Prenatal Development of Parvalbumin Immunoreactivity in the Human Striate Cortex

In human primary visual cortex, parvalbumin (PV) is expressedby Cajal-Retzius cells in layer I by 20 weeks of gestation (20W),but its immunoreactivity is mostly lost by term. PV immunoreactivityin layers II–VI mainly develops later, from 26 to 34W,following an approximately ‘inside-outside’ sequencein a series of bands. PV-positive perikarya appear in layerV by 20W, but only in small numbers. They increase in numberand staining intensity by 26W. By 30W a band of densely labelledsomata and neuropil occupies layers IVC–VI. By 34W a second,less dense, band of cell bodies and neuropil appears in IVBand IVC     

Evaluating the Effects of Surotomycin Treatment on Clostridium difficile Toxin A and B Production,Immune Response,and Morphological Changes

Surotomycin is a cyclic lipopeptide in development for Clostridium difficile-associated diarrhea. This study aimed to assess the impact of surotomycin exposure on C. difficile toxin A and B concentrations and the associated changes in immune response in comparison to vancomycin and metronidazole. Time-kill curve assays were performed using strain {"type":"entrez-nucleotide","attrs":{"text":"R20291","term_id":"774925","term_text":"R20291"}}R20291 (BI/NAP1/027) at supra-MICs (4× and 40×) and sub-MICs (0.5×) of surotomycin and comparators. Following treatment, CFU counts, toxin A and B concentrations, and cellular morphological changes using scanning electron microscopy were examined. Inflammatory response was determined by measuring interleukin-8 (IL-8) concentrations from polarized Caco-2 cells exposed to antibiotic-treated C. difficile growth media. Supra-MICs (4× and 40×) of surotomycin resulted in a reduction of vegetative cells over 72 h (4-log difference, P < 0.01) compared to controls. These results correlated with decreases of 77% and 68% in toxin A and B production at 48 h, respectively (P < 0.005, each), which resulted in a significant reduction in IL-8 concentration compared to controls. Similar results were observed with comparator antibiotics. Bacterial cell morphology showed that the cell wall was broken apart by surotomycin treatment at supra-MICs while sub-MIC studies showed a “deflated” phenotype plus a rippling effect. These results suggest that surotomycin has potent killing effects on C. difficile that results in reduced toxin production and attenuates the immune response similar to comparator antibiotics. The morphological data also confirm observations that surotomycin is a membrane-active antibiotic.     

Management of rash and other toxicities in patients treated with epidermal growth factor receptor-targeted agents

Inhibition of the epidermal growth factor receptor (EGFR) represents one of the most important avenues for research and development in the field of cancer therapy. The EGFR is a member of the ErbB receptor tyrosine kinase (TK) family, which also includes ErbB-2 (HER2/neu), ErbB-3 (HER3), and ErbB-4 (HER4). Current EGFR therapies available for use include monoclonal antibodies, such as cetuximab, and small-molecule EGFR TK inhibition by agents such as erlotinib. Side effects of these agents include dermatologic manifestations without the bone marrow suppressive properties of chemotherapy. Understanding of rash and how it relates to EGFR inhibitor toxicity and, perhaps more importantly, EGFR inhibitor response must be more clearly defined with clinical trials. The optimum management of rash in patients receiving anti-EGFR therapy remains somewhat controversial; this is secondary to imprecise classification of rash as well as the lack of clinical trials to determine the most appropriate treatment algorithm for these patients. We propose a treatment strategy to help aggressively treat dermatologic side effects allowing patients to continue receiving therapy without dose interruption or drug discontinuation.     

Differential localisation of the metabotropic glutamate receptor mGluR1a and the ionotropic glutamate receptor GluR2/3 in neurons of the human cerebral cortex

Specimens of human cerebral cortex were obtained during neurosurgical operations and studied by immunocytochemistry and electron microscopy, using antibodies to the metabotropic glutamate receptor subunit mGluR1a and the ionotropic glutamate receptor GluR2/3. A small number of non-pyramidal neuronal cell bodies were labelled for mGluR1a. Double immunolabelling with mGluR1a and GluR2/3 showed that most pyramidal cell bodies were labelled for GluR2/3 but not for mGluR1a. Despite the non-colocalisation of these two receptor subtypes in cell bodies, however, many dendrites and dendritic spines were double-labelled for mGluR1a and GluR2/3 at electron microscopy. As there is evidence that most neurons positive for GluR2/3 are pyramidal cells, this suggests that mGluR1a is present in dendrites of pyramidal neurons, despite absent or low levels of immunoreactivity in their cell bodies. Received: 5 May 1997 / Accepted: 24 July 1997     

Morphology of the neurons in the human lateral geniculate nucleus and their normal development

Summary Neurons in the adult human lateral geniculate nucleus have been classified using Golgi preparations. The neuronal classes correspond to those previously described in monkey (Saini and Garey 1981). The commonest are multipolar neurons with either radiate or tufted dendritic trees. Also seen frequently are bipolar neurons with two or three diametrically opposed dendrites. Rarer classes include neurons with beaded dendrites and those with axon-like dendritic processes, perhaps inter-neurons. Neurons are also found in the circumgenicule capsule. Most neurons have dendrites restricted to the laminae, but some dendrites cross the borders of both magno- and parvocellular laminae. Somata are also seen in interlaminar zones with dendrites reaching the adjacent laminae. No significant difference, apart from size, is found between neurons in magno- and parvocellular laminae.Most neuronal types are found at birth. They are, however, strikingly different from their adult forms in having growth cones and filopodia and an abundance of dendritic and somatic spines and hair-like processes. Morphological maturity is reached by about nine months postnatally. Similar maturational changes occur in monkey in the first two months of life (Garey and Saini 1981) and in both monkey and man this period of maturation of the lateral geniculate nucleus corresponds to increasing visual acuity and a time when each species is most likely to be affected by visual deprivation.Supported by the Swiss National Science Foundation (3.612.80)The work described in this paper forms part of a study for a doctoral dissertation in the University of Lausanne by C. de Courten     

Morphology of neurons in the lateral geniculate nucleus of the monkey

Summary Rapid Golgi preparations of the lateral geniculate nucleus of old- and new-world monkeys were analysed in an attempt to classify the neuronal types. Four main types are described. The commonest, the multipolar neurons, are found in all laminae. Their somata can be large, medium or small and bear dendrites with sparse spines. Some have a radiate dendritic arbor and others have dendrites grouped in tufts. The next most frequent class is of bipolar neurons with two thick dendrites arising from opposite poles of the soma, which is usually large. Otherwise the dendrites are similar to those of multipolar neurons. Relatively rare is a class of medium-sized neurons with beaded dendrites, found here only in magnocellular laminae. There is a fourth class of small neurons distinguished by fine axonlike dendritic processes. They are in all laminae and form two subgroups, one with very long, cylindrical dendrites and few axon-like processes, the other with shorter dendritic arbors and many axon-like processes. In addition, a class of capsular neurons is found in the circumgeniculate capsule between layer 6 and the pregeniculate nucleus. They are large neurons with umbrella-like dendritic arbors sending ramifications into layer 6. The interlaminar zones contain scattered somata of all types except beaded and capsular neurons.The work described in this paper forms part of a study for a doctoral dissertation in the University of Lausanne by K.D. Saini