Species differences in the projections from the entorhinal cortex to the hippocampus

Both differences and similarities exist between mammalian species in the projections from entorhinal cortex to the hippocampal formation. In most species, layer II cells of the entorhinal cortex project to the dentate gyrus, and they terminate in the outer two-thirds of the molecular layer of the dentate gyrus. The axons from layer III cells project bilaterally to areas CA(1) and CA(3) of the hippocampus, terminating in the stratum lacunosum moleculare. We have analyzed these projections in mice, and in general, the entorhinal cortex-to-hippocampus projections are similar to those in rats. Axons from layer II neurons terminate in the outer and middle thirds of the molecular layer of the dentate gyrus, and axons from layer III neurons terminate bilaterally in the stratum lacunosum moleculare of areas CA(1) and CA(3), and in the molecular layer of the subiculum. However, in contrast to rat, mouse entorhinal cortex neurons do not appreciably project to the contralateral dentate gyrus. Most species, including mice, show a similar topographical organization of the entorhinal-hippocampal projections, with neurons in the lateral part of both the lateral and medial entorhinal cortex projecting to the dorsal part or septal pole of the hippocampus, whereas the projection to the ventral hippocampus originates primarily from neurons in medial parts of the entorhinal cortex.     

Transgenic mice expressing the human presenilin 1 gene demonstrate enhanced hippocampal reorganization following entorhinal cortex lesions

We have examined the effects of the presence of the mutated human presenilin 1 gene (M146L; hps1*) on lesion-induced sprouting in the hippocampus of the mouse (C57/CBA). The entorhinal cortex was unilaterally lesioned with ibotenic acid in adult, male mice. Four weeks later the subsequent axonal sprouting in the dentate gyrus was analysed, by measuring the density of the synaptophysin immunocytochemical staining in the termination area of the entorhinal cortex axons. The data demonstrate that mice expressing either the human presenilin 1 gene (hps1) or the hps1* gene display a significantly increased density of immunocytochemical staining for synaptophysin, indicative of axonal sprouting, compared to the control mice. No (or a very small) sprouting response is observed in mice expressing the normal mouse ps1 gene. Taken together, these data indicate that the presence of a human ps1 gene, normal or with an Alzheimer's disease mutation, leads to enhanced plasticity in the mouse brain.     

Alcohol use,cigarette consumption and chronic post-traumatic stress disorder

AIMS: The relationship between alcohol consumption, cigarette smoking and post-traumatic stress disorder (PTSD) was studied in 147 male former members of the civilian resistance against the Nazi occupation of Holland during World War II. METHODS: The subjects were interviewed at home. Measures included rating of current PTSD and a self-report measure of smoking and alcohol use. RESULTS: The weekly alcohol consumption reported by veterans was substantially below that of the general population. Furthermore, there was no significant difference in self-reported alcohol consumption between veterans with and without current PTSD. Cigarette smoking, however, was more prevalent in those with current PTSD. CONCLUSIONS: The absence in these veterans of a correlation between PTSD and alcohol consumption is contrary to the results of most studies on this subject. It may be related to the exclusion from organized resistance activities of people prone to the over-consumption of alcohol. It is hypothesized that, in trauma survivors, current substance use is associated with peri-traumatic patterns of psychological tension-reduction modes.     

The role of the laterodorsal nucleus of the thalamus in spatial learning and memory in the rat

The anterior thalamic nuclei appear to play an important role in learning and memory. Connectionally and structurally, the lateral dorsal nucleus is similar to the anterior nuclei. This study tested the hypothesis that the laterodorsal thalamic nucleus (LD) also contributes to these functions. Adult Sprague-Dawley rats received bilateral ibotenic acid lesions of LD, and 2 weeks later the rats were tested in a repeated acquisition water maze task. The control groups displayed a short final escape latency and showed a preference for the correct quadrant in the probe trial. Rats with a lesion restricted to LD (LDL) were mildly impaired in the task, but rats with lesions that destroyed LD and also significantly (50%) damaged the adjacent anterior thalamic nuclei (LDL+) were severely impaired, displaying no improvement in performing the spatial task. In a second experiment, training in the same paradigm for 2 weeks resulted in improved final performance by LDL and control rats but not by LDL+ rats. These findings support the hypothesis that together with the anterior thalamic nuclei, LD plays a role in spatial learning and memory.     

Use of the NESS handmaster to restore handfunction in tetraplegia: clinical experiences in ten patients

OBJECTIVE: To explore possible functional effects of the Handmaster in tetraplegia and to determine suitable patients for the system. PATIENTS: Patients with a cervical spinal cord injury between C4 and C6, motor group 0 - 3. Important selection criteria were a stable clinical situation and the absence of other medical problems and complications. DESIGN: Ten patients were consecutively selected from the in- and outpatient department of a large rehabilitation hospital in The Netherlands. Each patient was fitted with a Handmaster by a qualified therapist and underwent muscle strength and functional training for at least 2 months. METHODS: Functional evaluation comprised the performance of a defined set of tasks and at least one additional task as selected by patients themselves. Tasks were performed both with and without the Handmaster. Finally, patients were asked for their opinion on Handmaster use as well as their willingness to future use. RESULTS: In six patients a stimulated grasp and release with either one or both grasp modes (key- and palmar pinch) of the Handmaster was possible. Four patients could perform the set of tasks using the Handmaster, while they were not able to do so without the Handmaster. Eventually, one patient continued using the Handmaster during ADL at home. CONCLUSION: The Handmaster has a functional benefit in a limited group of patients with a C5 SCI motor group 0 and 1. Suitable patients should have sufficient shoulder and biceps function combined with absent or weak wrist extensors. Though functional use was the main reason for using the Handmaster, this case series showed that therapeutic use can also be considered.     

Detection of diverse variants of human immunodeficiency virus-1 groups M, N, and O and simian immunodeficiency viruses from chimpanzees by using generic pol and env primer pairs

Human immunodeficiency virus type 1 (HIV-1) infection of humans is the result of independent cross-species transmissions of simian immunodeficiency viruses (SIVcpz) from naturally infected chimpanzees (Pan troglodytes troglodytes) to man. To develop a polymerase chain reaction-based assay capable of detecting members of all major phylogenetic SIVcpz and HIV-1 lineages (groups M, N, and O), primer pairs in conserved pol and env regions were designed. Both primer sets amplified 99%) in amplifying viral sequences from plasma taken from patients infected with HIV-1 group M (n=226) and O (n=17) viruses.     

Physiological anticoagulants and activated protein C resistance in childhood stroke

Immunological and functional protein S, protein C and antithrombin III levels and anticoagulant responses to activated protein C were measured in 24 patients with stroke in childhood. No hereditary deficiencies were found. The protein S levels in healthy controls of younger age did not differ from the adult levels. For optimal screening of protein S deficiency, measurements using functional as well as immunological assays are recommended. Appropriate criteria for the diagnosis of the deficiencies must be carefully applied if unnecessary anxiety and inappropriate treatment of children are to be avoided.     

Activity of high-dose epirubicin combined with gemcitabine in advanced non-small-cell lung cancer: a multicenter phase I and II study

The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21 -day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m(-2) on day 1 and gemcitabine 1125 mg m(-2) on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26-75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35-63%). The median survival time for the patients was 42 weeks (95% CI 13-69).