher energy excretion. It is concluded that possibly the botanical source of cereals and certainly processing, other than retrogradation of the starch, are important determinants of starch digestibility and energy value. Possible clinical implications are introduced.

Adult↗

PubMed1995

Spatial reciprocity of connections between areas 17 and 18 in the cat.

We examined whether the interconnections between areas 17 and 18 are spatially reciprocal, i.e., whether a column of cells in area 17 receives from the same region of area 18 as it sends projections to, and vice versa. We addressed this question by making side by side injections of retrograde fluorescent tracers in area 18, calculating the convergence and divergence of the connections from area 17 to 18. We compared these values with previously reported values of divergence and convergence of the projections from area 18 to area 17. The results demonstrate that there is a good match between the convergence and divergence of the area 17 to area 18 connection and, respectively, the divergence and convergence of the reverse connection. We confirmed directly the spatial reciprocity by injecting simultaneously in area 17 a retrograde and an anterograde tracer and by analyzing quantitatively the density of anterograde and retrograde labeling across the surface of area 18. There was an excellent match between the density maps of retrogradely labeled cells and anterogradely labeled axon terminals in area 18. Connections between areas 17 and 18 therefore exhibit large degrees of convergence and divergence and are spatially reciprocal. Thus, a given column of cells within one of these two areas is reciprocally interconnected with a large region of the opposite area. Such an organization may provide the basis for synchronization of firing of neurons across these two areas, as revealed by cross-correlation studies.

Amidines↗

PubMed1995

Johann Baptist von Schweitzer: the queer Marx loved to hate.

Despite his conviction on a morals charge involving a boy, the early German Social Democrat Johann Baptist von Schweitzer went on to have a successful political career. His life furnishes the context to present remarks by his political opponents Marx and Engels, which reveal their deep-seated homophobia. It is pointed out that this has been glossed over by the translations of the recently published Marx/Engels Collected Works. Some remarks on boy-love and anarchism are appended.

Communism↗

PubMed1995

Levels of lipoprotein(a), apolipoprotein B, and lipoprotein cholesterol distribution in IDDM. Results from follow-up in the Diabetes Control and Complications Trial.

Levels of lipoprotein(a) [Lp(a)], apolipoprotein (apo) B, and lipoprotein cholesterol distribution using density-gradient ultracentrifugation were measured as part of a cross-sectional study at the final follow-up examination (mean 6.2 years) in the Diabetes Control and Complications Trial. Compared with the subjects in the conventionally treated group (n = 680), those subjects receiving intensive diabetes therapy (n = 667) had a lower level of Lp(a) (Caucasian subjects only, median 10.7 vs 12.5 mg/dl, respectively; P = 0.03), lower apo B (mean 83 vs. 86 mg/dl, respectively; P = 0.01), and a more favorable distribution of cholesterol in the lipoprotein fractions as measured by density-gradient ultracentrifugation with less cholesterol in the very-low-density lipoprotein and the dense low-density lipoprotein fractions and greater cholesterol content of the more buoyant low-density lipoprotein. Compared with a nondiabetic Caucasian control group (n = 2,158), Lp(a) levels were not different in the intensive treatment group (median 9.6 vs. 10.7 mg/dl, respectively; NS) and higher in the conventional treatment group (9.6 vs. 12.5 mg/dl, respectively; P < 0.01). No effect of renal dysfunction as measured by increasing albuminuria or reduced creatinine clearance on Lp(a) levels could be demonstrated in the diabetic subjects. Prospective follow-up of these subjects will determine whether these favorable lipoprotein differences in the intensive treatment group persist and whether they influence the onset of atherosclerosis in insulin-dependent diabetes.

Adolescent↗

PubMed1994

Topography of developing thalamic and cortical pathways in the visual system of the cat.

Adult patterns of connectivity could emerge during development by a process of selective elimination from an earlier, more widespread, connectivity. We have addressed this issue by examining the topography of developing projections to area 17 in the cat. At different postnatal ages, paired injections of the retrograde tracers diamidino yellow and fast blue were made in area 17. Interinjection separations were carefully controlled and the spatial distribution of the two populations of labelled neurones investigated. Projections to the striate cortex from the lateral geniculate nucleus, area 18, as well as connections intrinsic to area 17 were analysed quantitatively with a graphic method that uses a two-dimensional model of the projection. This allows two parameters of the projection to be calculated: the divergence (the spatial extent of area 17 contacted by an infinitely small region of an afferent structure) and the convergence (the extent of an afferent structure that projects to an infinitely small region of area 17). During postnatal development, the bulk of the connections making up the geniculostriate and corticocortical pathways showed no variation either in their convergence and divergence. However, the projection of area 18 to area 17 and the intrinsic area 17 connections (but not the geniculostriate projection) in the 3-15-day-old kittens were each found to contain a small subpopulation of widely scattered neurones with widespread axonal trajectories. These results, showing that many initially formed connections display a high degree of topographical order, are discussed in terms of the control mechanisms specifying axonal trajectories during development.

Aging↗

PubMed1994

cDNA cloning, expression and primary structure of Par jI, a major allergen of Parietaria judaica pollen.

A 659 bp cDNA clone** coding for an allergen of Pj pollen has been isolated from a lambda gt11 library, and its DNA sequence determined. The cDNA insert showed an open reading frame of 429 bp coding for an allergenic protein of 14,866 Da and a deduced amino acid sequence containing 143 residues. The expressed recombinant protein represented the major allergen Par jI since it reacted with 95% of the sera from Pj-allergic patients (n = 22) and with two Par jI-specific monoclonal antibodies. No similarity with other known DNA and protein sequences has been detected.

Allergens↗

PubMed1994

Developmental changes in the distribution of acetylcholinesterase in the extrastriate visual cortex of the monkey.

In the fetal and neonatal monkey, periodically organized regions of high activity of acetylcholinesterase were found in the visual cortical area V2 (Area 18). The acetylcholinesterase bands, like the thin and thick stripes of cytochrome oxidase, were found to run orthogonal to the area 17/18 border. During neonatal development these bands progressively narrow and finally disappear shortly after four months of age.

Acetylcholinesterase↗