Central actions of somatostatin

Somatostatin (SRIF) was applied microiontophoretically to neurons in the frontal and parietal neocortex, the hippocampus and the striatum of rats anaesthetized with either urethane or chloral hydrate. Qualitatively identical results were obtained under both anaesthetic conditions. In urethane-treated rats SRIF elicited a dose-dependent increase of the firing rate of 74% of the neurons studied in the frontal cortex and of 46% of the neurons studied in the parietal cortex. All cortical cells identified as pyramidal cells were excited. In the hippocampus SRIF provoked excitatory responses in two thirds of all neurons. Six out of the nine cells identified as pyramidal cells were excited by SRIF. In the striatum 80% of all neurons were excited. Following repeated exposure of central neurons to SRIF, the magnitude of the excitatory response gradually diminished, indicating desensitisation. SRIF in concentrations ranging from 10(-8) to 10(-4) M did not interfere with the binding of (3H)-muscimol to GABA receptor sites. The release of GABA from synapses preloaded with (3H-GABA) was not influenced by SRIF in the concentration range from 10(-6) to 10(-4) M. These results indicated that SRIF does not evoke the excitatory responses through attenuation of GABA-mediated inhibition. In conclusion, the findings support the hypothesis that somatostatin may function as a neurotransmitter in the central nervous system.     

Glutamate transport in cultures from developing avian cerebellum: Presence of GLT-1 immunoreactivity in Purkinje neurons

Immunocytochemical studies indicated that Purkinje cells cultured from chick embryonic cerebellum (embryonic day 8) strongly express a glutamate transporter EAAT2 cloned from human brain (GLT-1 in rat brain). At both 7 days and 14 days in culture, Purkinje neurons accumulated 1 μM [³H]L -glutamate via a potent “high-affinity” transport system that could be inhibited by D - and L -threo-3-hydroxyaspartate (D - and L -t-3OHA) and by L-trans-pyrrolidine-2,4-dicarboxylate (L -t-PDC). The order of potency of the three inhibitors was L -t-PDC ∼ L -t-3OHA > D -t-3OHA. Only the value of IC₅₀ (concentration causing 50% inhibition) for D -t-3OHA significantly changed between 7 days (116 μM) and 14 days in culture (40 μM). All n_H ∼ 1, except in the case of the inhibition by D -t-3OHA at 14 days in culture (n_H = 0.57), indicating the possible appearance of heterogeneity of the transport sites at later stages of culturing. Chronic inhibition of L -glutamate transport by L -t-PDC resulted in major changes in the morphology of Purkinje cells; particularly, the neurites almost completely regressed. J. Neurosci. Res. 54:595–603, 1998. © 1998 Wiley-Liss, Inc.     

Detection of circulating crosslinked fibrin derivatives by a heat extraction-SDS gradient gel electrophoretic technique

A technique has been developed to identify and quantitate unique plasmic degradation products of crosslinked fibrin in plasma. In this method, fibrin derivatives are extracted by heat precipitation and dissolved with disulfide bond reduction, after which the crosslinked gamma-gamma chain remnants are identified by SDS-polyacrylamide gradient gel electrophoresis and quantitated by densitometric analysis. A heterogenous group of gamma-gamma chains with molecular weights between 100,000 and 76,000 daltons was identified in lysates of crosslinked fibrin during plasmic degradation in vitro. Three stages of crosslinked fibrin degradation have been arbitrarily defined based primarily on the extent of degradation of these gamma-gamma polypeptide chains. As little as 20 microgram of crosslinked fibrin digests added to 1 ml of normal plasma could be detected by the heat-extraction--gel- electrophoresis technique, identifying the gamma-gamma derivatives with molecular weights of 96,000, 86,000, 82,000, and 76,000 daltons. Plasmic derivatives of gamma-gamma chains were not found in normal plasma, but they were identified in the plasma of patients with disseminated intravascular coagulation and deep-vein thrombosis, both before and in increased quantity during successful thrombolytic therapy.     

WNT10A variants: following the pattern of inheritance in tooth agenesis and self-reported family history of cancer

Clinical Oral Investigations - The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of...     

Multiphasic MR imaging: a new method for direct imaging of pulsatile CSF flow

A new technique is described that allows for the creation of pure pulsatile flow magnetic resonance (MR) images in a single acquisition. Five to 16 electrocardiographically gated images spanning the entire cardiac cycle are obtained with use of a gradient-echo pulse sequence. The section can be varied from 4 mm thick to full thickness projection. Taken singly, each image provides direct assessment of flow direction and velocity. Subtraction of image pairs eliminates signal detected from stationary protons, producing images of pulsatile flow. In this study the technique was used to image the flow of cerebrospinal fluid (CSF) in healthy subjects and in one patient with syringohydromyelia. The data suggest that multiphasic MR imaging provides a powerful means for the noninvasive assessment of CSF pulsatile flow dynamics and may have potential clinical application for the investigation of a variety of abnormalities such as normal pressure hydrocephalus, syrinx, and spinal block.     

Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression

Microvascular thrombi underlie many of the clinical manifestations of Rocky Mountain spotted fever (RMSF), a disease characterized by Rickettsia rickettsii infection of vascular endothelial cells. Studies were designed to determine whether R rickettsii-infection of cultured human umbilical vein endothelial cells results in tissue factor (TF) induction, a process that could directly activate coagulation in infected vessels. Whereas uninfected endothelial cell cultures showed essentially undetectable TF mRNA and activity, both TF mRNA and activity were present after R rickettsii infection. TF mRNA levels were transient, peaking at 4 hours after the initiation of infection, whereas the peak of TF activity occurred at 8 hours. Induction of the TF response requires the intracellular presence of R rickettsii organisms, because uninfected rickettsia were ineffective and the response was blocked by inhibiting rickettsial entry using cytochalasin B. TF induction was not mediated by endothelial cell release of soluble factor, because no response was induced using culture medium conditioned by R rickettsii-infected cells. Furthermore, preadsorption of suspensions of R rickettsii with polymyxin B to remove contaminating lipopolysaccharide did not eliminate the TF response. Induction of TF in vital endothelial cells during R rickettsii infection could be the trigger for vascular thrombus formation of RMSF.     

MR gated subtraction angiography: evaluation of lower extremities

We report the first clinical experience with a new method for projective imaging of blood vessels (angiography) using magnetic resonance. Vascular contrast is produced noninvasively by the phase response of moving protons. Diastolic and systolic gated images produce, respectively, flow signal and flow void; the difference image is a map of the pulsatile flow: an arteriogram. Preliminary studies are presented of the lower extremities of one healthy volunteer and four patients (one each with occlusive disease, soft-tissue tumor, arteriovenous malformation, and venous femoral-popliteal graft). Patient data are compared with accompanying conventional arteriograms, and the new method is discussed.     

Indications for breast imaging in women under age 35 years

To determine appropriate indications for breast imaging in young women, the authors correlated patient histories with mammographic and/or sonographic findings and biopsy or follow-up results for 625 patients aged 13-34 years. The only important indications were a palpable mass and suspicion of an abscess. Of the 335 studies performed for evaluation of a palpable mass, 184 (55%) were normal, 28 (8%) were compatible with benign disease, and 123 (37%) were suggestive of malignancy. Biopsies were performed in 73 patients; the findings were benign in 67 cases, and carcinoma was found in six. Imaging studies were considered helpful in four of the 15 cases of suspected abscess, in that the studies established the presence and extent of an abscess. Studies in 275 women were performed for a variety of other indications. The findings were normal in 239 (87%) studies, benign in 21 (8%), and suggestive of malignancy in 15 (5%); there were no known carcinomas in any of the patients. Women with the "low-yield" indications identified in this study should be followed up clinically rather than referred for imaging studies.