Allergy to bumblebee venom. II. IgE cross-reactivity between bumblebee and honeybee venom

To obtain more information on IgE cross-reactivity between bumblebee venom and honeybee venom, we tested sera from venom-sensitized patients for specific IgE against venoms from the European bumblebee (Bombus terrestris), the North American bumblebee (Megabombus pennsylvanicus), and the honeybee (Apis mellifera). RAST, RAST-inhibition, and immunoblotting experiments indicate that bumblebee venom and honeybee venom contain venom-specific IgE-binding epitopes. These results suggest that immunotherapy using honeybee venom may not be effective in all bumblebee venom-allergic patients. Our experiments also revealed differences in IgE binding for venom from European and American bumblebees.     

Constitutive activation of opsin by mutation of methionine 257 on transmembrane helix 6

Rhodopsin is a member of the large family of G protein-coupled receptors (GPCR's). Constitutive activity of GPCR's, defined as ligand-independent signaling, has been recognized as an important feature of receptor function and has also been implicated in the molecular pathophysiology of a number of human diseases. Rhodopsin has evolved a unique mechanism to minimize receptor basal activity. The chromophore 11-cis-retinal, which acts as an inverse agonist in rhodopsin, is covalently bound to the receptor to ensure extremely low receptor signaling in the dark. In this study, we replaced Met257 in TM helix 6 of opsin with each of the remaining 19 amino acids. Only mutant opsin M257R failed to be expressed in COS-cell membranes. Each of the remaining 18 mutant opsins, with the exception of M257L, was significantly constitutively active. Two mutants in particular, M257Y and M257N, displayed very high levels of constitutive activity. In addition, the double-site mutants with substitutions of both Met257 and Glu113 in TM helix 3 tended to be much more constitutively active than the sums of the activities of the individual single-site mutants. Based on existing structural models of rhodopsin, we conclude that Met257 may form an important and specific interhelical interaction with a highly conserved NPXXY motif in TM helix 7, which stabilizes the inactive receptor conformation by preventing TM helix 6 movement in the absence of all-trans-retinal. Furthermore, we are able to show that the pharmacological properties of the large number (approximately 50) of mutant opsins that we have characterized to date support the two-state model of GPCR function. These results suggest that rhodopsin and other GPCR's share a common mechanism of receptor activation that involves specific changes in helix-helix interactions.     

Gap junctions and growth control in liver regeneration and in isolated rat hepatocytes

The hepatocytes in the mature normal liver are tightly coupled through gap junctions, except during compensatory hyperplasia (regeneration) after partial hepatectomy when the gap junctions become down-regulated. The significance of this down-regulation has been a long-standing enigma. The present study of hepatocytes in primary culture and in the regenerating liver aimed at defining the relationship, if any, between hepatocyte gap junctional communication and proliferation. Gap junctional down-regulation in the regenerating liver appeared to be a specific phenomenon because desmosomes and the surface contact area between neighboring hepatocytes remained constant. All agents and conditions (dexamethasone in vivo; dexamethasone, cyclic adenosine monophosphate, serum, and high cell density in vitro) delaying gap junctional down-regulation also increased the lag before the cells reached competence to enter S phase. This raised the possibility that hepatocyte DNA replication was inhibited through preservation of gap junctions. However, we disproved this assumption by showing that the DNA replication (more specifically the G1/S transition rate constant) was inhibited even in hepatocytes completely devoid of gap junctional communication. The teleological advantage of linking gap junctional down-regulation to hepatocyte G1 progression therefore may not be to trigger DNA replication but to ensure that proliferating hepatocytes and hepatocytes responsible for liver-specific metabolic functions maintain separate pools of metabolites and signaling molecules.     

May-Thurner syndrome: management by endovascular surgical techniques

In the winter of 1996, a total of 71 working adults from 20 to 60 (m = 37.3) years of age were immunized with one or two doses of inactivated influenza vaccine formulated in Japan. The reciprocal geometric mean hemagglutination inhibition antibody titers [mean HI] and the percentage with a hemagglutination inhibition titer of > or = x 128 [percent > or = x 128], against A/ Yamagata/32/89 (H1N1), A/Uhan/359/95 (H3N2), and B/Mie/1/93 were significantly elevated by either doses. The pre-/post-vaccination mean HI of H1N1 were 61.5/668.4 with one dose, and 85.7/637.3 with two doses. The percent > x 128 were 36.5/96.2 with one dose, and 47.4/94.7 with two doses. No significant differences were apparent between one and two doses. Similarly, nonsignificant differences were observed for the other two antigens contained in the vaccine. We observed the sufficient immune response to only one dose of inactivated influenza vaccine, which emphasizes the merit of one dose method of influenza immunization.     

Angiogenic activity of cervical carcinoma: assessment by functional magnetic resonance imaging-based parameters and a histomorphological approach in correlation with disease outcome

Angiogenesis plays a fundamental role in tumor growth and metastasis. What is needed is a quantitative, noninvasive, and repeatable assay to estimate functional angiogenic activity of the entire tumor. The aims of the present study were to: (a) examine the relationship between functional magnetic resonance imaging (MRI)-based parameters with established histomorphological markers of tumor angiogenesis [histological microvessel density (HMVD) and vascular endothelial growth factor expression (VEGF)]; and (b) determine the ultimate value of both approaches to assess functional angiogenic active hotspots as markers of disease outcome in patients with cancer of the uterine cervix. Pharmacokinetic parameters (amplitude A, tissue exchange rate constant k21) were calculated from contrast-enhanced dynamic MRI series in 57 patients (mean age, 49 +/- 14 years) with biopsy proven uterine cervical cancer. Both pharmacokinetic parameters were correlated to histomorphologically determined areas of high HMVD and VEGF expression obtained from the operative specimens after radical surgery. In addition, the functional MRI and histomorphological data were used to assess disease outcome. A significant association was found between HMVD and the amplitude A (P < 0.001) and a less pronounced association with k21, (P < 0.05), respectively. No significant associations were found between the pharmacokinetic parameters (A, k21) and VEGF expression. When stratified into high and low median k21 groups, median k21 values >5.4 min(-1) were the only significant (P < 0.05) factors in predicting poor patient survival. None of the histomorphological markers of angiogenesis (HMVD or VEGF expression) showed any predictive power. We have found that: (a) focal hotspots of HMVD are the pathophysiological basis for differences in functional MRI; (b) areas of high microvessel density and microvessel permeability do not necessarily coincide, as demonstrated by the histomorphological and functional MRI findings; (c) the functional angiogenic activity of a tumor may not be sufficiently characterized by a histomorphological approach but rather by a functional MRI-based approach; and (d) functional MRI-based analysis may assess tumor angiogenic activity in terms of disease outcome more comprehensively than the histomorphological approach.     

Incidence, survival and mortality in cervical cancer in Norway, 1956-1990

Long-term trends in incidence, survival and mortality were examined in women with squamous cell carcinoma and adenocarcinoma of the uterine cervix, diagnosed in Norway in the 35-year period 1956-1990. During the 1970s the number of cervical smears increased substantially in Norway, although no organised screening programme was introduced. Special attention was paid to the time period 1971-1990 to evaluate the effect of the extensive spontaneous screening. In addition, the prognostic importance of clinical stage and age was explored. In the squamous cell carcinoma patients the incidence rate peaked in the time period 1971-1975, since when there has been a decrease. In the adenocarcinoma patients the incidence rate rose through the years 1976-1990. Also, the proportion of adenocarcinomas increased in this time period. The mortality rates in both histological types declined modestly through the years 1966-1990. A more favourable stage distribution was noted among the squamous cell carcinomas (P = 0.00), but not among the adenocarcinomas, when comparing the two diagnostic periods 1971-1975 and 1981-1985. The multivariate analysis (GLIM) revealed that stage was the most important prognostic factor in both histological types (P = 0.00). In the squamous cell carcinoma patients the relative rate increased (P = 0.04) in the last period. There was a tendency towards a poorer prognosis in younger women in this group, but age did not prove to be an important prognostic factor (P = 0.08).     

U. S. medical graduates versus foreign medical graduates. Are there performance differences in practice?

This study has attempted to determine the relationship between physicians' medical education and their performances (technical quality and utilization of medical care resources) in offices and hospitals. The sample consisted of 506 physicians of Hawaii, involving 18 specialty categories. The study finds little evidence of the influence of the type of medical schools on physicians' technical quality and utilization of medical resources in practice. The mean differences between the categories of medical schools were not statistically significant (except for the quality when specialists practiced within their own areas of specialization). There is no evidence that all categories of U.S. medical graduates provided a higher quality care and better utilization than all categories of foreign medical graduates. There was no consistent pattern of performances within the categories of U.S. medical schools and of foreign medical schools in these dimensions of performances.     

Prevalence and risk factors for HBV infection among street youth in central Brazil

PURPOSE: A seroprevalence survey was carried out among 496 street adolescents from 9 to 20 years old in central Brazil to determine the prevalence of hepatitis B (HBV) markers, as well as to assess the role of potential risk factors. RESULTS: The findings reveal that 20.4% of the participants were homeless adolescents without family links, living and/or working on the streets. The age at first sexual intercourse was as low as 9 years old, and approximately 60% of this population had had at least one sexual relationship by the age of thirteen, indicating prepubertal initiation of sexual experiences among street adolescents. 13.5% were HBV marker-positive (anti-HBc) and 2.0% had antigenemia. Street-based youth had a higher HBV marker-positive rate when compared to home-based teens (OR = 4.1, 95% CI: 2.1-8.5) and, similarly, higher HBV prevalence was obtained for those reporting sexual activity versus the group without sexual activity (OR = 2.1, 95% CI: 1.1-3.9), even after adjusting for potential confounders. CONCLUSIONS: We have found that street youth, particularly street-based adolescents, should be considered at-risk group for hepatitis B infection in our region. These findings may be used as a baseline information for policy changes not only in hepatitis B prevention but also to reverse the scenario of adolescents sexual abuse.     

Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group

Intravenously administered ciprofloxacin was compared with imipenem for the treatment of severe pneumonia. In this prospective, randomized, double-blind, multicenter trial, which included an intent-to-treat analysis, a total of 405 patients with severe pneumonia were enrolled. The mean APACHE II score was 17.6, 79% of the patients required mechanical ventilation, and 78% had nosocomial pneumonia. A subgroup of 205 patients (98 ciprofloxacin-treated patients and 107 imipenem-treated patients) were evaluable for the major efficacy endpoints. Patients were randomized to receive intravenous treatment with either ciprofloxacin (400 mg every 8 h) or imipenem (1,000 mg every 8 h), and doses were adjusted for renal function. The primary and secondary efficacy endpoints were bacteriological and clinical responses at 3 to 7 days after completion of therapy. Ciprofloxacin-treated patients had a higher bacteriological eradication rate than did imipenem-treated patients (69 versus 59%; 95% confidence interval of -0.6%, 26.2%; P = 0.069) and also a significantly higher clinical response rate (69 versus 56%; 95% confidence interval of 3.5%, 28.5%; P = 0.021). The greatest difference between ciprofloxacin and imipenem was in eradication of members of the family Enterobacteriaceae (93 versus 65%; P = 0.009). Stepwise logistic regression analysis demonstrated the following factors to be associated with bacteriological eradication: absence of Pseudomonas aeruginosa (P < 0.01), higher weight (P < 0.01), a low APACHE II score (P = 0.03), and treatment with ciprofloxacin (P = 0.04). When P. aeruginosa was recovered from initial respiratory tract cultures, failure to achieve bacteriological eradication and development of resistance during therapy were common in both treatment groups (67 and 33% for ciprofloxacin and 59 and 53% for imipenem, respectively). Seizures were observed more frequently with imipenem than with ciprofloxacin (6 versus 1%; P = 0.028). These results demonstrate that in patients with severe pneumonia, monotherapy with ciprofloxacin is at least equivalent to monotherapy with imipenem in terms of bacteriological eradication and clinical response. For both treatment groups, the presence of P. aeruginosa had a negative impact on treatment success. Seizures were more common with imipenem than with ciprofloxacin. Monotherapy for severe pneumonia is a safe and effective initial strategy but may need to be modified if P. aeruginosa is suspected or recovered from patients.     

Primary structure of proteins from the wing cuticle of the migratory locust, Locusta migratoria

Wing cuticle from pharate adult locusts, Locusta migratoria, contains several prominent proteins which occur as minor components or are completely absent in other cuticular regions. Six of the wing-specific proteins have been purified and their amino acid sequences determined by combined use of mass spectrometry and automated Edman degradation. During the sequence determination very long sequence runs (90-121 residues) were necessary in order to establish the primary structure. All the wing-specific cuticular proteins from locusts contain the repeated short sequence motif -Ala-Ala-Pro-Ala/Val-, which is common for all hitherto sequenced cuticular proteins from pharate locusts. Several of the wing-specific proteins also possess an N-terminal region rich in glycine, tyrosine and leucine, characteristic for many locust cuticular proteins. Two of the analysed proteins have a conserved 61-residue sequence in common with a previously sequenced protein from locust wing cuticle and with two proteins from the pharate cuticle of adult Tenebrio molitor. Possible roles for the various sequence motifs are discussed.