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Biomedical subjects

A Peters

Publications and source records attributed to A Peters.

At least 235 records · Page 13Linked to original sources

Proliferation of thalamic afferents in cerebral cortex altered by callosal deafferentation.

In area 41, the auditory region of rat neocortex, callosal afferents project to layers I through III and thalamic afferents project to deep layer III through IV. Thus, these two extrinsic systems of afferents project simultaneously to only a narrow lamina in mid to low layer III. For this study, this narrow region of overlap is quantitatively examined to determine the distribution of callosal and thalamic afferents by observing degenerating terminals produced by separate callosal and thalamic lesions. The results show that of all asymmetric synapses observed in the neuropil of this narrow zone, 84% are dendritic spines and the balance are dendritic shafts. Although both callosal and thalamic afferents prefer to synapse with dendritic spines in the neuropil, 78% of the thalamic afferents synapse with dendritic spines while 93% of the callosal afferents synapse with dendritic spines. Vaughan & Foundas (1982) have shown that 3 months after callosal lesions in 1-month-old animals, additional thalamic axons have grown into, and proliferated in, this part of mid to low layer III. Quantitative analysis of the distribution of the degenerating thalamic axon terminals in these long-term callosally lesioned animals has been used to determine whether the proliferating thalamic afferents demonstrate any specificity in the pattern of synapses they make or whether the callosally deafferented neurons determine the pattern of synapses. The results indicate that thalamic axons do exhibit axon specificity, for after they have proliferated into the callosal domain, 80% of the degenerating terminals synapse with dendritic spines and 20% synapse with shafts. This distribution is most comparable to the normal distribution of thalamic axons in this region.

Animals↗

Toxic responses to acute, subchronic, and chronic oral administrations of monochlorobenzene to rodents.

Acute (single exposure), 14-d repeated exposure, 91-d subchronic, and 103-wk chronic toxicity studies of orally administered (gavage, in corn oil) monochlorobenzene were conducted in male and female Fischer-344 rats and B6C3F1 hybrid mice. A single exposure to 4000 mg/kg was lethal to male and female rats, while a single exposure to a dose as low as 1000 mg/kg was lethal to mice. Fourteen daily exposures to 1000 mg/kg caused death in rats of both sexes, but neither survival nor clinical health were compromised at 500 mg/kg in rats or mice. In the 91-d studies, wherein monochlorobenzene was administered once daily, 5 d/wk, survival was reduced by doses of 500 mg/kg and higher in rats, and by doses of 250 mg/kg and higher in mice. Dose-dependent necrosis of the liver (hepatocytes), degeneration or focal necrosis of the renal proximal tubules, and lymphoid or myeloid depletion of the spleen, bone marrow, and thymus (mild to severe) were produced by doses of 250 mg/kg or greater of monochlorobenzene in both sexes of rats and mice, although the incidences of these lesions varied considerably by sex and species. Consistent changes in the circulating blood components were not observed, but a mild porphyrinuria was detected at the higher doses. No toxic effects were observed at doses of 125 mg/kg or less. In the 2-yr studies, wherein monochlorobenzene was administered once daily, 5 d/wk, doses of 30 or 60 mg/kg in male mice and 60 or 120 mg/kg in female mice and male and female rats did not produce any evidence of toxicity. Doses of 60 or 120 mg/kg caused slight (statistically significant at 120 mg/kg; p less than 0.05) increases in the frequencies of male rats with neoplastic nodules of the liver. Increased tumor frequencies were not observed in female rats or in male or female mice receiving monochlorobenzene.

Administration, Oral↗

Removal of marrow T cells with OKT3-OKT11 monoclonal antibodies and complement to prevent acute graft-versus-host disease. A pilot study in ten patients.

We studied the feasibility of T cell depletion of bone marrow for transplantation in preventing acute graft-versus-host disease GVHD in patients having a high risk of acute GVHD. We report our preliminary clinical experience of the ex-vivo treatment of allogeneic marrow using a pan-T monoclonal antibody combination (OKT3-OKT11) plus baby rabbit complement. Ten patients received allografts from HLA-identical sibling donors. All patients had malignant hematological disease with poor prognosis (6 acute leukemia, 3 chronic granulocytic leukemia, and 1 multiple myeloma). Nine patients were at high risk of acute GVHD (older than 30 years for 4 patients, chronic granulocytic leukemia in acute or accelerated phase for 3, and acute leukemia in relapse for 2). Posttransplant management with methotrexate was maintained until day 100 in the first four patients and stopped at day 11 for the six others. The ex-vivo treatment with the OKT combination and complement removed 88.3% +/- 11.8 of the T lymphocytes. The myeloid progenitors recovered at the end of the procedure showed a moderate effect of monoclonal antibodies and complement (75.8% +/- 12.2). Engraftment was achieved in all patients: 23.3 days +/- 5.10 to reach 0.5 X 10(9) granulocytes per liter and 31.5 days +/- 12.2 to reach 50 X 10(9) platelets per liter. No acute GVHD was observed in this group of patients. Of the 10 patients, 7 are alive and well and have been in continuous remission from 2-10 months. Three patients have relapsed.

Adolescent↗

Maternal height and shoe size as predictors of pelvic disproportion: an assessment.

A total of 351 women who gave birth in the Paddington and North Kensington Health District were studied in order to establish a factual basis for recording height and shoe size as indicators of pelvic adequacy. Because only 19 women had radiological pelvimetry assessment, type of delivery and length of labour were used as proxy measures of disproportion. Of the 57 women with a shoe size less than 4 1/2, 21% were delivered by caesarean section compared with 10% of the group with shoe size between 4 1/2 and 6 and only 1% of the group with shoe size greater than or equal to 6 1/2. Similar relations with height were not generally found. The data were further examined using logistic regression models of the expected percentages of mothers having an adverse delivery. The models confirmed and extended the more simple analysis.

Body Height↗

Magnetic resonance imaging in hemosiderosis.

The case of a patient with iron deposition disease is presented to illustrate the value of magnetic resonance imaging (MRI) in the evaluation of this entity. The image characteristics of MRI are discussed and the results are compared with those of computer tomography (CT). The importance of a decrease in T2 relaxation time as the determinant parameter for signal intensity in MRI of the liver in such patients is emphasized.

Female↗

Simplified evaluation and documentation of data from glucose controlled insulin infusion systems--artefact handling.

A computerized method for artefact handling, which occurs during recording and evaluation of data from glucose controlled insulin infusion systems (GCIIS) is demonstrated: Recording phase: "Interrupt"-Mode: Restoring of the original linear data-time relation is achieved by using an additional time channel. Analogous treatment of time- and parameter files allows correct correlation. "Communication I/O error": An error-handling subroutine prevents break of program caused by lead characters which occur during restarting the GCIIS thereby disturbing GCIIS-microcomputer communication. Risk of data loss caused by breakdown of electric current is minimized by an appropriate interaction between intermediate store and floppy disk for data transfer. Evaluation phase: Implausible data: Obstruction of double lumen catheter as well as loss of glucose sensor sensitivity result in inappropriate data with consecutive incorrect computation of glycemic indices such as MAGE and M-value. Zero-values: During "HOLD"-mode, all blood glucose values are set to zero by the GCIIS causing forbidden arithmetic operations. These artefact periods are marked in the prepared time-file, deleted and interpolated subsequently. In conclusion, our method permits automatic artefact handling during the recording phase and complete correct data processing during the evaluation phase.

Blood Glucose↗

Evaluation of two new filtration systems--Fenwal PS400 and Organon Teknika Curesis--and comparison of results with two centrifugation systems--IBM model 2997 and Haemonetics V50.

Two new filtration systems (Fenwal CPS 10TM - PS 400 and Organon Teknika Curesis - M82) were evaluated and compared with two centrifugal cell separators (IBM 2997 and Haemonetics V50). 11 patients with auto immune diseases and dermatological diseases underwent 230 consecutive plasma exchanges. For the filtration systems, the average whole blood rate was 50 ml/min and the plasma separation rate was about 21 ml/min for a transmembrane pressure about 70 mmHg. The pre/post percent reduction and sieving coefficient were calculated for some plasma and blood components. A variety of laboratory studies was monitored to assess the efficacy of plasma separators, their biocompatibility and some yields. These results show that the 2 filters appear safe and efficacious but their modules are too simple and do not offer a great security (no transmembrane pressure control or no extracorporeal fluid balance). For a blood banker, IBM 2997 seems more interesting if we take in account its characteristics during plasma exchanges and the possibility which is offered to carry out cytapheresis procedures. But for a thrombopenic patient the filtration systems keep their advantages.

Autoimmune Diseases↗

Differentiation of algal chemoreceptors. A comparative receptor study with two seaweed pairs: Cutleria multifida/Syringoderma phinneyi and Desmarestia aculeata/Ectocarpus siliculosus (Phacophyceae).

Gamete encounter in the reproduction of brown algae is supported by lures produced by the female cells. These signals are low-molecular-mass, volatile, olefinic hydrocarbons. Specific receptors on the motile male gametes recognize the pheromones at threshold concentrations as low as 6.5 pmol/l. The pheromones are possibly bound by dispersion and dipolar interactions. Tight fitting has to compensate for these weak contact forces. This causes strong chiral discrimination (relative affinities to enantiomeric lures 1:100). Structurally related messengers with identical substitution patterns and overall space filling are mutually distinguished in several species by means of altered topologies in their receptor mould. Responses to systematically varied synthetic bis-alkenyl-cyclopentene pheromones showed that the sensors of Syringoderma and Cutleria androgametes consist of a mosaic of attachment sites individually adapted to specific structural elements in the messenger molecule. They may be permutated to afford optimal binding. An alternative strategy: distinct reading of electron density combined with variation of sensitivity, brings about 'fidelity' in signal transmission by the alkylated cycloheptadiene pheromones in two species of Desmarestia and Ectocarpus. Inhibition of chemotaxis by ectocarpene is observed in Ectocarpus males in the presence of desmarestene, the lure of Desmarestia, and related parapheromones. This indicates complex interactions between different species of algae sharing a common habitat, in their defense of living space.

Animals↗

Autologous bone marrow transplantation for acute leukemia using transplant chemopurified with metabolite of oxazaphosphorines (ASTA Z 7557, INN mafosfamide). First clinical results.

The contamination of autologous marrow with clonogenic tumor cells has been the main argument against ABMT in acute leukemia. In a preclinical study we evaluated an active cyclophosphamide derivative named "ASTA Z 7557". We observed that the toxic effect of this drug on CFU-GM growth was dependent on nucleated cell concentration as well as on red blood cell contamination. The potency of the drug was in close relationship with the incubation temperature. The growth of leukemic CFU was inhibited with an ASTA Z dose higher than 30 micrograms/ml. In our system, beyond 40 micrograms/ml more than 95% of committed stem cells are destroyed. Fifteen patients had autotransplant because of AML for 10 patients and because of ALL for 5 patients (4 patients were grafted in relapse and 11 patients in remission). We demonstrated that the marrow take was possible although the inoculum is CFU-GM depleted. Five of the 10 AML patients are alive and remain disease-free at 45+, 65+, 190+, 345+ and 570+ days from ABMT without any maintenance treatment. Four of the 5 ALL patients are alive, three of them in complete remission (40+, 110+, 250+ days). The number of patients reported in this clinical study was relatively small and more cases should be evaluated to be conclusive. Nevertheless the feasibility of chemopurified ABMT was demonstrated.

Adult↗

The pattern of the mononuclear infiltrate as a prognostic parameter in flat superficial spreading melanomas.

The mononuclear cell infiltrate of 90 superficial spreading melanomas (SSM) of less than or equal to 1.5 mm thickness was analyzed at different locations around and within the tumors. All patients had been followed for at least 5 years, and 20 (22%) had developed metastases. A correlation between the overall inflammatory response in the histologic sections and the prognosis was not observed, nor could a significant distinction be made between metastasizing and nonmetastasizing melanomas when the mononuclear cell infiltrate was analyzed at different locations. A significant clustering of metastasizing tumors was, however, observed in the subgroup with a relatively strong infiltrate within the tumor compared with the overall infiltrate. From this observation, a semiquantitative description of the pattern of the infiltrate was established. It provides an additional parameter for prognostication in flat SSMs and it raises new questions about the role of the local host-tumor interaction.

Adult↗

Colour and photosensitive epilepsy.

Red-coloured flicker is claimed to be more epileptogenic than white or that of other colours matched for subjective intensity. A feature of the colour opponent system is that the response of luminosity-sensitive cortical units to stimulation of ganglion cells of a particular spectral sensitivity is reduced when cells of other sensitivities are simultaneously stimulated. We hypothesized that the apparent effect of colour on photosensitivity was not a property of red light per se but arose simply from the fact that, with commercially available filters a light can be provided to stimulate only red sensitive cones, but owing to the overlap of the absorption spectra of the visual pigments it is difficult to stimulate only green or blue sensitive cones. Such stimulation of a single cone population can be achieved by the 'silent substitution method' which has been used for evoked response studies. In 12 photosensitive epileptic patients we find that, using stimulus intensities (less than 20 nits) at which white flicker is without effect, stimulation of either red or green cones by the silent substitution method may produce epileptiform discharges, there being a slight (and not significant) excess of patients showing a greater sensitivity for green than for red cone stimulation. The findings are considered to support the hypothesis set out above.

Color Perception↗

Vasoactive intestinal polypeptide-immunoreactive neurons in rat visual cortex.

An antibody to vasoactive intestinal polypeptide (VIP) was used to examine the forms of VIP-positive neurons and the synapses made by VIP-positive axon terminals. Vasoactive intestinal polypeptide-positive cells are most common in layers II and III and the majority of them are typical bipolar neurons, with two primary dendrites which emanate from the upper and lower poles of the cell body. Their somata, which have only a few symmetric and asymmetric synapses, generally have a fusiform or "tear-drop" shape and contain nuclei with a vertically oriented cleft. The dendritic trees are arranged vertically and often extend through five cortical layers. The axons are thin and extend either from the soma or from one of the primary dendrites. The axons also follow a vertical trajectory. Other VIP-positive neurons are modified bipolar cells and a few of them are multipolar cells. The synapses formed by the VIP-positive axon terminals in the neuropil are symmetric in form, and although the synaptic clefts are narrow, the junctions are usually long and continuous, rather like those described for asymmetric synapses. Most of the VIP-positive axon terminals synpase with small dendritic shafts, but a few synapse with neuronal cell bodies. Since the majority of the VIP-positive neurons are bipolar cells it is concluded that these are the source of most of the VIP-positive axon terminals. If this is so, then the VIP-positive bipolar cells form symmetric synapses. This is in contrast to the observations of Peters and Kimerer (1981. J. Neurocytol. 10, 921-946) for the bipolar cells they examined in a Golgi-electron microscopic study had axon terminals forming asymmetric synapses. It is suggested that this disparity can be reconciled if it is assumed that the bipolar cell population consists of subgroups which have different biochemical characteristics and different synaptic relationships.

Animals↗

Attempts to combine 2-deoxyglucose autoradiography and tyrosine hydroxylase immunohistochemistry.

The possibilities were analysed to combine the 2-deoxyglucose technique and indirect immunofluorescence histochemistry using tyrosine hydroxylase antiserum, with the aim to study functional activity in immunohistochemically characterized single neurons. Since the product measured with the 2-deoxyglucose method is water soluble and since immunohistochemistry requires that sections repeatedly run through aqueous media, the 2-deoxyglucose method was carried out before fixation and immunohistochemistry. The routine rapid thaw-mounting at + 60 degrees C of sections for 2-deoxyglucose autoradiography was found not to be compatible with immunohistochemistry. Instead a new mounting technique based on "gluing" the sections on to the object slide with a mixture of a standard mounting medium (Permount) and xylene was used to avoid diffusion at this stage. Two procedures were outlined, both starting with unfixed brains cut on a cryostat. In Method I autoradiographic sheet film was used. After autoradiographic exposure, the section was immersion-fixed in formalin, processed for immunohistochemistry, analysed and photographed in a fluorescence microscope and the results compared with the autoradiographic distribution patterns on the film. However, only the low resolution of the routine 2-deoxyglucose technique was obtained, which did not allow analysis of activity in single cells. In Method II, liquid emulsion applied by the loop technique was used. After exposure, autoradiographic developing and fixation, dehydration, mounting, analysis and photography of autoradiographs in the light microscope, the cover-slip was removed, the sections rehydrated and processed for indirect immunofluorescence histochemistry. With this procedure single autoradiographically labeled cells were observed, some of which contained tyrosine hydroxylase. Thus, with Method II it may in the future be possible to monitor functional activity in single immunohistochemically identified neuronal cell bodies. In order to obtain a useful and reliable method for this purpose, however, further extensive work with regard to, for example, quantification will be required.

Animals↗