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Biomedical subjects

A Peters

Publications and source records attributed to A Peters.

At least 19 recordsLinked to original sources

Symmetric synapses formed by callosal afferents in rat visual cortex.

Following an electron microscopic examination of 437 degenerating terminals of callosally projecting axons in layer II/III at the 17/18a border, it has been found that some of these terminals form symmetric synapses with dendritic shafts (1.83%), pyramidal cell bodies (1.37%) and dendritic spines (0.46%). The remainder of the axon terminals (96.33%) form asymmetric synapses, mainly with dendritic spines although a few form synapses with dendrites. These results suggest that in the rat visual cortex the corpus callosum is a source of both inhibitory and excitatory input to the contralateral hemisphere.

Afferent Pathways

Axon terminals on Betz cell somata of area 4 in rhesus monkey throughout adulthood.

Previous work in our laboratory demonstrated an age-related decline in the size of Betz cell somata in cortical area 4 of the adult rhesus monkey brain. The present study was conducted to determine whether changes might also occur in the axon terminals upon these cortical cells. Tissue from area 4 was collected from seven rhesus monkeys and prepared for electron microscopy. The ages of the monkeys ranged from 5 to 35 years, covering the entire adult life span of this species. A total of 140 Betz cell profiles (20 per monkey) were examined. Measurements of these profiles confirmed our earlier finding of a decline in the perimeters of Betz cell somata with advancing age. The 1,540 axon terminals upon these cells, however, remained unchanged in size and length of membrane apposition, as well as in their number of mitochondria throughout the adult life (greater than or equal to 5 years) of the rhesus monkey. In addition, the total number of axon terminals on Betz cells did not change with age. Because the axosomatic terminals showed no age-associated changes, the material was used to calculate parametric characteristics of Betz cells and associated terminals. Betz cell somata of the rhesus monkey were estimated to have a mean membrane surface area of 5,700 microns2. Axosomatic terminals on Betz cell somata had a mean appositional area of about 3.33 microns2 and covered about 15% of the somal surface. Thus, on average, each Betz cell appeared to receive approximately 260 axosomatic terminals. There were also some conspicuous age-associated changes in the motor cortex that were not quantified. These included an accumulation of lipofuscin and the presence of a novel inclusion body in the somata of Betz cells. Age-related occurrences in the neuropil included the degeneration of axons and their myelin, membrane-bound holes, and neuritic (senile) plaques.

Aging

Types of callosally projecting nonpyramidal neurons in rat visual cortex identified by lysosomal HRP retrograde labeling.

Callosally projecting neurons, labeled following injection of horseradish peroxidase (HRP) into the 17/18a border of the contralateral hemisphere, have been examined by light and electron microscopy. These neurons exhibit two types of horseradish peroxidase labeling: either a diffuse, Golgi-like labeling, or a granular, punctate labeling. The punctate type of HRP-labeling is the predominant form in nonpyramidal neurons, while pyramidal neurons frequently display either diffuse or punctate labeling. Only punctately labeled neurons have been examined in this study. Light microscopic analyses of 1-microns sections show that in the heavily labeled zone at the area 17/18a border approximately 9% of all of the cells in layer II/III are callosally projecting nonpyramidal cells, and 70% of them are callosally projecting pyramidal cells. Light and electron microscopic examinations indicate that the nonpyramidal neurons are a heterogeneous group which consists of small multipolar neurons, large multipolar neurons, small bipolar neurons, and large bipolar neurons. To investigate the ultrastructural appearance of the punctate HRP labeling, selected neurons have been examined in thin sections. In the electron microscope, the tetramethylbenzidine (TMB) reaction product appears as electron-dense crystals, while the diaminobenzidine (DAB) reaction product appears as dark, electron-dense material which fills the lysosomes. These lysosomes occasionally have a halo of reaction product, but often they are not morphologically distinguishable from dark lysosomes present within neurons from control animals in which the darkening results from staining the thin sections with lead citrate and uranyl acetate. However, labeled neurons possess more dark lysosomes than neurons from control animals. These additional dark lysosomes presumably contain the HRP reaction product visible by light microscopy.

Animals

Elevated lipoprotein(a) levels in patients with acute myeloblastic leukaemia decrease after successful chemotherapeutic treatment.

Twenty-two patients with acute myeloblastic leukaemia (AML) were studied to investigate disease-associated changes in lipid metabolism. Lipoprotein (a) [Lp(a)] levels were found to be elevated at the time of diagnosis (median 23 mg/dl; 41% of patient group had levels greater than 25 mg/dl) and diminished after successful chemotherapeutic treatment in 9 of 10 cases, with a maximum decrease from 56 to 10 mg/dl. In contrast, reduced levels of total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) (medians 137, 87 and 20 mg/dl, respectively) were observed at the time of diagnosis. Cholesterol and HDL levels increased in all 10 and LDL in 9 cases in which complete remission was achieved. These data suggest that the catabolism of LDL-cholesterol might be even more enhanced than assumed to date. Furthermore, it indicates that the Lp(a) level in acute myeloblastic leukaemia is influenced either directly or indirectly by the leukaemic blasts.

Adult

Complications of high tibial osteotomy and internal fixation with staples.

Osteotomy for osteoarthritis of the knee has established itself well since its first description by Jackson and Waugh [8, 9]. Internal fixation with staples allows early functional treatment with only a minimum of operative intervention. Removal of the metal is optional. In the 5-year period from 1986 to 1990, 182 high tibial osteotomies were performed at the Orthopaedic Department of the University Hospital of Freiburg. In four cases internal fixation was done with plates; in 178 cases two or more staples were used; in 3 cases a screw was additionally inserted for better hold. The staples became loose intraoperatively in eight cases (4.5%); only once did a dislocated staple have to be reoperated on post-operatively. Further complications which are independent of the method of internal fixation are summarized in the article. Complications of surgery on the long bones of the leg are inevitable, but with only one postoperatively dislocated staple and one case of non-infected pseudarthrosis (i.e. a method-related complication rate of 1.1%), internal fixation with staples for high tibial osteotomy presents itself as a reliable and safe procedure.

Adolescent

Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. III. Origins and frequency of occurrence of the terminals.

The cell bodies of the layer II/III pyramidal cells in rat visual cortex receive three morphologically distinct types of axon terminals. These axon terminals all form symmetric synapses and have been termed large, medium-sized, and dense axon terminals. The present study shows that each of these different kinds of axon terminals contains gamma-aminobutyric acid (GABA) which suggests that they are inhibitory. From an analysis of the profiles of 50 cell bodies it is calculated that the average layer II/III pyramidal cell has 65 axosomatic synapses, of which 43 are formed by medium-sized terminals, 10 by large terminals, and 12 by dense terminals. Comparison of these different kinds of axon terminals with labelled axon terminals of known origin suggests that the medium-sized terminals are derived from smooth multipolar cells with unmyelinated axons, and that at least some of the dense terminals originate from bipolar cells that contain vasoactive intestinal polypeptides. The source of the large axon terminals is not known, but it is suggested that they originate from multipolar non-pyramidal cells with myelinated axons. Since the initial axon segments of these same neurons receive GABAergic axon terminals from chandelier cells, at least four different types of neurons provide inhibition to the cell bodies and axons of layer II/III pyramidal cells. This serves as an illustration of the complexity of the neuronal circuits in which pyramidal cells are involved.

Animals

Osteopenia in rats with drug-induced mucopolysaccharidosis.

The immunostimulatory drug tilorone (CAS 27591-97-5) induces generalized lysosomal storage of sulfated glycosaminoglycans, i.e., mucopolysaccharidosis (MPS) in rats. Since inherited MPS of man is often associated with skeletal lesions the present study was performed to investigate whether the tilorone-induced MPS is also accompanied by bone alterations. The answer is yes. Rats (initial age 4 weeks) were orally treated with tilorone (60-80 mg/kg; 6-25 weeks). The proximal tibial metaphysis was examined by radiography and by light and electron microscopy. The tibiae of drug-treated rats remained smaller than those of pair-fed control rats. The primary bone trabecules in drug-treated rats became increasingly shorter, and the cortical bone became thinner. The general organization of the cartilaginous growth plate and the zones of vascular invasion and primary trabecule formation appeared similar as in control rats. Increased numbers of active osteoclasts were found at the free ends of the primary trabecules. Ultrastructurally, MPS-like alterations were observed in all types of bone cells. The osteopenia was partly reversible during recovery periods of more than 6 months after discontinuance of drug treatment. At present, the causal relationship between drug-induced MPS and osteopenia, as well as the mechanisms responsible for osteopenia are unknown. It is suggested that the principal factors are stimulation of osteoclasts and retardation, though not profound distortion, of the events involved in enchondral ossification.

Animals

Organization of pyramidal neurons in area 17 of monkey visual cortex.

In sections of area 17 of monkey visual cortex treated with an antibody to MAP2 the disposition of the cell bodies and dendrites of the neurons is readily visible. In such preparations it is evident that the apical dendrites of the pyramidal cells of layer VI form fascicles that pass into layer IV, where most of them gradually taper and form their terminal tufts. In contrast, the apical dendrites of the smaller layer V pyramidal cells come together in a more regular fashion. They form clusters that pass through layer IV and into layer II/III where the apical dendrites of many of the pyramidal cells in that layer add to the clusters. In horizontal sections taken through the middle of layer IV, these clusters of apical dendrites are found to have an average center-to-center spacing of about 30 microns, and it is proposed that each cluster of apical dendrites represents the axis of a module of pyramidal cells that has a diameter of about 30 microns and contains about 142 neurons. The MAP2 antibody reaction also reveals that some pyramidal cells in layers IVA and IVB have their cell bodies arranged into cones. There are about 118 such cones beneath 1 mm2 of cortical surface and the apical dendrites of the pyramidal cells within them bundle together at the apex of each cone to pass into layer III. Surrounding the cones of neurons there are horizontally aligned, thin dendrites. The location of these dendrites coincides with the dark walls of the honeycomb pattern seen in layer IVA after cytochrome oxidase reactions, or after the parvocellular input from the lateral geniculate nucleus has been labeled. Thus the cones of pyramidal cells within upper layer IV fit into the pockets of the honeycomb pattern. Below the cones of pyramidal cells are the outer Meynert cells within layer IVB, and the cell bodies of these large neurons are disposed so that they preferentially lie beneath the neuropil between the cones of pyramids. It is suggested that pyramidal cell modules are a basic feature of the cerebral cortex, and that these are combined together by afferent inputs to the cortex to generate the systems of functional columns.

Animals

Mutation pattern of immunoglobulin transgenes is compatible with a model of somatic hypermutation in which targeting of the mutator is linked to the direction of DNA replication.

We have previously demonstrated that B lymphocyte specific somatic mutations are introduced into the variable regions of immunoglobulin kappa transgenes in two independent transgenic mouse lines. The frequency, distribution and nature of these mutations strongly suggest that they arose as a result of the process of somatic hypermutation, which is responsible, in part, for affinity maturation during an immune response. Unexpectedly, in these multiple copy transgenic lines, many of the transgene copies showed no evidence of somatic mutation. This paradox was addressed by determining the sequence of each transgene copy in several B cell hybridomas derived from a mouse line carrying three copies of the kappa transgene. It was found that the somatic hypermutation process in different B cells from the same mouse preferentially targets one, but not the same, transgene copy. We present a model, based on the pattern of this targeting, which links somatic hypermutation to the orientation of the Ig gene relative to the direction of DNA replication.

Animals

Human recombinant dimeric IL-6 binds to its receptor as detected by anti-IL-6 monoclonal antibodies.

Three different epitopes of the human IL-6 (IL-6) molecule were recognized by the mAb B-E4 (IgG2b), B-E8 (IgG1) and B-F6 (IgG1). The affinities of these three mAb for IL-6 differ little in several assays but if ranked by affinity they fall into the following order B-E8 greater than B-E4 greater than B-F6. B-E4 and B-E8 mAb, recognizing two different epitopes, are inhibiting mAb in the bioassay with the IL-6 depending cell line B9, however B-E8 has an inhibiting activity higher than B-E4. Both human natural IL-6 (HnIL-6) and human recombinant IL-6 (HrIL-6) were inhibited but not the murine natural IL-6 (MnIL-6). Surprisingly, not only the non-inhibiting mAb (B-F6) recognizes the HrIL-6 fixed to the receptor but also the inhibiting mAb B-E4 and B-E8. This together with the results obtained in a sandwich ELISA where the same mAb was used as both catcher and tracer to detect HrIL-6, it was concluded that dimeric HrIL-6 is able to fix the IL-6 receptor. Competition studies between monomeric HnIL-6 and dimeric HrIL-6 showed that the affinity of the dimeric HrIL-6 for the receptor was higher than that of HnIL-6.

Animals

A technique for estimating total spine numbers on Golgi-impregnated dendrites.

The functional significance of dendritic spines and their morphological sensitivity to a wide spectrum of experimental manipulations and pathological states have led to a number of studies in which counts of dendritic spine number have been carried out. These studies have, for the most part, involved the enumeration of only those spines which protrude from the opaque shafts of Golgi-impregnated dendrites into the clear zones flanking the dendrite. Such counts, limited to only those spines which are visible, underrepresent the true total number of spines borne by the dendrites. The magnitude of underrepresentation correlates positively with dendritic shaft diameter and negatively with spine length. This seriously restricts the usefulness of comparisons of spine density between dendrites, or even between segments of the same dendrite. In the present report, a geometrically based method is presented whereby total dendritic spine numbers can be estimated with reasonable accuracy, taking into account factors such as dendrite diameter and spine length. The technique entails the following principal steps: a determination, for a given length of dendrite over which spines are to be enumerated, of the volume of the flanking zones in which spines are visible and can be counted; a determination of the volume of the entire zone which encircles the dendritic shaft and which contains all spines, both visible and not visible; and a proportional extrapolation from the number of visible spines to obtain an estimate of the true total spine number. Tests of the predictive accuracy of the technique using dendrites of known total spine number suggest that estimates which deviate from true total spine numbers by less than 10% can be achieved.

Animals

[Epidemiology of hepatitis A: serological study among a French population (author's transl)].

To investigate the prevalence and distribution of antibodies to hepatitis A antigen (anti HAV Ab) we tested 848 French people living mainly but not exclusively in Franche-Comté (East of France). In Franche-Comté, 76 per cent of all the subjects studied were found to be anti-Hav ab positive, as determined by specific radio-immuno-assay. The rate of antibody detection was correlated with age; the prevalence was low (38 per cent) in childhood and adolescence, gradually increasing throught adulthood, and reaching its peak level (greater than 95 per cent) in people aged 40 and above. Anti-HAV Ab was detected more frequently in farmers (89 per cent), factory workers (87 per cent) and office employees (80 per cent) than in hospital personnel (53 per cent). Socioeconomic differences were found to be important in young people but tended to disappear at about 40 years of age. No difference was found in the prevalence of anti-HAV Ab between national servicemen from Franche-Comté and those from other regions. In 3 per cent of cases anti-HBs Ab was associated with the presence of anti HAV Ab. The subject possessing anti HBS Ab had the same prevalence of anti-HAV Ab (75 per cent) as those without (76 per cent).

Adolescent

The bilaminar and banded distribution of the callosal terminals in the posterior neocortex of the rat.

After callosal sectioning, the callosal connections of the posterior neocortex of the rat cerebral hemisphere were demonstrated using the Fink-Heimer technique. Serial frozen sections of the whole brains were cut in transverse, horizontal, and tangential planes. In tissue sections, degenerating terminals were concentrated in two distinct laminae within the depth of the cortex. In addition the terminals had a patchy distribution. The degeneration was marked on projection drawings of serially arranged sections, and subsequent reconstruction showed the terminal degeneration to be distributed in bands. Five dorsoventrally oriented bands of terminals were present in areas 39, 41 and 36 collectively, and a rostrocaudal band in area 20. In area 17 terminations were apparently absent except at its borders with areas 18, 18a and 7. The degenerating callosal terminals within these areas produced a circumferential band around area 17. The findings are discussed with respect to the significance of these patterns of corticocortical connections.

Afferent Pathways

The choroid plexus of the mature and aging rat: the choroidal epithelium.

The choroid plexus of mature and old rats has been examined by both scanning and transmission electron microscopy. It has been shown that the macrophages lying upon the ventricular surface of the choroid plexus have a close association with burr-like protrusions that extend from the apical surfaces of the choroidal epithelial cells. These protrusions have a dark cytoplasm filled with vesicles and tubules, and projecting from them are thin, shrunken microvilli. It is suggested that these protrusions are phagocytosed by the macrophages and that they are the source of some of the inclusions which become increasingly common within the cytoplasm of macrophages in older rats. The lateral surfaces of the choroidal epithelial cells have also been examined in the scanning electron microscope after exposure of the surfaces by dissection. In such preparations it is apparent that the elaborate interdigitations between adjacent cells are effected by irregular and vertically arranged folds confined to the basal portions of the lateral cell surfaces. Lastly, it has been shown that at the junction between the choroid plexus and the ependyma in the lateral ventricle, there are two modes of transition between the choroidal and ependymal epithelia. In one, typical choroidal and ependymal epithelial cells lie next to each other to produce a distinct and continuous bondary. In the other mode the boundary is also continuous, but there are modified ependymal cells present. These modified cells have short, relatively sparsely distributed microvilli and not more than one or two cilia.

Aging

The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex. V. Degenerating axon terminals synapsing with Golgi impregnated neurons.

The sites of termination of afferents from the lateral geniculate nucleus to layer IV and lower layer III in area 17 of the rat visual cortex have been determined by use of a combined degeneration--Golgi/EM technique. Degeneration of geniculocortical axon terminals was produced by making lesions in the lateral geniculate body. After the animals had been allowed to survive for two days, the ipsilateral visual cortex was removed and impregnated by the Golgi technique. Suitably impregnated neurons and their processes in layer IV and lower layer III were then gold-toned and deimpregnated for examination in the electron microscope. A search was made for synapses between degenerating axon terminals and the gold-labelled postsynaptic neurons. Geniculocortical synapses were found to involve: (1) the spines of basal dendrites as well as those of proximal shafts and collaterals of apical dendrites of layer III pyramidal neurons; (2) the spines of the apical dendritic shafts and collaterals of layer V pyramidal neurons; (3) the perikaryon and dendritic spines of a sparsely-spined stellate cell; and (4) the perikaryon and dendrites of a smooth, bitufted stellate cell. In view of this variety of postsynaptic elements it is suggested that all parts of the perikarya and dendrites of neurons contained in layer IV and lower layer III which are capable of forming asymmetric synapses can be postsynaptic to the thalamic input. Finally, an analysis of the known neuronal interrelations within the rat visual cortex is presented.

Afferent Pathways