Increased density of microtubule associated protein 2-immunoreactive neurons in the prefrontal white matter of schizophrenic subjects

Recent studies have suggested that schizophrenia may be related to prenatal disturbances in the cortical subplate, a transient but essential structure in the formation of cerebral cortical circuitry. Although most subplate neurons die during later development, some remain as the interstitial neurons of the adult white matter. In this study we used a monoclonal antibody against the cytoskeletal protein, microtubule associated protein-2 (MAP2), to quantify the density and distribution of labeled neurons in postmortem brain specimens containing the prefrontal white matter from five schizophrenic cases and matched controls. In both schizophrenics and matched controls, the density of white matter neurons decreased with increasing white matter depth. However, the mean density of MAP2-immunoreactive neurons was greater in the superficial white matter of the schizophrenic subjects compared to the matched controls. In contrast, no difference in the density of labeled neurons was seen in the deeper white matter. These findings are consistent with an abnormality in the development of the cortical subplate in at least some cases of schizophrenia.     

Characteristics of cation binding to the I domains of LFA-1 and MAC-1. The LFA-1 I domain contains a Ca2+-binding site

The crystal structures of the I domains of integrins MAC-1 (alphaM beta2; CD11b/CD18) and LFA-1 (alphaL beta2; CD11a/CD18) show that a single conserved cation-binding site is present in each protein. Purified recombinant I domains have intrinsic ligand binding activity, and in several systems this interaction has been demonstrated to be cation-dependent. It has been proposed that the I domain cation-binding site represents a general metal ion-dependent adhesion motif utilized for binding protein ligands. Here we show that the purified recombinant I domain of LFA-1 (alphaLI) binds cations, but with significantly different characteristics compared with the I domain of MAC-1 (alphaMI). Both alphaLI and alphaMI bind 54Mn2+ in a conformation-dependent manner, and in general, cations with charge and size characteristics similar to Mn2+ most effectively inhibit 54Mn2+ binding. Surprisingly, however, physiological levels of Ca2+ (1-2 mM) inhibited 54Mn2+ binding to purified alphaLI, but not to alphaMI. Using 45Ca2+ and 54Mn2+ in direct binding studies, the dissociation constants (KD) for the interactions between these cations and alphaLI were estimated to be 5-6 x 10(-5) and 1-2 x 10(-5) M, respectively. Together with the available structural information, the data suggest differential affinities for Mn2+ and Ca2+ binding to the single conserved site within alphaLI. Antagonism of LFA-1, but not MAC-1, -mediated cell adhesion by Ca2+ may be related to the Ca2+ binding activity of the LFA-1 I domain.     

Retinal ganglion cell axon progression from the optic chiasm to initiate optic tract development requires cell autonomous function of GAP-43

Pathfinding mechanisms underlying retinal ganglion cell (RGC) axon growth from the optic chiasm into the optic tract are unknown. Previous work has shown that mouse embryos deficient in GAP-43 have an enlarged optic chiasm within which RGC axons were reportedly stalled. Here we have found that the enlarged chiasm of GAP-43 null mouse embryos appears subsequent to a failure of the earliest RGC axons to progress laterally through the chiasm-tract transition zone to form the optic tract. Previous work has shown that ventral diencephalon CD44/stage-specific embryonic antigen (SSEA) neurons provide guidance information for RGC axons during chiasm formation. Here we found that in the chiasm-tract transition zone, axons of CD44/SSEA neurons precede RGC axons into the lateral diencephalic wall and like RGC axons also express GAP-43. However unlike RGC axons, CD44/SSEA axon trajectories are unaffected in GAP-43 null embryos, indicating that GAP-43-dependent guidance at this site is RGC axon specific or occurs only at specific developmental times. To determine whether the phenotype results from loss of GAP-43 in RGCs or in diencephalon components such as CD44/SSEA axons, wild-type, heterozygous, or homozygous GAP-43 null donor retinal tissues were grafted onto host diencephalons of all three genotypes, and graft axon growth into the optic tract region was assessed. Results show that optic tract development requires cell autonomous GAP-43 function in RGC axons and not in cellular elements of the ventral diencephalon or transition zone.     

Erwinia amylovora secretes DspE, a pathogenicity factor and functional AvrE homolog, through the Hrp (type III secretion) pathway

Erwinia amylovora was shown to secrete DspE, a pathogenicity factor of 198 kDa and a functional homolog of AvrE of Pseudomonas syringae pv. tomato. DspE was identified among the supernatant proteins isolated from cultures grown in an hrp gene-inducing minimal medium by immunodetection with a DspE-specific antiserum. Secretion required an intact Hrp pathway.     

On the protective mechanisms of nitric oxide in acute pancreatitis

Nucleosome dimers from chicken erythrocytes show an ionic strength dependence of sedimentation coefficient similar to that of trimers, and indicative of a degree of compaction over a range of low ionic strengths. This is not easily reconciled with straight linkers but is consistent with bending or kinking of the linker DNA.     

Neuropsychological outcomes in randomized controlled trials of antiepileptic drugs: a systematic review of methodology and reporting standards

PURPOSE: To systematically review the methodology and use of neuropsychological tests in randomized controlled trials (RCTs) of antiepileptic drugs (AEDs) in patients with epilepsy. METHODS: Trial reports were found by searching Medline 1966-1996 and searching through journals by hand. Inclusion and exclusion criteria were applied, and methodological and neuropsychological test data was extracted by using a proforma. RESULTS: 43 reports met our inclusion criteria, representing 40 RCTs. as three RCTs had generated two reports. Twenty-two were actively controlled, and 18 were placebo-controlled studies. Reporting of basic methods such as randomization method was poor. There has been no uniform approach to the use of neuropsychological tests, and a total of 87 has been used. The Stroop Colour Word Test and the Finger Tapping Test were most commonly used, at 13 times each, but were not used or reported in a uniform manner. CONCLUSIONS: Poor reporting of methods and the use of a plethora of neuropsychological tests create great difficulties for anyone wishing to make sense of currently available data. If we are better to understand the neuropsychological effects of AEDs, a more rational approach is needed, for which recommendations are made.     

Seven deaths in Darwin: case studies under the Rights of the Terminally Ill Act, Northern Territory, Australia

BACKGROUND: During the 9 months between July, 1996, and March, 1997, the provision of euthanasia for the terminally ill was legal in the Northern Territory of Australia. Seven patients made formal use of the Rights of the Terminally Ill (ROTI) Act; four died under the Act. We report their clinical details and the decision-making process required by the Act. METHODS: We taped in-depth interviews with the general practitioner who provided euthanasia. Further information was available from public texts created by patients, the media, and the coroner. FINDINGS: All seven patients had cancer, most at advanced stages. Three were socially isolated. Symptoms of depression were common. Having met criteria of the Act, some patients deferred their decision for a time before proceeding with euthanasia. Medical opinions about the terminal nature of illness differed. INTERPRETATION: Provision of opinions about the terminal nature of illness and the mental health of the patient, as required by the ROTI Act, created problematic gatekeeping roles for the doctors involved.     

In vitro 2,3,7,8-tetrachlorodibenzo-p-dioxin interference with the anterior pituitary hormone adrenocorticortropin

Pharmacological effects of acute treatment with venlafaxine (VEN), a clinically active antidepressant [a noradrenaline (NA) and 5-hydroxytryptamine (5-HT) reuptake inhibitor without any affinity for neurotransmitter receptors] were studied in mice and rats. VEN inhibited the reserpine- or apomorphine-induced hypothermia and enhanced the L-5-HTP-induced head twitches in mice. It reduced the immobility time in Porsolt's test in mice and rats, but either did not change the locomotor activity (mice) or decreased it (rats). VEN reduced the locomotor hyperactivity induced by amphetamine (AMP), apomorphine (APO) and quinpirole (QUI), as well as the APO-induced stereotypy; the stereotypy induced by AMP in rats was prolonged. VEN neither changed the clonidine-induced aggressiveness in mice nor the behavioral syndrome induced by oxotremorine in rats. The obtained results indicate that VEN, given acutely, shows a pharmacological profile similar to that of tricyclic NA and 5-HT reuptake inhibitors. In contrast to the antidepressants mentioned above, VEN does not exhibit an alpha 1-adrenolytic or a cholinolytic activity (in vivo tests).