Immunoreactive pinopsin in pineal and retinal photoreceptors of various vertebrates

Studies of severe hypoxemic events, defined as an arterial oxygen saturation < 80% greater than 4 s in spontaneously breathing infants, have been limited. The purpose of our study was to examine the distribution of respiratory events that lead to a fall in oximetrically measured oxygen saturation by using breathing patterns, heart rate, and validated pulse oximetry analysis. A total of 161 hypoxemic events were detected in 18 of 30 premature infants studied. Using an inductive plethysmographic based monitor, a total of 460 h of cardiorespiratory monitor recordings were analyzed. Hypoxemic events were categorized as being the direct result of apnea (duration longer than 15 s) or pauses (duration 4-14 s) with either unchanged or lower end-expiratory lung volumes compared with the preevent breaths. The breaths in the preevent period were analyzed for volume, timing, and thoracoabdominal coordination indices. Forty of the 161 events (25%) were associated with apnea of which 80% (31/40) had a mixed/obstructive basis. Ninety-four of the 161 severe hypoxemic events (58%) were associated with pauses with unchanged end-expiratory lung volume. Twenty-two of the 161 events (14%) showed pauses with lower end-expiratory lung volume. There were 5/161 events (3%) with severe hypoxemia in which no pause was observed. Comparison of the preevent periods in each category showed significant differences for only percent tidal volume from initial calibration and arterial oxygen saturation. Sixty-two percent (100/161) of severe hypoxemic events were preceded by hypopneic values of percent tidal volume. Seventy-five percent (40/161) of these hypoxemic events and their etiology would have gone undetected using respiratory monitoring from impedance pneumograms and ECGs. The varied basis for these events underscores the importance of analyzing detailed respiratory wave forms along with movement-free signal of arterial oxygen saturation and ECG, to formulate appropriate intervention strategies.     

Influenza vaccination in 22 developed countries: an update to 1995

This study expands and updates through 1995 our earlier report on influenza vaccine use in 18 developed countries. Five of the six countries with high levels of vaccine use in 1992 (> or = 130 doses/1000 population) showed little change or slight declines over the subsequent 3 years. The exception was the United States, where a new federal program for vaccination reimbursement for the elderly helped to increase vaccine distribution from 144 to 239 doses/1000 population. The six countries with medium levels of vaccine use in 1992 (76-96 doses/1000 population) increased to > or = 100 doses/1000 population by 1995. Among the six low-use countries in 1992 (< or = 65 doses/1000 population), only Finland showed substantial improvement (96 doses/1000 population) in 1995. Four new countries were added to the study. In Germany, vaccine use increased to 80 doses/1000 population in 1995, but in Ireland it remained at a low level (48 doses/1000 population). In Korea, vaccine use increased from 17 to 95 doses/ 1000 population during the period 1987-1995. In Japan, very high levels of vaccine use (approximately 280 doses/1000 population) in the early 1980s were associated with vaccination programs for school children. However, vaccine use fell precipitously when these programs were discontinued, and only 2 and 8 doses/1000 population were used in 1994 and 1995, respectively. In all 22 countries, higher levels of vaccine use were associated with vaccination reimbursement programs under national or social health insurance and were not correlated with different levels of economic development. Excluding Japan, in 1995 there was still a greater than fourfold difference between the highest and lowest levels of vaccine use among the other 21 countries in the study. Given its well established clinical effectiveness and cost-effectiveness, none of these countries has yet achieved the full benefits of its programs for influenza vaccination.     

gp 120s derived from four syncytium-inducing HIV-1 strains induce different patterns of CD4 association with lymphocyte surface molecules

This work extends our previous finding that lymphocyte treatment with gp120IIIB specifically induces CD4 association with several surface molecules to other molecules and to three other gp120s from different HIV-1 strains. The ability to induce this association was displayed by the four gp120s employed, i.e. gp120IIIB, gp120SF2, gp120MN and gp120(451), and the association patterns were different, as shown by both co-capping and immunoprecipitation. Co-capping showed that all four gp120s significantly potentiated CD4 association with CD3, CD45RA, CD45RB, CD38, CD26, CD59 and class I MHC molecules. By contrast, CD4 association with CD95 was induced only by gp120(451) and gp120MN; that with CD11a only by gp120SF2 and gp120MN; and that with CD27 and CD45RO only by gp120MN and gp120(451) respectively. All gp120s induced significant CD4 association with CD49d, but gp120SF2 displayed a significantly weaker effect than gp120IIIB. Induction of association was not mediated by inside-out signaling via the CD4-associated tyrosine kinase p58lck, since it was not inhibited by the tyrosine kinase inhibitors herbymicin and genistein, nor by CD45 bridging between CD4 and the associating molecule, since similar patterns of association were detected IN cells expressing different CD45 isoform patterns. Moreover, it was not mediated by chemokine receptors interacting with the gp120 V3 loop, since RANTES did not alter the gp120-induced CD4 association pattern. By contrast, the observation that gp120s from four HIV-1 strains induce different CD4 association patterns suggests that gp120 directly interacts with the associating molecules, possibly via their hypervariable regions.     

Cortical and hippocampal volume deficits in temporal lobe epilepsy

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

Giant cell arteritis in Lugo, Spain, is associated with low longterm mortality

OBJECTIVE: To assess the longterm survival of patients with giant cell arteritis (GCA) in a well defined area in Northwestern Spain. METHODS: A followup study of consecutive biopsy proven patients with GCA diagnosed in Lugo, Spain January 1, 1982-March 31, 1996 was performed. Patients were followed from time of diagnosis until either their death or October 1, 1996. Time and cause of death were reviewed. Statistical methods included standardized mortality ratio (SMR), and Kaplan-Meier product-limit survival analysis. Cox proportional hazard models were used to identify clinical features and laboratory findings associated with survival. RESULTS: By October 1, 1996, full information about 109 biopsy proven patients with GCA (59 men/50 women) was available. The mean age +/- SD at the time of diagnosis was 73.9 +/- 7.3 years for women and 74.1 +/- 5.8 for men (p = NS). After a median followup of 54 months, 22 patients (20.2%) had died. Three died within the first month after diagnosis due to either vascular complications related to GCA or therapy complications. Apart from a history of severe underlying diseases (comorbid condition unrelated to GCA), neither sex nor any clinical features of GCA were significantly associated with an increase in mortality. As in the general population of the same age in Lugo, the majority of deaths were due to cardiovascular and cerebrovascular complications. SMR was 0.80 (95% CI 0.47-1.13). One, 2, 5, and 10 year survival rates were 95, 91, 81, and 62%, respectively. Hazard function was 1.8% at Day 30 after diagnosis and remained low until the end of the first year of treatment. Thereafter, mortality increased slightly. As this function was constant, we applied an exponential model. The estimated risk of death with this model was 5.3% per year. CONCLUSION: Longterm mortality of GCA in our area is low. However, it may be possible to further lower the mortality rate through early diagnosis and careful followup.     

Structure-function relations of variant and fragment nisins studied with model membrane systems

Nisin, a 34 residue lantibiotic produced by strains of Lactococcus lactis subsp. lactis, exerts antimicrobial activity against Gram-positive bacteria at the cytoplasmic membrane. The structural aspects of nisin which facilitate membrane interaction and permeabilization have been investigated in planar lipid bilayers and liposomes with proteolytic fragments and site-directed variants. N-Terminal nisin fragments N1-12 and N1-20 had little effect on phospholipid mobility, on macroscopic electrical conductance, or on calcein release from liposomes. By contrast, the I30W nisin A variant induced a time-dependent reduction in lipid mobility, indicative of nisin-membrane surface interactions, as well as a decline in membrane capacitance, rise in conductance, and calcein release from liposomes. In these respects I30W nisin A is similar to native nisin. Charge substitutions were also engineered to generate K12L and H27K nisin A variants, both of which were similar to I30W nisin A with respect to an overall reduction in phospholipid mobility. While the K12L nisin A variant elicited a higher increase in membrane capacitance and electrical conductance than I30W nisin A, the H27K nisin A variant elicited weaker effects. These results point to a substantial role for intramembrane charged residues in controlling ion flow through nisin-doped membranes. Native nisin and variants elicit an enhanced release of calcein from liposomes composed of the negatively-charged phospholipids cardiolipin and phosphatidylserine, compared with phospholipid bearing no net charge, suggesting that an electrostatic attraction encourages the initial nisin-membrane association. The results are discussed in the context of other recently proposed models for nisin action.     

SnoRNAs as tools for RNA cleavage and modification

Eukaryotic small nucleolar RNAs (snoRNAs) influence rRNA synthesis at two stages: nucleolytic processing and selection of nucleotides to be ribose methylated (Nm) or converted to pseudouridine (psi). The two modification functions and some processing activities involve direct base pairing of snoRNA with rRNA. In addition to rRNA-targeting sequences, snoRNA function depends on the presence of conserved box elements involved in snoRNA synthesis and localization. The present investigation is directed at using snoRNAs as tools for two purposes: 1) introducing nucleotide modifications into novel sites in rRNA and other snoRNAs, and: 2) targeting nucleolar RNAs for destruction using snoRNA:ribozyme chimers ('snorbozymes'). Early results demonstrate that snoRNAs can be used for both applications.