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Biomedical subjects

A Peters

Publications and source records attributed to A Peters.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

[Anti-basal membrane glomerulonephritis after homologous kidney transplantation in hereditary Alport's nephropathy].

A patient, born in 1968, was found at the age of 9 years to have Alport's syndrome. In his 20th year, when in terminal renal failure, his father's kidney was transplanted into him. 14 months later there was a sudden worsening of his renal function after a varicella infection; for the first time antibodies against the glomerular basal membrane (GBM) were detected. Despite an increase in prednisolone dosage and 6 plasmaphereses chronic haemodialysis again became necessary. Renal biopsy revealed necrotizing intra- and extracapillary glomerulonephritis. Simultaneously there was a raised anti-NC-1-antibody titre (1:80) in the serum. After removal of the transplant the titre fell to normal. The NC-1 antigen, a component of the GBM in healthy persons, may be absent in Alport's syndrome. An analysis of the few cases of anti-GBM glomerulonephritis in renal transplants of patients with Alport's syndrome may make it possible to recognize factors which precipitate or favour this form of glomerulonephritis.

Adult↗
PubMed1991

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↗
PubMed1991

Effects of aging on the neuroglial cells and pericytes within area 17 of the rhesus monkey cerebral cortex.

An electron microscopic analysis has been carried out to compare the neuroglial cells and pericytes within the primary visual cortex, area 17, of young (5-6 years) and old (25-35 years) rhesus monkeys. All of the neuroglial cell types accumulate inclusions within their cytoplasm as they age, and the inclusions within the astrocytes and oligodendrocytes are essentially characteristic of those cell types. The astrocytes probably acquire their inclusions by phagocytosis, and it is suggested that the inclusions in the oligodendrocytes are caused by an age-related degeneration of the myelin sheaths they produce. The inclusions within the microglia are very heterogeneous. They are more massive than in the other neuroglial cells, so that their inclusions may almost fill the microglia. Pericytes also accumulate inclusions with age and there is evidence to suggest that they empty the contents of their inclusions vacuoles directly into the capillaries. On the basis of counts of the numbers of profiles of neuroglial cells displaying nuclei in thin sections, the only cells to increase in number with age are the microglia. They show an increase of about 44% when the cortices of young and old monkeys are compared.

Aging↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Soluble interleukin-2 receptors in chronic renal failure.

A depression of the general immune response in uremia is well documented, and hemodialyzed (HD) patients present deficient interleukin-2 (IL2) secretion. Since soluble IL2 receptors (SIL2R) could affect the immune response through interaction with circulating immune cells, we studied the potential relationship between SIL2R concentration and lymphocyte subsets in 44 HD patients. HD patients present lymphopenia, higher CD4/CD8 ratio. CD16 counts and SIL2R concentrations than controls. A significant negative correlation was found between SIL2R concentration and lymphocyte count (p less than 0.01), and between SIL2R concentration and T4/T8 ratio (p less than 0.01). An increase of SIL2R concentration due to abnormal T cell preactivation in HD patients with nonreused cuprophan membranes could perhaps contribute to cell immunity impairment through IL2 binding and inhibition of T cell activation.

CD4-CD8 Ratio↗
PubMed1991

Clinical evaluation of decision support system for insulin-dose adjustment in IDDM.

OBJECTIVE: We developed a wallet-sized learning memory decision support system that helps patients with insulin-dependent diabetes mellitus adjust their insulin dosages. RESEARCH DESIGN AND METHODS: To determine the efficacy of the support system, we designed a randomized clinical trial with patients participating in a program in a diabetes education center. Patients were assigned to two groups of 21 patients each. All patients performed self-monitoring of blood glucose (SMBG) and were treated with multiple daily injections of insulin. Each of the patients was examined over a 32-day period. The basic educational program, i.e., practical advice in SMBG, diet, and exercise under homelike conditions, was identical in both groups. The only difference was that the first group used the computer for adjusting the insulin dose, whereas the second group received recommendations from the education team. RESULTS: The baseline HbA1 levels (9.8 +/- 1.6 vs. 9.9 +/- 1.6%) of both groups did not differ significantly. Mean blood glucose over the last 2 wk of the study was higher (P less than 0.01) in the second group (8.4 +/- 1.4 vs. 9.2 +/- 2.0 mM); the frequencies of hypoglycemic episodes were not different (1.7 vs. 2.3%). CONCLUSIONS: Metabolic control and safety were comparable in both groups. Thus, patients may benefit from such a system at home where no support by diabetes educators is available.

Adult↗
PubMed1990

Transcallosal non-pyramidal cell projections from visual cortex in the cat.

Non-pyramidal cells with transcallosal projections were identified in the area 17/18 border region of the cat by retrograde transport of horseradish peroxidase injected into border region of the opposite hemisphere. From several hundred neurons filled with a Golgi-like diaminobenzidine (DAB) reaction product, seven cells were identified by their radially oriented smooth dendrites as possible non-pyramidal cells. Following thin-sectioning and examination with the electron microscope, four of the neurons proved to be layer IV spiny stellate cells with incompletely filled dendritic spines, and two proved to be layer III pyramidal cells with an incompletely labelled apical dendrite and dendritic spines. The remaining neuron was a non-pyramidal cell whose essentially smooth dendrites were covered with synapses, and whose cell body formed both symmetric and asymmetric synapses with presynaptic terminals. To better assess how many non-pyramidal cells might be labelled, thin sections of the area 17/18 border were surveyed using material processed with tetramethylbenzidine (TMB), and another five labelled non-pyramidal cells with transcallosal projections were identified by the needle-like crystals of TMB reaction product they contained. During the study it became evident that both the DAB and TMB reaction products in the lightly labelled neurons tended to be associated with granules that are 0.5 microns or larger in diameter and that had the characteristics of lysosomes. These granules are also visible in the light microscope as dark puncta. The numbers of puncta in profiles of pyramidal and of non-pyramidal cells in layers II/III and IVa of the area 17/18 border region and in the control acallosal region of area 17 were counted and compared. These comparisons revealed that labelled transcallosally projecting non-pyramidal cells may constitute 10-32% of the non-pyramidal cell population at the area 17/18 border region. Similar values were also obtained for pyramidal cells in this region. Consequently, it is concluded that significant numbers of non-pyramidal cells have axons that project through the corpus callosum to the contralateral hemisphere.

Animals↗
PubMed1990

Morphological evidence for callosally projecting nonpyramidal neurons in rat visual cortex.

This investigation shows that some of the callosally projecting neurons in rat visual cortex are nonpyramidal cells. Callosally projecting neurons were labeled by injections of horseradish peroxidase (HRP) into the area 17/18a border zone of the contralateral hemisphere. The retrogradely transported HRP was visualized with diaminobenzidine or with tetramethylbenzidine. In some of the labeled neurons the reaction product was diffuse, so that the neurons had a Golgi-like appearance, but in others the reaction product was granular, or punctate. The majority of neurons with a Golgi-like appearance were pyramidal cells, but one callosally projecting neuron from layer V area 18a was confirmed by electron microscopy to be a nonpyramidal neuron. This dearth of well-filled nonpyramidal cells suggested that callosally projecting nonpyramidal neurons may not transport sufficient HRP to show Golgi-like filling, and so punctately labeled neurons from areas 17, 18a and 18b were examined. Reacted sections from areas 17, 18a and 18b of control animals, into which no tracer had been injected, were also examined, but in these control preparations no granules similar to the HRP granules within the neuronal profiles of the experimental animals were encountered. In methylene blue-stained 1-microns sections, neuronal profiles from the control animals possessed only blue staining lysosomes, while neuronal profiles from the experimental animals exhibited both lysosomes and HRP granules. It was determined, from the counts of HRP granules in neurons from the experimental animals, that in selected regions of areas 17, 18a, and 18b similar percentages of the pyramidal and nonpyramidal neuronal populations (ranging from 100% to 34%) contained HRP granules, and so had callosally projecting axons. However, most callosally projecting nonpyramidal neurons had far fewer HRP granules than the pyramidal neurons, again indicating that they transport less HRP. This could account for the fact that callosally projecting nonpyramidal neurons only rarely show a Golgi-like filling, and this could be one reason why such cells have been overlooked in most previous studies.

Animals↗
PubMed1990

The axon terminals of vasoactive intestinal polypeptide (VIP)-containing bipolar cells in rat visual cortex.

In vasoactive intestinal polypeptide (VIP)-immunoreacted preparations, bipolar neurons are the cells most commonly labelled. The VIP-positive axon terminals form symmetrical synapses, and their most common postsynaptic targets are small and medium sized dendrites. These are of both smooth and spiny types. Additionally, there is a concentration of VIP-positive axon terminals around the cell bodies of pyramidal neurons, and it is suggested that an important function of VIP-labelled bipolar cells is to inhibit vertically oriented groups of pyramidal cells. In order to further examine the features of axon terminals that label with VIP antibodies, conventionally prepared material was examined by electron microscopy. Those terminals which label with VIP antibody are characterized by irregular profiles of varying sizes and shapes, and by containing closely packed pleomorphic vesicles. Such terminals form symmetrical synapses. The junctions are not well marked by associated cytoplasmic densities, but there is an inherent density within the synaptic cleft. It is suggested that these features characterize all axon terminals in which GABA coexists with peptides in cerebral cortex.

Animals↗