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Biomedical subjects

M Wassef

Publications and source records attributed to M Wassef.

At least 127 records · Page 7Linked to original sources

Non-Purkinje cell GABAergic innervation of the deep cerebellar nuclei: a quantitative immunocytochemical study in C57BL and in Purkinje cell degeneration mutant mice.

Purkinje cell degeneration (pcd) mutant mice, 3-4 months old, were used to identify and quantify the non-Purkinje cell GABAergic innervation of deep cerebellar nuclei. Glutamic acid decarboxylase (GAD) immunoreactive structures appeared as dark dots throughout the 4 nuclei. Ultrastructural examination confirmed that each dot corresponded to an axon terminal. GAD-labeled boutons were large, contained tightly packed flattened vesicles and established Gray type II synapses with all nuclear neuronal populations. Thus, cytological criteria did not distinguish between Purkinje cell and non-Purkinje cell GAD-positive nerve terminals, since they shared many common features. The number of GAD-immunoreactive axon terminals in the deep nuclei of pcd cerebella was compared to that of normal C57BL mice. Despite an almost complete disappearance of Purkinje cells in the pcd mouse (less than 0.05% of these neurons remained in the mutants), the surface density of GAD-positive nerve terminals in the deep nuclear region was 37% of control value. Taking into account a volumetric decrease of 58% for the deep nuclei of the mutant cerebellum, we estimated the percentage of GAD-positive boutons innervating these nuclei to be 15% of normal values. This important residual innervation of the deep nuclei might arise from local GABAergic neurons, which were identified in the normal and mutant cerebella by immunostaining with an anti-GABA antibody.

Animals↗

Localization of glutamic-acid-decarboxylase-immunoreactive axon terminals in the inferior olive of the rat, with special emphasis on anatomical relations between GABAergic synapses and dendrodendritic gap junctions.

Immunocytochemical and electron microscopic methods were used to examine the GABAergic innervation of the inferior olivary nucleus in adult rats. This neuronal system was visualized with an antibody against glutamic acid decarboxylase (GAD, EC 4.1.1.15), the GABA-synthesizing enzyme. A GAD-positive reaction product was encountered only in short segments of preterminal axons and in axon terminals. Their relative number per unit area of neuropil was very similar in all olivary subnuclei. Despite this homogeneity in density, obvious intraregional differences existed. Some regions were strongly immunoreactive (the "c" subgroup, the beta nucleus, and the mediolateral outgrowth of the medial accessory olive), whereas others were weakly labeled (the dorsomedial cell column and the central zones of the medial accessory and principal olives). The strongly immunoreactive areas contained the largest and most intensively labeled axon terminals. Areas of weak labeling were filled with small, weakly immunoreactive nerve terminals. Thus, variations in size and in intensity of labeling create a specific pattern of GABA innervation, revealed by an almost continuous gradient between the above-mentioned extremes. The GAD-positive axon terminals established conventional synapses with dendrites (94% of the samples) or with cell bodies (6%). The vast majority of these synapses were type II (84%) and only a small proportion formed type I synaptic contacts (16%), regardless of the nature of the postsynaptic element. Immunoreactive terminals were also involved in the complex synaptic arrangements--the glomeruli, which characterize the olivary neuropil. Within these formations, olivary neurons were electrotonically coupled through dendrodendritic gap junctions. There was a constant association between GAD-positive axon terminals and small dendritic appendages linked by gap junctions. This association was revealed not only by the systematic presence of immunolabeled terminals directly apposed to the dendritic appendages but, more importantly, by the frequent presence of type II synapses straddling both elements. These synapses were in close proximity to the low-resistance pathways represented by the gap junctions. The strategic location of these GABA synapses is discussed in relation to recent findings indicating the possibility of a synaptic modulation of the electrical coupling: the release of GABA, by increasing nonjunctional membrane conductance, could shunt the coupling between olivary neurons. The functional decoupling of selected gap junctions would be responsible for the spatial organization of the olivary electrotonic coupling.

Animals↗

The influence of D.D.A.V.P. on the survival of factor VIII in severe haemophiliacs.

The effect of D.D.A.V.P. (desamino-cys'-D-arg8-Vaso-pressin) on the survival characteristics of transfused VIII concentrate was studied in six severe, adolescent, haemophiliacs (VIII:C 1 iu/dl). D.D.A.V.P. was administered at a concentration of 0.3 ug/kg immediately following or 24 hours post infusion. No significant alteration in the half disappearance (1/2 d) or biological half-life (t 1/2) was detected for either VIII procoagulant (VIII:C) or its antigenic counterpart VIII:C Ag. As anticipated there was a significant (if sub-optimal) increase in VIII:R Ag within 2-4 hours of D.D.A.V.P. administration.

Blood Transfusion↗

[Fatal hypoxemia following extracorporeal circulation for aortocoronary bypass. A case].

A lethal case of acute respiratory distress syndrome of the adult following extracorporeal circulation for aorto-coronary bypass is reported. This case illustrates the two mechanisms currently thought to be responsible for this pathology: (1) the passage of blood over the synthetic fibres of the cardiopulmonary bypass machine activates the complement, and the systemic inflammatory reaction that ensues accounts for the increased permeability of the alveolar capillary membrane; (2) the haemodilution inherent in extracorporeal circulation explains the hypoproteinaemia usually observed at the end of the procedure; the resulting fall in capillary osmotic pressure upsets the equilibrium of pressures in the capillary vessels.

Coronary Artery Bypass↗

Transient biochemical compartmentalization of Purkinje cells during early cerebellar development.

It has recently been observed that during early cerebellar development--from embryonic Day 17 to postnatal Day 3 in the rat--only certain discrete clusters of Purkinje cells (PCs) are immunoreactive to cyclic GMP-dependent protein kinase (cGK). In contrast, at later stages and in the adult, all the PCs are immunoreactive. These results obtained with cGK suggest a transitory intrinsic heterogeneity in the immature cerebellar cortex. It seemed therefore interesting to investigate the distribution of other PC markers during early development in the rat and in other species. The results presented here were obtained with two other antibodies--against vitamin D-dependent calcium binding protein and against Purkinje cell specific glycoprotein--which, like cGK, label all adult PCs. Each antibody gave a different and reproducible mosaic of positive and negative clusters of PCs in the perinatal cerebellum, thus indicating a transient biochemical compartmentalization resulting from the differential expression of parts of the same genotype by clusters of PCs. This compartmentalization in concomitant with the ingrowing of the cerebellar afferents. Once synaptogenesis starts, the biochemical heterogeneity of PCs disappears.

Animals↗

[Paraganglioma of the jugulo-tympanic glomus. Anatomo-pathological aspects].

15 extensive glomus jugulare tumors have been studied. Optic and ultrastructural data were very similar to those which have been reported in the literature. They possessed a local aggressiveness, demonstrated by progressive spreading in soft tissues and bone, intravascular digitations and destruction of cranial or sympathetic nerves. Dura-mater was usually preserved and prevented extension close to the brain stem. In this group, no functional activity of catecholamine-secreting tumor nor metastasis proving a malignant form were observed.

Diagnosis, Differential↗

[Papillary "endometrial" adenocarcinoma of the bladder neck. Light and electron microscopy and immunohistochemistry].

A case of papillary adenocarcinoma, developed on the urinary bladder neck is reported. This tumor is histologically identical to so called endometrial carcinoma of the prostate. Immunohistochemistry showed acid phosphatases and prostatic specific antigen (PSA) positive cells. Electron microscopy disclosed secretory vacuoles consistent with a prostatic origin. The histogenesis of endometrial carcinoma is briefly discussed likewise the precise site of origin of the reported case.

Acid Phosphatase↗

Continuous subcutaneous infusion of glucagon by portable pump in non beta cell tumor hypoglycemia.

Subcutaneous infusion of glucagon by portable pump appears to give very effective symptomatic relief from non beta cell tumor hypoglycemia when surgery, radiotherapy and chemotherapy are impossible or ineffective. This mode of glucagon administration was proposed in a patient who had severe nocturnal hypoglycemic attacks. The aim of the study was to specify the modes of utilization and to test the efficiency and the tolerance of this treatment. Glucagon was infused at 400 micrograms/h during every 12 hour night. Because of the hepatic action of glucagon it is very important to use this treatment with an adequate diet and to stop the infusion during the day to reconstitute the glycogen overload. This mode of glucagon administration was very effective in over 6 months of use and well tolerated.

Blood Glucose↗

Asynchrony in the expression of guanosine 3':5'-phosphate-dependent protein kinase by clusters of Purkinje cells during the perinatal development of rat cerebellum.

The early maturation of Purkinje cells was studied by immunocytochemistry in the rat cerebellum. The antiserum against guanosine 3':5'-phosphate-dependent protein kinase used in this study has been shown previously to label specifically all Purkinje cells in the adult rat. Immunoreactive Purkinje cells are first observed at embryonic day 17, 2 days after the end of proliferation of this neuronal population. At this time, most of the labeled cells are situated in the subventricular zone, although some immunoreactive Purkinje cells have already reached the cortex. Between embryonic day 17 and birth, four clusters of immunoreactive Purkinje cells appear in each hemicerebellum. Their time course and their pathways of migration to the cortex were followed. The immunoreactive clusters are tailed by a fibre-like immunostained material. The pattern of the migrating clusters at embryonic day 19 is very similar to the pattern of the corticonuclear projection observed at birth. From comparison between sections of embryos processed either for immunocytochemistry or Cresyl Violet staining, it appears that all the Purkinje cells are not immunoreactive. Positive and negative clusters of Purkinje cells are sharply delineated, their cells never mix. Immunopositive and negative clusters of Purkinje cells coexist until postnatal day 3. However, from birth onwards, negative clusters begin progressively in a caudorostral sequence to express guanosine 3':5'-phosphate-dependent protein kinase and rapidly attain the same level of immunoreactivity as previously labeled clusters. From postnatal day 5 all the Purkinje cells are immunoreactive. It is concluded that a compartmentalization of the cerebellar cortex is present very early and is evidenced by differences in the biochemical maturation of Purkinje cells. The axons of Purkinje cells reach the deep nuclei, following the same pathways as the clusters of Purkinje cells migrating to the cortex. Therefore, the mechanisms regulating the selection of the migratory routes followed by each Purkinje cell cluster are essential for the achievement of the topography of the corticonuclear projection. The level of protein kinase immunoreactivity cannot be taken as an index of the overall maturation of Purkinje cells, because it does not always coincide with the expression of other makers of biochemical and morphological differentiation of these neurons. During the early establishment of the cerebellar maps, an asynchrony in the expression of parts of the same genotype in the Purkinje cells may help in the establishment of ordered connections.

Animals↗

Clinical features of early haemarthroses in severely affected adolescent haemophiliacs.

Six hundred and ninety bleeds into the knees, ankles and elbows of severe haemophiliacs presenting for treatment within 3 h of the onset of symptoms have been studied with the aim of providing clinical information for the haemophiliac patient or his parent treating early bleeding episodes at home. Patients were resident at a boarding school and documentation and follow-up to complete resolution was possible. Stiffness was a presenting symptom in 61% of elbow bleeds, 49% of knee bleeds and 18% of ankle bleeds. Pain was a presenting feature in 79% of ankle bleeds, 55% of knee bleeds and 42% of elbow bleeds. Tenderness was a common feature of ankle bleeds (85%), less so in elbows (55%) and knees (69%). Swelling was a very common feature at all sites and the mean increases in girth of the knees, elbows and ankles were 1.42 cm, 0.88 cm, and 0.62 cm, respectively. All the knee and elbow bleeds and 85% of the ankle bleeds had demonstrable restriction of movement. There was a direct relationship between the degree of swelling, extent of movement restriction and time taken for complete restoration of function, the mean of which was 3.6 days for elbows, 2.5 for knees and 1.1 for ankles.

Adolescent↗

[Diagnostic problems of tuberculoid cervical adenitis. Apropos of 70 cases].

Pathologic criteria in tuberculoid adenitis enable differentiation between follicular adenitis with or without caseous necrosis and that involving suppurative necrosis. The absence of specific etiology is emphasized. Seventy cases of tuberculoid adenitis are analyzed. Of the 62 cases of adenitis labelled tuberculous, bacterial confirmation was obtained in only 22 (35%), suggesting probable diagnosis by excess for the remaining 40 cases. Related bacteriologic problems concern isolation of B.K. of the 3 cases classified as sarcoidosis, it was important to obtain data from broncho-alveolar lavage and serum conversion enzyme assay. Four patients with adenitis were diagnosed as having cat-scratch disease from positive specific intradermal reactions, the probable discovery of the responsible agent thus providing a bacteriologic diagnosis.

Adolescent↗

[Surgical treatment of Basedow's disease. I--Traditions and new methods in preparation for thyroidectomy: use of dexamethasone].

The combination of dexamethasone (2 mg every 6 hours) carbimazole (15 mg every 8 hours) and potassium iodide (XV drops every 8 hours) has been proposed in the preparation of 21 patients with hyperthyroid Graves' disease for surgery. The combination was administered for 6 days and the subtotal thyroidectomy was performed on day 7. All patients had normal serum Triiodothyronine levels after 4 days of such treatment. This combined drug therapy appears to be a rapid, sage and effective preparation for thyroid surgery in patients with Graves' disease and should replace conventional preparation with carbimazole and potassium iodide and beta-blocker preparation in all cases where there are no contra-indications to the use of corticosteroids.

Adult↗

[Surgical treatment of Basedow's disease. II--Evaluation of 36 subtotal thyroidectomies].

Results of subtotal thyroidectomy in 36 patients with Graves' disease emphasize the need for strict medical preparation, with the administration of corticoids more particularly, and the technical imperatives required during operation. Analysis of endocrine factors showed that euthyroidism was obtained in 76% of cases with a fairly stable state after 6 months. Hyperthyroidism was rare and developed before the end of the first year. Hypothyroidism, mainly biologic, was frequent during the immediate postoperative period but compensatory hypertrophy of remaining tissue was the usual outcome. It was persistent in 14% of cases, however, but easily compensated by substitutive therapy and a less severe complication than prolonged hyperthyroidism. Biologic hypocalcemia was also frequent but normal levels were reinstituted rapidly. Surgical treatment of Graves' disease is usually effective and rapidly performed, and is particularly indicated when socio-ethnic conditions make medical treatment difficult or impossible.

Adolescent↗

Cells with neuronal properties in permanent cultures of quail embryo neuroretinas infected with Rous sarcoma virus.

Neuroretina cells from 7-day quail embryos infected 'in vitro' with the mutant ts NY-68 of Rous sarcoma virus, were established into permanent cultures. An initial stage of cellular proliferation was followed by a period of minimal multiplication. After recovery from this crisis, cell proliferation resumed. About 30% of the cells had binding sites for tetanus toxin and the monoclonal antibody A2B5 which seem to be specific for neurons, and an ultrastructural study suggested the presence of neurons and Müller (astroglial) cells. The specific activity of glutamic acid decarboxylase, the enzyme responsible for the synthesis of the neurotransmitter gamma-aminobutyric acid was high (10-30 nmol CO2/h/mg of protein) and electrophysiology showed that some cells had 'active' membranes. After about 18 months in culture, approximately 20% of the cells were able to respond to electrical stimulation by producing action potentials which were inhibited by 10(-7) M tetrodotoxin. These electrophysiological properties are stable: they have been repeatedly found at regular intervals throughout a 20 months period. Furthermore, a clone in which all tested cells are excitable, has been derived from the mass culture. Quail embryo neuroretina cells with typical neuronal properties can thus be established into permanent cultures after infection with Rous sarcoma virus.

Action Potentials↗