The significance of extracellular GABA in the substantia nigra of the rat during seizures and anticonvulsant treatments

The effects of the anti-epileptic drugs valproic acid and gamma-vinyl-GABA j(vigabatrin) on the extracellular content of GABA was determined by microdialysis. Probes were implanted in the substantia nigra reticulata (SNR) of rats. It was found that gamma-vinyl-GABA (1000 mg/kg) induced a 4–6-fold increase in the extracellular content of GABA. This increase lasted for at least 72 h. PTZ-induced convulsions were partly antagonized by the GVG treatment. The increase of extracellular GABA after gamma-vinyl-GABA was not affected by infusion of tetrodotoxin. In contrast valproic acid (200 mg/kg), although effective in preventing pentylenetetrazol (PTZ)-induced convulsions, did not affect extracellular GABA in the SNR. PTZ-induced convulsions did not modify extracellular GABA, neither in control rats nor in valproic acid or gamma-vinyl-GABA pretreated animals. The results do not support the idea that extracellular GABA in the SNR plays a significant role in anti-convulsive treatment. However, the present data can also be interpreted that extracellular GABA, as sampled by microdialysis, is not a reliable marker for GABA release.     

Retinopathy of prematurity

Over the last decade major advances have been made in the understanding of the pathogenesis and evolution of retinopathy of prematurity (ROP). The increased survival of very small premature infants in modern neonatal intensive care units has led to the resurgence of this potentially blinding disease. ROP appears to be a multifactorial disease, the prevention of which is probably impossible even now, with the most accurate methods of blood gas monitoring and oxygen restriction. In addition to oxygen, there are a number of significant risk factors, such as birth weight and gestational age, ventilator hours, hyper and hypocarbia, hypoxia and acidosis, xanthine therapy and probably bright light. Current data suggest that the level of antioxidants in the immature retina is relatively low and therefore oxygen radicals which accumulate in the preterm baby's retina may play an important role in the pathogenesis of ROP. The treatment of the disease in both its "active" and "cicatricial" stages emphasizes the need for a new classification which could serve as a common international language through which results may be compared. Vitamin E was suggested in some studies to be helpful in preventing the severe stages of the disease, but its efficacy has yet to be proved. Treatment modalities such as photocoagulation, cryotherapy and vitrectomy are being tried as a means of therapy in the more advanced stages of the disease. Preliminary results of a large multicenter study support the efficacy of cryotherapy.     

Primary Health Care through a community based smoking-cessation program

The International Conference on Primary Health Care, meeting in Alma-Ata, in the Soviet Union, September 12, 1978, expressed the need for urgent action by all governments, all health and development workers and the world community, to protect and promote the health of all people of the world. The world was caught by the phrase which emerged from this conference, Health For All by the Year 2000 and many have examined the articles of the Alma-Ata declaration and tried to implement them in their corner of the world. This paper describes a community-based smoking-cessation program which was implemented in the province of Nova Scotia, Canada, during the years 1980–1984. Primary to this project was the belief that people have the right and the duty to participate individually and collectively in planning and implementing their health care. This paper describes one community's effort in putting this belief into practice.Carol Smillie, B.N. BE.d. M.S.c. is an Assistant Professor at the School of Nursing, Dalhousie University, Halifax, Nova Scotia, Canada B3H 3J5, Katherine Coffin, BA, MEd is the Program Officer, Nova Scotia Office, Health Promotion Directorate Health and Welfare Canada, 5251 Duke Street, Halifax, Nova Scotia. Canada B3J 1P3. Kathryn Porter, B.A. (Gen)., is the Information and Education Coordinator, Nova Scotia Division Canadian Cancer Society. Brenda Ryan, B.A., M.B.A. is Program Evaluation Analysist, Nova Scotia Department of Health, 6088 Hollis Street, Halifax. Nova Scotia, Canada. This Project was funded by Health and Welfare Canada, Nova Scotia Department of Health, Nova Scotia Division Canadian Cancer Society, Requests for reprints should be addressed to: Professor Carol Smillie.     

A microwave technique for double indirect immunostaining of human brain tissue cultures with mouse monoclonal antibodies.

The use of 2 monoclonal antibodies during double immunohistochemistry would enable the use of a greater variety of antibody combinations. Here, we demonstrate a simple, cost effective method of double indirect immunostaining of cultured cells using primary antibodies from the same species. This method uses microwaving of cell samples immediately after the application of the first secondary antibody, and significantly reduces the level of nonspecific staining. This technique does not elute the antibodies, nor raise the sample temperature above 37 degrees C.     

Kallikrein 4 expression is up-regulated in epithelial ovarian carcinoma cells in effusions

We immunohistochemically analyzed kallikrein 4 protein (hK4) expression in patients with epithelial ovarian carcinoma (181 malignant effusions and 103 solid carcinoma lesions). Expression of hK4 was also studied in 32 effusions using immunoblotting. Carcinoma cells expressed hK4 in 144 (79.6%) of 181 effusions and 85 (82.5%) of 103 solid tumors. Expression was seen in 51% or more of tumor cells in 70 effusions but often was limited to 5% or fewer cells in solid tumors (P = .009, primary tumors vs effusions; P = .002, metastases vs effusions). Immunoblotting showed hK4 expression in 31 of 32 specimens. Stromal cell hK4 expression, seen in 48 (46.6%) of 103 lesions, was significantly higher in primary tumors than metastases (26/43 vs 22/60, P = .019). hK4 expression in tumor cells was significantly lower in International Federation of Gynecology and Obstetrics stage IV than stage III tumors (P = .004, all lesions; P = .012, primary tumors). hK4 expression in carcinoma cells was associated with longer overall survival (not significant; P = .14, peritoneal effusions). hK4 is expressed widely in ovarian carcinoma; levels in carcinoma cells are highest in effusions, which might be related to loss of stromal contribution and/or altered microenvironment. hK4 expression in carcinoma cells of effusions or solid tumors does not predict survival.     

Lymphoepithelioma-like carcinoma of the bladder: three cases with clinicopathological and p53 protein expression study

Lymphoepithelioma-like carcinoma of the bladder is an uncommon neoplasm, of which 49 cases have been described in the English literature, none of which has been studied for p53 protein expression. We studied three muscle-infiltrating cases of this tumor using immunohistochemical, in situ hybridization and polymerase chain reaction (PCR) methods. The three cases were positive for epithelial markers and negative for lymphoid antigens in the tumoral syncytial areas. The intensive infiltrate of small cells was negative for epithelial and positive for lymphoid markers. This population was mainly made up of cytotoxic T-lymphocytes, positive for TIA-1. p53 protein was intensely positive in more than 90% of the epithelial component nuclei, being negative in the lymphoid cells. PCR study did not show mutations on p53. Both lymphocytes and epithelium were negative for Epstein–Barr virus markers, such as the latent membrane protein and EBER (Epstein–Barr-encoded RNA). The prognosis was very good after radiotherapy and chemotherapy treatment, preserving the bladder despite the muscle infiltration. The presence of an intense cytotoxic T-lymphocyte population may be related to this good prognosis. Both aspects, p53 protein status and T-lymphoid population, had never been studied before in bladder lymphoepithelioma-like carcinoma.     

Cell cycle synchronisation by 3-hydroxypyridin-4-one iron chelators

We describe a protocol for the synchronisation of normal and tumour cells grown in suspension cultures using 3-hydroxypyridin-4-one iron chelators. These compounds inhibit ribonucleotide reductase, one of the rate limiting enzymes in DNA synthesis, and so block the cell cycle in late G₁ phase. After removal of the chelator or repletion of cellular iron, cells progress through the cycle and remain synchronised for at least one full cell cycle. Cell viability is unaffected for at least 72 hours post-incubation and chelator treatment has no effect on RNA and protein synthesis. This method of synchronisation has been successful with all cell lines tested including normal and leukaemic human cell lines.     

A fractal analysis of pyramidal neurons in mammalian motor cortex.

Pyramidal neurons in the mammalian cerebral cortex can be described by a fractal dimension (Mandelbrot, 1982), which is an objective, quantitative measure of the complexity of their soma/dendritic borders. In the cat, the fractal dimensions of lamina V cells, which include pyramidal tract neurons (PTN), indicate that these cells are more complex than other pyramidal neurons (PN) in the same region of motor cortex. The lamina V cells of the cat are also more complex than those in motor cortex of the monkey. Moreover, lamina III neurons in the monkey are more complex than monkey lamina V neurons. The fractal dimension of the intracortical axon collateral arborizations of the same pyramidal neurons indicated, in all cases, that the branching of these terminals is less complex than the branching of the dendrites of the same cells. In line with the observation that the fractal dimensions of some homologous cellular populations are different in different species, it is suggested that the fractal dimension and the degree of morphological complexity may relate to the requirement for the number of separable functions to be accommodated within one neuron. For example, as the size of the cortex and the number of neurons in a region increase, the opportunity exists within a given cortical zone, for individual functions to be segregated and for functional specialization to be accommodated with less morphological complexity of the individual neurons performing each of these functions.     

Marden-Walker syndrome: case report, literature review and nosologic discussion

Schrander-Stumpel C, de Die-Smulders C, de Krom M, Schyns-Fleuren S, Hamel B, Jaeken D, Fryns J-P. Marden-Walker syndrome: case report, literature review and nosologic discussion.
Clin Genet 1993: 43: 303–308. © Munksgaard, 1993
The Marden-Walker syndrome is characterized by psychomotor retardation, a mask-like face with blepharophimosis, micrognathia and a high-arched or cleft palate, low-set ears, kyphoscoliosis and joint contractures. We report on a male patient with the clinical features of the syndrome. In addition, he had a Dandy-Walker malformation with hydrocephalus and vertebral abnormalities. During pregnancy, there were feeble fetal movements and polyhydramnios. We propose that Marden-Walker syndrome is one of the etiologic possibilities in children with the heterogeneous fetal a(hypo)kinesia deformation sequence (FADS). Differential diagnosis is discussed. The etiology is probably heterogeneous.