Effects of membrane voltage on receptive field properties of lateral geniculate neurons in the cat: contributions of the low-threshold Ca2+ conductance.

1. Thalamic relay cells, including those of the lateral geniculate nucleus, display a low-threshold spike (LT spike), which is a large depolarization due to an increased Ca2+ conductance. Typically riding the crest of each LT spike is a burst of from two to seven action potentials, which we refer to as the LT burst. The LT spike is voltage dependent, because if the cell's resting membrane potential is more depolarized than roughly -60 mV, the LT spike is inactivated, but if more hyperpolarized, the spike is deinactivated and can be activated by a depolarization, such as from an afferent excitatory postsynaptic potential (EPSP). Thalamic relay cells thus display two response modes: a relay or tonic mode, when the cell is depolarized and LT spikes are inactivated, leading to tonic firing of action potentials; and a burst mode, when the cell is hyperpolarized and tends to respond with LT spikes and their associated bursts of action potentials. 2. We were interested in the contribution of the LT spike on the transmission of visually evoked signals through geniculate relay cells to visual cortex. We recorded intracellularly from geniculate cells in an anesthetized, paralyzed, in vivo cat preparation to study the effects of membrane voltage, and thus the presence or absence of LT spikes, on responses to drifting sine-wave gratings. We monitored the visually evoked responses of 14 geniculate neurons (6 X, 7 Y, and 1 unclassified) at different membrane potentials at which LT spikes were inactivated or deinactivated. 3. Changing membrane voltage during visual stimulation switched the response mode of every cell between the relay and burst modes. In the burst mode, LT spikes occurred in phase with the visual stimulus and not at rhythmic intervals uncorrelated to visual stimuli. To any given stimulus cycle, the cell responded usually with an LT burst or a tonic response, and rarely was more than one LT burst evoked by a stimulus cycle. Occasionally a single cycle evoked both an LT burst and tonic response, but always the LT burst occurred first. 4. The spatial tuning characteristics of the cells did not differ dramatically as a function of membrane potential, because the tuning of the LT bursts was quite similar to that of the tonic response component. Although we did not obtain complete temporal tuning properties, we did note that hyperpolarized cells responded reliably with LT bursts at several temporal frequencies. 5. A consistent difference was seen between the LT burst and tonic response components in terms of response linearity.(ABSTRACT TRUNCATED AT 400 WORDS)     

Respiratory syncytial virus infection and virus-induced inflammation are modified by contaminants of indoor air

The airway epithelium is the first cellular component of the lung to be encountered by the particles and pathogens present in inhaled air. In addition to its role as a physical barrier, the immunological activity of the airway epithelium is an essential part of the pulmonary immune system. This means that the symptoms of lung diseases that involve immunological mechanisms are frequently exacerbated by infection of the airway epithelium with respiratory viruses. The virus-induced enhancement of immunological activity in infected epithelial cells is well characterized. However, the effects that contaminants of inhaled air have upon the infectivity and replication of respiratory viruses and the inflammation they cause, are comparatively unknown. In this study, we have shown that pre-exposure of airway epithelial cells to bacterial lipopolysaccharides or a proteolytically active house dust mite allergen, is able to, respectively, inhibit or enhance the level of cellular infection with respiratory syncytial virus and similarly alter virus-induced expression of the inflammatory chemokine interleukin-8. These results suggest that respiratory syncytial virus infection and the inflammation caused by respiratory syncytial virus may be modified by the biologically active contaminants of indoor air.     

Enhanced mitochondrial degradation of yeast cytochrome c with amphipathic structures

The dispensable N-terminus of iso-1-cytochrome c (iso-1) in the yeast Saccharomyces cerevisiae was replaced by 11 different amphipathic structures. Rapid degradation of the corresponding iso-1 occurred, with the degree of degradation increasing with the amphipathic moments; and this amphipathic-dependent degradation was designated ADD. ADD occurred with the holo-forms in the mitochondria but not as the apo-forms in the cytosol. The extreme mutant type degraded with a half-life of approximately 12 min, whereas the normal iso-1 was stable over hours. ADD was influenced by the ⁺/^– state and by numerous chromosomal genes. Most importantly, ADD appeared to be specifically suppressed to various extents by deletions of any of the YME1, AFG3, or RCA1 genes encoding membrane-associated mitochondrial proteases, probably because the amphipathic structures caused a stronger association with the mitochondrial inner membrane and its associated proteases. The use of ADD assisted in the differentiation of substrates of different mitochondrial degradation pathways.     

Expansions and contractions of the FMR1 CGG repeat in 5,508 transmissions of normal,intermediate, and premutation alleles

Instability of the FMR1 repeat, commonly observed in transmissions of premutation alleles (55–200 repeats), is influenced by the size of the repeat, its internal structure and the sex of the transmitting parent. We assessed these three factors in unstable transmissions of 14/3,335 normal (~5 to 44 repeats), 54/293 intermediate (45–54 repeats), and 1561/1,880 premutation alleles. While most unstable transmissions led to expansions, contractions to smaller repeats were observed in all size classes. For normal alleles, instability was more frequent in paternal transmissions and in alleles with long 3′ uninterrupted repeat lengths. For premutation alleles, contractions also occurred more often in paternal than maternal transmissions and the frequency of paternal contractions increased linearly with repeat size. All paternal premutation allele contractions were transmitted as premutation alleles, but maternal premutation allele contractions were transmitted as premutation, intermediate, or normal alleles. The eight losses of AGG interruptions in the FMR1 repeat occurred exclusively in contractions of maternal premutation alleles. We propose a refined model of FMR1 repeat progression from normal to premutation size and suggest that most normal alleles without AGG interruptions are derived from contractions of maternal premutation alleles.     

Fulminant disseminated Varicella Zoster virus infection without skin involvement.

BACKGROUND: Varicella Zoster virus (VZV) infection is potentially very serious in bone marrow transplant recipients, and may manifest as a disseminated visceral infection. This condition is generally accompanied by a vesicular rash. OBJECTIVES: We review here a case of fulminant fatal disseminated VZV infection, not accompanied by skin involvement, and the laboratory approaches currently available to diagnose this disease. STUDY DESIGN: Post mortem tissue samples were subjected to histopathological examination, and tested for herpesviruses by electron microscopy and PCR. RESULTS: Intranuclear inclusions were noted by histological examination in the lungs, liver, kidneys and bone marrow. Particles with a herpesvirus morphology were visualized in liver tissue. VZV DNA was detected in liver and bone marrow by PCR followed by sequencing of the amplicons. Viremia was documented by retrospective testing of the serum by PCR. CONCLUSIONS: A disseminated VZV infection which proved rapidly fatal was demonstrated in a case without skin manifestations. This rare presentation of VZV infection is potentially underdiagnosed. Testing for VZV viremia by PCR can at the very least suggest the diagnosis although whether plasma-associated viremia is truly pathognomonic of visceral disseminated infection remains to be established.     

Transvaginal sonographic assessment of cervical length changes during triplet gestation

The current study aimed to evaluate the contribution of transvaginal sonography (TVS) for monitoring cervical changes during the second half of triplet gestation. Forty-five pregnant women with triplets pregnancies were prospectively scanned by TVS from approximately 26 weeks gestation and were longitudinally followed-up until delivery. Based on a receiver-operating curve it was found that a cervical length of 25 mm is the most accurate parameter (94% sensitivity and 45% specificity) for predicting premature delivery < or =33 gestational weeks. Thus, a single cervical length measurement of < or =25 mm at 26 weeks gestation correlated well with premature delivery at < or =33 weeks (chi(2); P = 0.002). Using the linear regression model, a mathematical equation [(Week of delivery = 27.4 + 1.6 x cervical length; R(2) = 0.46; P = 0.01)] for predicting the gestational age of delivery (dependent variable) was determined based on mid-gestation cervical measurements (predictors). In parturient women with triplet gestation, TVS assessment of the uterine cervix offers insight into the cervical status and provides valuable information for prenatal care. This includes both monitoring the cervical changes throughout third trimester as well as predicting the likelihood of premature delivery.     

Peritoneal implantation of meningeal melanosis via ventriculoperitoneal shunt: A case report and review of the literature

Systemic spread of primary intracranial neoplasms is rare and may be due to ventriculoperitoneal shunt (VPS). The most common tumors to metastasize via VPS are germinoma of the pineal gland and medulloblastoma. We report a case of 16-yr-old girl with central nervous system malignant melanosis who developed subsequent peritoneal implants via VPS. To the best of our knowledge, this patient represents the third reported case of meningeal melanosis or melanoma which metastasized to the peritoneal cavity via VPS. The VPS should be considered as possible mode of systemic spread in patients with primary cranial malignancy. © 1995 Wiley-Liss, Inc.     

A concept-based retrieval system for thoracic radiology

Current digital information systems in radiology are insufficient to accommodate the retrieval needs of academicians. Significant efforts are required in retrieving clinical cases for teaching and research. We describe a prototype system that supports intelligent case retrieval based on a combined specification of patient demographics, radiologic findings, and pathologic diagnoses. The documents for these cases can be distributed among multiple heterogeneous data bases. The system features automatic indexing of radiology and pathology reports, a comprehensive lexicon for thoracic radiology, an interface to a hospital information system, radiology information system, and picture archiving and communication systems, and a graphical user interface for query formulation and results visualization. The prototype system was developed within the domain of thoracic radiology involving patients with lung cancer.     

Citrobacter rodentium lifA/efa1 is essential for colonic colonization and crypt cell hyperplasia in vivo

Previously, we have identified a large gene (lifA, for lymphocyte inhibitory factor A) in enteropathogenic Escherichia coli (EPEC) encoding a protein termed lymphostatin that suppresses cytokine expression in vitro. This protein also functions as an adhesion factor for enterohemorrhagic E. coli (EHEC) and Shiga toxin-producing E. coli and is alternatively known as efa1 (EHEC factor for adherence 1). The lifA/efa1 gene is also present in Citrobacter rodentium, an enteric pathogen that causes a disease termed transmissible murine colonic hyperplasia (TMCH), which induces colitis and massive crypt cell proliferation, in mice. To determine if lifA/efa1 is required for C. rodentium-induced colonic pathology in vivo, three in-frame mutations were generated, disrupting the glycosyltransferase (GlM12) and protease (PrMC31) motifs and a domain in between that does not encode any known activity (EID3). In contrast to infection with wild-type C. rodentium, that with any of the lifA/efa1 mutant strains did not induce weight loss or TMCH. Enteric infection with motif mutants GlM12 and PrM31 resulted in significantly reduced colonization counts during the entire 20-day course of infection. In contrast, EID3 was indistinguishable from the wild type during the initial colonic colonization, but cleared rapidly after day 8 of the infection. The colonic epithelium of all infected mice displayed increased epithelial regeneration. However, significantly increased regeneration was observed by day 20 only in mice infected with the wild-type in comparison to those infected with lifA/efa1 mutant EID3. In summary, lifA/efa1 is a critical gene outside the locus for enterocyte effacement that regulates bacterial colonization, crypt cell proliferation, and epithelial cell regeneration.