Early interleukin 4-dependent response can induce airway hyperreactivity before development of airway inflammation in a mouse model of asthma

In experimental models of bronchial asthma with mice, airway inflammation and increase in airway hyperreactivity (AHR) are induced by a combination of systemic sensitization and airway challenge with allergens. In this report, we present another possibility: that systemic antigen-specific sensitization alone can induce AHR before the development of inflammation in the airway. Male BALB/c mice were sensitized with ovalbumin (OVA) by a combination of intraperitoneal injection and aerosol inhalation, and various parameters for airway inflammation and hyperreactivity were sequentially analyzed. Bronchial response measured by a noninvasive method (enhanced pause) and the eosinophil count and interleukin (IL)-5 concentration in bronchoalveolar lavage fluid (BALF) gradually increased following the sensitization, and significant increase was achieved after repeated OVA aerosol inhalation along with development of histologic changes of the airway. In contrast, AHR was already significantly increased by systemic sensitization alone, although airway inflammation hardly developed at that time point. BALF IL-4 concentration and the expression of IL-4 mRNA in the lung reached maximal values after the systemic sensitization, then subsequently decreased. Treatment of mice with anti-IL-4 neutralizing antibody during systemic sensitization significantly suppressed this early increase in AHR. In addition, IL-4 gene-targeted mice did not reveal this early increase in AHR by systemic sensitization. These results suggest that an immune response in the lung in an early stage of sensitization can induce airway hyperreactivity before development of an eosinophilic airway inflammation in BALB/c mice and that IL-4 plays an essential role in this process. If this early increase in AHR does occur in sensitized human infants, it could be another therapeutic target for early prevention of the future onset of asthma.     

Detection of cytomegalovirus in urine samples by an enzyme-linked immunosorbent assay using a monoclonal antibody against the viral 150-kilodalton protein.

McKeating et al. (J.A. McKeating, P.D. Griffiths, and J.E. Grundy, J. Gen. Virol. 68:785-792, 1987; J. A. McKeating, J. E. Grundy, Z. Varghese, and P. D. Griffiths, J. Med. Virol. 18:341-348, 1986; J. A. McKeating, S. Stagno, P. R. Stirk, and P. D. Griffiths, J. Med. Virol. 16:367-373, 1985) reported previously that beta 2 microglobulin inhibits the detection of human cytomegalovirus (CMV) in urine specimens by an enzyme-linked immunosorbent assay (ELISA) with a monoclonal antibody against the glycoprotein of CMV. They postulated that beta 2 microglobulin binds to the viral glycoproteins and masks the antigenic determinants. We developed here an ELISA method for the detection of CMV in urine by using a monoclonal antibody against the viral 150-kDa protein to capture the viral antigen. This assay detected CMV both in culture medium and in urine specifically at concentrations higher than 10(3) PFU/ml and quantitatively at concentrations higher than 10(4) PFU/ml. The sensitivity of the ELISA increased about 10-fold when peroxidase-labeled F(ab')2 from goat anti-human immunoglobulin G was used as a secondary detecting antibody in combination with concentration of the virus in urine samples by ultracentrifugation. The inhibition of ELISA by beta 2 microglobulin was not observed in this ELISA system. When 56 urine specimens from renal transplant recipients were examined for CMV antigens, the ELISA system had a sensitivity of 78% and a specificity of 97%. The positive and negative predictive values of the assay were 95 and 86%, respectively. Furthermore, CMV antigens in urine were quantitated by the assay during the course of typical CMV disease of renal transplant recipient. These results suggest strongly that the measurement of CMV antigens in urine by our rapid and quantitative ELISA system provides very useful data for the monitoring of CMV infections in renal transplant recipients and making decisions about therapy.     

Lymphocyte proliferation in response to acute heavy resistance exercise in women: influence of muscle strength and total work

Little is understood about the immune responses to heavy resistance exercise. The purpose of this investigation was to determine the influence of physical strength and the ability to do more total work on lymphocyte proliferation after an acute bout of heavy resistance exercise. A group of 50 healthy but non-strength trained women were recruited for the study and tested for their one repetition maximum (i.e. 1 RM or maximal mass lifted once). From the normal distribution of strength the top and bottom 8 women [mean age 22.5 (SD 3.1) years] were asked to volunteer to define our two groups (i.e. high strength and low strength). The two groups were significantly different (P<0.05) in 1 RM squat strength [low strength 39.9 (SD 4.6) kg, 0.65 (SD 0.08) kg·kg body mass^–1 and high strength 72.2 (SD 10.7) kg, 1.1 (SD 0.12) kg·kg body mass^–1] but were not significantly different in body mass, age, activity levels, and menstrual status (all in same phase). Each performed a resistance exercise protocol consisting of six sets of 10 RM squats with 2 min rest between the sets. The 10 RM loads and total work were significantly greater in the high strength group than in the low strength group. Blood samples were obtained pre-exercise and immediately post-exercise for test for lactate (significant increase with exercise) and cortisol (no changes) concentrations with no differences noted between groups. Immunological assays on the blood samples determined the incorporation of tritiated thymidine by lymphocytes in responses to concanavalin A (ConA), phytohemagglutinin (PHA), and pokeweed mitogen (PWM). Following the squat exercise, there was a significant decrease in lymphocyte responsiveness to PWM in the high strength but not in the low strength group for both total proliferation and proliferation adjusted per B or T cell. On the other hand, lymphocytes from the low strength group proliferated to a significantly greater extent (adjusted per T cell) in response to ConA and PHA. These data indicate that the heavy resistance exercise protocol reduced the lymphocyte proliferative responses only in the stronger group of subjects. This effect may have been due to the high absolute total work and the greater exercise stress created by the resistance exercise protocol in the high strength group. Therefore, individuals performing at the same relative exercise intensity (i.e. 10 RM) in a resistance exercise protocol may have different immune responses stemming from differences in absolute total work performance. Electronic Publication     

Evaluation of noninvasive monitoring of preoxygenation

Administration of 100% oxygen before a "rapid-sequence" induction of anesthesia is recommended to prevent hypoxemia during induction. In the present study, we used a laser scattering analyzer to study the effectiveness of nitrogen washout from the lungs with oxygen wash into the lungs under two different preoxygenation regimens; 4 times of maximal breathing of 100% oxygen in one minute and normal tidal breathing of 100% oxygen for 3 minutes. The volunteers were healthy, ASA physical status 1, 22 to 33 years of age (26 +/- 3), 167 +/- 5 cm tall, and weighing 60 +/- 5 kg. Arterial blood saturation measured by a pulse oximeter was 97 while breathing 21% oxygen, and 99% while breathing 100% oxygen. Arterial oxygen tensions were 98 mmHg while breathing 21% oxygen, and over 480 mmHg while breathing 100% oxygen. Arterial carbon dioxide and end tidal carbon dioxide concentrations indicated that 4 time of maximal breathing in a minute leads to hyperventilation. The end-tidal oxygen concentration was not significantly different between before and after oxygen administration in two different regimens. End-tidal nitrogen concentration after tidal volume ventilation was lower than that of 4 breath in a minute. These results indicate that end-tidal nitrogen and oxygen could reflect arterial nitrogen and oxygen tensions during preoxygenation.     

Periodic isorhythmic dissociation during enflurane anesthesia in a patient with Sinus Bradycardia

Key words  dysrhythmia - isorhythmic dissociation - oscillation     

Establishment of 2 human thyroid-carcinoma cell-lines (8305c, 8505c) bearing p53 gene-mutations

New cell lines, designated 8305C and 8505C, were established from undifferentiated thyroid carcinomas of a 67 year-old-female patient and a 78-year-old-female patient, respectively. Pathologically both these primary undifferentiated carcinoma tissues contained residual well differentiated components, suggesting well differentiated to undifferentiated carcinoma progression. Cell kinetic analysis indicate that the cell population doubling time is 43 h for 8305C and 36 h for 8505C. The saturation density at confluency is 5.7 x 10(4) cells/cm2 for 8305C and 1.1 x 10(5) cells/cm2 for 8505C. To identify genetic changes that may have occurred in these two cell lines, tumor suppressor genes p53, Rb, APC and MCC were analyzed. Sequence analysis confirmed a C:G to T:A transition at the first base of p53 gene codon 273 in 8305C and a C:G to G:C transversion at the first base of p53 codon 248 in 8505C. Polymerase chain reaction-loss of heterozygosity assays confirmed allelic deletion of p53 gene from the 8505C cell line. Loss of heterozygosity of other tumor suppressor genes were not observed. Given that p53 mutations associate with undifferentiated carcinoma but not with well differentiated carcinoma during multistep carcinogenesis of the thyroid, these cell lines should prove useful for research into the role of p53 gene mutations in malignant transformation.     

Haemodynamic changes associated with thermodilution cardiac output determination during metabolic acidosis or hypoxic hypoxia in dogs

Haemodynamic alterations elicited by iced injectate during thermodilution cardiac output measurements were evaluated in the presence of metabolic acidosis or hypoxic hypoxia in 14 instrumented anaesthetized dogs. The alterations in some haemodynamic variables during slowing of the heart rate following injection of 3 ml iced injectate were slightly greater in metabolic acidosis and hypoxic hypoxia as compared to animals without metabolic acidosis or hypoxic hypoxia (P < 0.05), but the changes were clinically insignificant. No serious haemodynamic changes were found during any cardiac output measurement by thermodilution in the presence of metabolic acidosis or hypoxic hypoxia. The values of cardiac output measured by thermodilution correlated closely with those of pulmonary blood flow measured by an electromagnetic flowmeter in the metabolic acidosis and hypoxic hypoxia groups (r > 0.9). It is concluded that thermodilution using iced injectate will estimate right ventricular output accurately in conditions of metabolic acidosis and hypoxic hypoxia.