APOE2 allele increased in tardive dyskinesia.

Ninety-seven inpatients with tardive dyskinesia (average AIMS score = 13), the majority of whom were schizophrenic, were studied. Forty patients were Caucasian, and 57 were African-American. The APOE genotypes of these patients were compared to previously published genotypes of controls and with previously published studies of APOE genotypes in patients with schizophrenia. There were no significant differences in APOE allele frequencies comparing the African-American tardive dyskinesia population and the African-American control groups. In contrast, significant (< 0.05) P values were obtained comparing the Caucasian tardive dyskinesia population to the Caucasian controls, when comparing allele frequencies and genotypic frequencies. This study suggests that Caucasians bearing an APOE2 allele are at increased risk of developing tardive dyskinesia, whereas African-Americans are not. APOE genotype-specific risks of both tardive dyskinesia and Alzheimer's disease that vary across populations could be due to recruitment of patients or controls or could be due to modifying effects of differing genetic or environmental backgrounds. The mechanism by which the APOE2 allele increases risk of tardive dyskinesia is not known. Further information about the mechanisms of increased risk of tardive dyskinesia could result in stratification of prescribing practices weighing the costs of medications against the relative risk of side effects.     

Cognitive Computation with Autonomously Active Neural Networks: An Emerging Field

The human brain is autonomously active. To understand the functional role of this self-sustained neural activity, and its interplay with the sensory data input stream, is an important question in cognitive system research and we review here the present state of theoretical modeling. This review will start with a brief overview of the experimental efforts, together with a discussion of transient versus self-sustained neural activity in the framework of reservoir computing. The main emphasis will be then on two paradigmal neural network architectures showing continuously ongoing transient-state dynamics: saddle point networks and networks of attractor relics. Self-active neural networks are confronted with two seemingly contrasting demands: a stable internal dynamical state and sensitivity to incoming stimuli. We show, that this dilemma can be solved by networks of attractor relics based on competitive neural dynamics, where the attractor relics compete on one side with each other for transient dominance, and on the other side with the dynamical influence of the input signals. Unsupervised and local Hebbian-style online learning then allows the system to build up correlations between the internal dynamical transient states and the sensory input stream. An emergent cognitive capability results from this set-up. The system performs online, and on its own, a nonlinear independent component analysis of the sensory data stream, all the time being continuously and autonomously active. This process maps the independent components of the sensory input onto the attractor relics, which acquire in this way a semantic meaning.     

Mixed papillary transitional cell carcinoma and adenocarcinoma of the uterine cervix: a clinicopathologic study of three cases.

Although tumors consisting of a combination of transitional cell carcinoma (TCC) and adenocarcinoma have been described in the endometrium, they have not been documented in the uterine cervix to our knowledge. Three such cervical cases are reported in this article. Three patients, whose ages ranged from 40 to 61 years, presented with vaginal bleeding and malignant cells on routine Papanicolaou smears. The initial diagnoses based on a biopsy specimen were poorly differentiated squamous cell carcinoma in two patients and adenocarcinoma with a solid component in the third patient. All patients underwent radical hysterectomy. The hysterectomy specimens each contained a polypoid endocervical mass with minimal invasion of the cervical stroma. On microscopic examination, each tumor consisted of a component of papillary TCC admixed with an adenocarcinoma of endometrioid type. Both carcinomatous components were immunoreactive for cytokeratin (CK) 7 but not CK20. The three patients were alive and disease-free from 10 months to 4 years postoperatively. Recognition of this unusual variant of cervical carcinoma is important to delineate its clinical and pathologic features and establish prognostic differences, if any, from other histologic subtypes of cervical carcinoma. Papillary TCC mixed with adenocarcinoma broadens the morphologic spectrum of transitional cell neoplasms of the uterine cervix.     

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: I. Effects of primary motor cortex rTMS.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity. METHODS: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H(2)(15)O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically. RESULTS: Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex. CONCLUSIONS: This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1.     

Fine structure of nuclear division and microgametogony ofEimeria nieschulzi Dieben, 1924

Nuclear division and microgametogony ofEimeria nieschulzi were studied by transmission electron microscopy. All nuclear divisions occurred in close proximity to the gamont surface with four centrioles situated between the nuclear envelope and the gamont plasmalemma. During early nuclear divisions, each nucleus had a rod or hourglass-shaped nucleolus, indicating that the nucleolus probably pinched in two during nuclear division. Nuclear divisions occurred by nearly centrally located intranuclear spindles. Two centrioles were associated with each centrocone. Spindle microtubules, which originated from each centrocone, either traversed to the other centrocone or terminated at kinetochores. Four to 6 chromosome-like structures were present in each dividing nucleus. The formation of 50 to 100 biflagellate microgametes occurred at the margin of the microgamont by a process similar to that described for other coccidian species. Microgametes were limited by a single membrane with a prominent glycocalyx, 13 nm thick.Based on a thesis submitted by G.J. Sibert to the Graduate School of the University of Montana in partial fulfillment of the requirements for the Master of Science degree     

Neurobiology of Bipolar Illness: Implications for Future Study and Therapeutics

Many findings implicating prefrontal cortical and limbic areas of the brain and endocrine systems in the neuropathology and pathophysiology of bipolar illness have greatly increased our understanding of the neurobiology of the illness. New imaging techniques such as PET, MRI, SPECT, and MRS have detailed more evidence of specific regional alterations in the brains of bipolar patients than was thought possible just 20 years ago. These methods are beginning to be used to help predict response to treatment. Examining the mechanisms of action of mood stabilizers (such as lithium, carbamazepine, and valproate) has provided clues to potential underlying neurobiological abnormalities in the illness. Recent studies of postmortem brain tissue have begun to confirm prefrontal cortical and limbic neurochemical and microstructural alterations in patients with bipolar illness compared with controls. It is postulated that it is the balance between primary pathological versus secondary adaptive alterations in gene expression in the illness and their enhancement or dampening by pharmacotherapy, that may determine the episodic course of mood fluctuations and remissions. Further examination of the pathophysiology and neurobiology of bipolar illness should lead to both more effective treatments and, potentially, secondary and even primary episode prevention.     

Imaging of the pelvis and hip

Imaging is basic in the orthopedic evaluation of hip disorders. For optimal evaluation of these images, the orthopedic surgeon must not only correlate normal anatomy and pathology with radiographic findings, but must also be familiar with the newer modalities of CT, magnetic resonance imaging and ultrasound and the role and place of these studies in the evaluation of musculoskeletal disorders. This article correlates normal anatomy of the hip with these modalities and discusses the details of these techniques, particularly CT and MRI, that are pertinent to the orthopedic surgeon.     

Possibilities and limitation of prenatal diagnosis and carrier determination for Duchenne and Becker muscular dystrophy using cDNA probes.

Two cDNA probes, cf23a and cf56a, identify deletions of selected exons in about 50% of our DMD/BMD patients. We have estimated the most likely order of the 11 exons detectable with both probes with respect to the different extensions of the deletions. In one of our BMD pedigrees, the observed deletion could be traced in the affected males through three generations. This result shows that with the use of cDNA probes detecting deletions, the only risk of error in genomic prenatal diagnosis is the general high frequency of new mutations for DMD/BMD. This is important progress in diagnosis compared to the 2 to 5% risk of misdiagnosis because of crossing over events using conventional linkage analysis with bridging or intragenic probes. The first prenatal diagnosis of an unaffected fetus of a woman who is a DMD carrier according to ultrasound examination is described. In one of our DMD males, the cDNA probe cf56a detects a deletion breakpoint. His sister also shows the altered band and is therefore a DMD carrier, while his mother has a totally normal band pattern. The interpretation of this observation could be either germline mosaicism or two identical new mutations. The identification of deletion breakpoints is a new diagnostic strategy, especially for carrier determination, which excludes misdiagnosis owing to crossing over events and the problems of dosage estimation. It is, however, limited by the low frequency of breakpoints detectable with cDNA probes. Therefore, the generation of new intron probes in this region is an important goal.