Modification of rat brain Kv1.4 channel gating by association with accessory Kvβ1.1 and β2.1 subunits

 We have examined the effects of co-expression of Kvβ1.1 and Kvβ2.1 subunits on the gating of rat brain Kv1.4 channels, expressed in Xenopus oocytes. Expression of Kv1.4 subunits alone produced a rapidly inactivating ”A” type current, which activated at potentials beyond –60 mV in a solution containing high levels of rubidium. Current activation curves obtained from tail current measurements were fitted with a Boltzmann function, with V _1/2 = –47 mV and k = 10 mV. Neither the Kvβ1.1 nor Kvβ2.1 subunits altered the voltage dependence of activation. Both subunits accelerated the activation time constant of Kv1.4, without affecting its voltage dependence. Surprisingly, the Kvβ2.1 subunit, which lacks an N-terminal inactivation domain, was almost as effective as the Kvβ1.1 subunit in speeding up Kv1.4. Steady-state inactivation of Kv1.4 was unchanged upon co-expression with either Kvβ1.1 or Kvβ2.1 subunits. Kv1.4 recovered from inactivation with two time constants; apart from an ≈ 50% lengthening of the slow time constant with a high Kvβ2.1 injection ratio, neither time constant was altered by either the Kvβ1.1 or Kvβ2.1 subunits, suggesting little interaction with recovery from C-type inactivation. Clearly, β subunits have the potential to modify the gating of Kv1.4 channels in the brain more subtly than has been suggested previously. Received: 17 March 1997 / Accepted: 30 June 1997     

Long-term evaluation of five biomaterials for angioplastic enlargement of the pulmonary artery in a young dog model

In 45 young dogs an enlargement angioplasty of the left pulmonary artery was performed using patches made from one of three autologous materials (jugular vein, unmodified pericardium, and glycerolized pericardium) or from two heterologous materials (lyophilized human dura mater and modified bovine carotid artery). Catheterization and angiographic studies performed 5 to 6 months after the operation showed that all patched vessels had remained patent, except in three dogs which had received heterologous implants. The animals were killed 5-24 months after operation (mean weight increase: 84%), and the implants were studied by optical microscopy and morphometry, scanning and transmission electron microscopy, and indirect immunofluorescence with antidog Factor VIII rabbit antiserum. The two heterologous tissues exhibited limited biocompatibility, as estimated from 10 criteria obtained at histologic studies. Conversely, all three autologous biomaterials were characterized by infiltration of noninflammatory cells, near-complete endothelialization, and neosynthesis of structural proteins; infectious foci were very rare or absent. These results suggest that autologous tissues, although deendothelialized at the time of implantation, constitute the most suitable material for patch angioplasty, as far as endothelial triggering, cellularity and resistance to infection are concerned.     

Interactions of Respiratory and Cardiovascular Adjustments to Behavioral Stressors

The relationships among a variety of cardiovascular and respiratory measures were examined in young college males subjected to a cold pressor task, reaction-time shock avoidance task, and three levels of graded exercise. As expected, the relationships between cardiovascular (e.g., heart rate and cardiac output) and respiratory (e.g., oxygen uptake and minute ventilation) variables were tightly linear when considering rest and exercise values. However, the range of individual cardiopulmonary responses during cold pressor and reaction time was considerable, often leading to disruptions in the cardiovascular/respiratory interactions. Analyses of extreme high and low ventilation reactors during both reaction time and cold pressor revealed that the excessive ventilation responders in cold pressor showed clear signs of hyperventilation. Increases in ventilation by the high reactors during reaction time were of smaller magnitude than during cold pressor, with potential hyperventilation much less clear. Increases in minute ventilation by reactors during the cold pressor task were primarily due to large increases in tidal volume, with only modest increases in respiratory rate. For reaction time, however, the increases in ventilation by reactive individuals stemmed from rate increases with tidal volume remaining essentially unchanged.     

CORRELATION OF SKIN POTENTIAL AND SKIN RESISTANCE MEASURES

Simultaneous measurements of skin potential (SP) and skin resistance (SR) obtained from 20 male and 20 female adult subjects during 2 sessions held 2 to 9 days apart were used in studying (1) the correlation of change measurements and prestimulus level in the two measures, and (2) the amount of correlation between SP and SR using both simple difference and residual change scores in which the regression of poststimulus values on initial level (prestimulus) has been controlled. Correlations within Ss and correlations among Ss showed large individual variability, correlation differences between males and females, and high correlation between SP and SR change scores. Although the law of initial value (LIV) seemed to have little applicability to the measurement of electrodermal responses, the results underscored the need to control for contamination of change measures by initial level regardless of direction.     

Nuclear organization of centromeric domains is not perturbed by inhibition of histone deacetylases

It is well established that modification of lysines in histone molecules correlates with gene expression and chromatin structure. It is not known whether this operates entirely at a local level, e.g. through the recruitment of specific proteins, or whether histone modifications might impact on more long-range aspects of chromatin organization. There is a distinctive organization of chromatin within the nucleus and the chromatin at the nuclear periphery of mammalian cells appears to be hypoacetylated. Previously it had been suggested that inhibition of histone deacetylases by TSA causes a gross remodeling of nuclear structure, specifically the recruitment of centromeric heterochromatin to the nuclear periphery. Here, we have quantified the nuclear organization of histone modifications and the localization of centromeric domains in human cells before and after TSA treatment. TSA alters the nuclear distribution of histone acetylation, but not that of histone methylation. TSA elevates levels of histone acetylation at the nuclear periphery but we see no alteration in the position of centromeric domains in the nuclei of treated cells. We conclude that the distinctive nuclear localization of centromeric domains is independent of histone acetylation.     

Primary pulmonary adenoid cystic carcinoma: report of a case diagnosed by fine-needle aspiration cytology

Adenoid cystic carcinoma of the lower respiratory tract is an uncommon tumor that can arise in the mainstem bronchus and often presents as an endobronchial mass lesion causing bronchial obstruction with post obstructive atelectasis and pneumonia. Exfoliative cytology is seldom useful in the diagnosis of primary bronchial adenoid cystic carcinoma, because these neoplasms usually have a submucosal location with often intact mucosa. Since most endobronchial adenoid cystic carcinomas are endoscopically visible, bronchoscope-guided fine-needle aspiration constitutes an excellent approach to establish a pathologic diagnosis. The fine-needle aspiration cytology of primary pulmonary adenoid cystic carcinoma has been rarely described. We report a case of primary adenoid cystic carcinoma of the lung having characteristic cytologic features and correlate with computed tomography, bronchoscopic, and histological findings. Bronchoscope-guided aspiration cytology provided a conclusive diagnosis of adenoid cystic carcinoma, which was further corroborated by histology in the pneumonectomy specimen. Diagn. Cytopathol. 2004;30:51-56.     

Distribution of the serotonin 2C (5HT2C) receptor gene -759C/T polymorphism in patients with schizophrenia and normal controls

BACKGROUND: In patients with schizophrenia, the percentage of patients with diabetes has been found to be twice that of the normal population. The risk factors for this higher rate are unknown, although dietary, lifestyle, and genetic factors have all been suggested. Recently, a polymorphism (-759C/T) in the serotonin 2C (5HT2C) receptor promoter region has been associated with the development of diabetes in a normal control population, with the frequency of the T allele being higher in subjects without diabetes. AIM: To determine whether the distribution of the -759C/T polymorphism of the 5HT2C receptor is different among patients with schizophrenia and normal controls. METHODS: DNA from 100 patients with schizophrenia and 81 normal controls were analyzed for the 5HT2C receptor -759C/T polymorphism to determine its allelic frequencies in these two groups. RESULTS: Using a chi-squared analysis, no statistical differences in the distribution of C alleles and T alleles were found between the two groups (P=0.2931). CONCLUSIONS: Patients with schizophrenia have a higher risk for developing diabetes than the general population. We did not find a higher distribution of the -759T allele of the 5HT2C receptor in normal controls compared with in patients with schizophrenia. This suggests the higher prevalence of diabetes in schizophrenia is not due to this polymorphism.     

Persistent electrical coupling and locomotory dysfunction in the zebrafish mutant shocked

On initial formation of neuromuscular junctions, slow synaptic signals interact through an electrically coupled network of muscle cells. After the developmental onset of muscle excitability and the transition to fast synaptic responses, electrical coupling diminishes. No studies have revealed the functional importance of the electrical coupling or its precisely timed loss during development. In the mutant zebrafish shocked (sho) electrical coupling between fast muscle cells persists beyond the time that it would normally disappear in wild-type fish. Recordings from sho indicate that muscle depolarization in response to motor neuron stimulation remains slow due to the low-pass filter characteristics of the coupled network of muscle cells. Our findings suggest that the resultant prolonged muscle depolarizations contribute to the premature termination of swimming in sho and the delayed acquisition of the normally rapid touch-triggered movements. Thus the benefits of gap junctions during early synapse development likely become a liability if not inactivated by the time that muscle would normally achieve fast autonomous function.