Phenyl Isocyanate-Induced Asthma in Rats Following a 2-Week Exposure Period

This study was conducted to assess the toxic effects of repeatedinhalation exposures to phenyl isocyanate vapor in male Wistarrats. Rats were exposed to design concentrations of 0, 1, 4,7, or 10 mg/m³ phenyl isocyanate air for 2 weeks (6 hr/day,5 days/week). The rats were assessed for normal toxicologicparameters, and pulmonary function tests, blood gas measurements,and analysis of bronchoalveolar lavage fluid (BALF) parameterswere utilized shortly after exposures as well as 2 months postexposure.The results indicated that rats exposed to 7 and 10 mg/m³ experienceddecreased body weights, hypoactivity, hypothermia, signs ofrespiratory tract irritation, delayed onset of mortality, andchanges in organweights. In addition, pulmonary function testsdemonstrated decreased forced expiratory flow rates and quasistaticlung compliance. Arterial blood gases showed an arterial hypoxemiaand changes consistent with a pronounced venous-admixture-likeperfusion, suggesting severe mismatch of the ventilation/perfusionrelationship. Delayed onset of mortality appeared to be associatedwith respiratory acidosis and hypoxernia. Biochemical and cellularcomponents in BALF complemented the results of the functionalalterations. Remarkable changes were indicated by increasedactivities of the BALF parameters, -GPT, protein, and sialicacid. Histopathological findings provided evidence of increasedsecretory cell activity and a concentration-dependent increasein goblet cell hyperplasia at concentrations of 4 mg/m³ andabove. In rats exposed to 7 mg/m³ further findings consistedof intraluminal inflammation of airways, hypertrophia of bronchialsmooth muscle, epithelial desquamation, and eosinophilia ofthe airways. A complete regression of morphological lesionswas not found in the animals exposed to 4 mg/m³ and above atthe 2-month postexposure time period. In conclusion, the damageto the airways comprise most of the features characteristicof chronic airway inflammation or asthma.     

Pulmonary Response to Toner upon Chronic Inhalation Exposure in Rats

Pulmonary Response to Toner upon Chronic Inhalation Exposurein Rats. MUHLE, H., BELLMANN, B., CREUTZENBERG, O., DASENBROCK,C., ERNST, H., KILPPER, R., MACKENZIE, J. C., MORROW, P., MOHR,U., TAKENAKA, S., AND MERMELSTEIN, R., Fundam. Appl. Toxicol.17, 280–299. A chronic inhalation study of a test tonerwas conducted by exposure of groups of F-344 rats for 6 hr/day,5 days/week for 24 months The test toner was a special Xerox9000 type xerographic toner, enriched in respirable-sized particlescompared to commercial toner, such that it was about 35% respirableaccording to the ACGlH criteria. The target test aerosol exposureconcentrations were 0, 1.0 (low), 4.0 (medium), and 16.0 (high)mg/m³. Titamum dioxide (5 mg/m³) and crystalline silicon dioxide(1 mg/m³), used as negative and pasitive controls for fibrogenicity,were also evaluated. Inhalation of the test toner or the controlmaterials showed no signs of overt toxicity. Body weight, clinicalchemistry values, food consumption, and organ weights were normalin the toner- and TiO₂-exposed groups, except for a 40% increasein lung weight in the toner highexposure group. All of the changesin the toner-exposed groups were restricted to the lungs orassociated lymph nodes. A chronic inflammatory response wasevident from the bronchoalveolar lavage parameters for the tonerhigh-exposure group. The incidence of primary lung tumors wascomparable among the three toner-exposed groups and the TiO²-exposed,and air-only controls, as well as consistent with historicalbackground levels A mild to moderate degree of lung fibrosiswas observed in 92% of the rats in the toner high-exposure group,and a minimal to mild degree of fibrosis was noted in 22% ofthe animals in the toner high-exposure group. The pulmonarychanges in the toner high-exposure group were smaller in magnitudethan those found in the crystalline silica-exposed group. Thecomparative fibrogenic potency of TiO², toner, and SiO² wasestimated to be 1:5:418 using a dasimetric model and assuminga common mechanistic basis. There were no pulmonary changesof any type at the toncr low-exposure level, which is most relevantin regard to potential human exposures The lung alterationsin the toner high-exposure group are interpreted in terms of"lung overloading," a generic response of the respiratory systemto saturation of its detoxification capacity. The maximum tolerateddose (MTD) criterion was met at the toner high (16 mg/m³)-exposurelevel.     

EVALUATION OF T4 AND T3 BINDING KINETICS IN THE THYROXINE BINDING GLOBULIN ABNORMALITY OF AUSTRALIAN ABORIGINES

Low serum total T4 associated with subnormal concentrations of thyroxine binding globulin (TBG) has been reported in up to 40% of euthyroid Australian aborigines. It has been suggested that these subjects show both diminished concentration of TBG and reduced TBG affinity for T4 (Sarne et al., 1985). We have compared 12 euthyroid aborigines with low T4 (total T4 44 +/- 5 nmol/l) and aborigines with normal T4 (T4 99 +/- 9 nmol/l, n = 12) using measurements of free T4 and T3 by equilibrium dialysis. TBG was measured both by RIA (Henning, Berlin, FRG) and a method dependent on T4 binding (Corning Immophase). Aborigines with low T4 showed lower levels of free T4 (12.6 +/- 0.6 cf. 18.7 +/- 1.0 pM), free T4 index (66 +/- 8 cf. 98 +/- 13), total T3 (1.1 +/- 0.2 cf. 1.6 +/- 0.3 nmol/l), TBG RIA (14.0 +/- 0.6 cf. 25.0 +/- 1.2 ng/l), and TBG Immophase (9.0 +/- 0.5 cf. 22.0 +/- 1.2 mg/l) (P less than 0.01), but free T3 (5.3 +/- 0.4 cf. 4.7 +/- 0.4 pM) and TSH (1.9 +/- 0.2 cf. 1.8 +/- 0.2 mU/l) were not significantly different from the values found in aborigines with normal T4. Scatchard analysis of T4 and T3 binding was performed using serum diluted 1 : 20,000 for T4 and 1 : 500 for T3 (barbitone buffer pH 8.6, 4 degrees C, dextran-coated charcoal separation). In euthyroid low T4 aborigines compared to those with normal T4, both T4 capacity (106 +/- 14 cf. 238 +/- 13 nM, P less than 0.01) and affinity (5.05 X 10(10) cf. 8.47 X 10(10) M-1, P less than 0.05) were significantly reduced. Similarly, both T3 capacity (62 +/- 10 cf. 154 +/- 16 nM, P less than 0.01) and affinity (1.67 X 10(9) cf. 2.28 X 10(9) M-1, P less than 0.02) were reduced. A substantial minority of euthyroid Australian aborigines have a TBG variant characterized by both reduced capacity and affinity of T4 and T3. These findings suggest that TBG may be both qualitatively and quantitatively abnormal in these subjects.     

Another case of a lymphocytotoxic antibody with blood group A1, Leb and A Led associated specificity

A lymphocytotoxic antibody with blood group A1 Leb, and A (A1 + A2) Led, associated specificity was found together with an anti-HLA-DR2 in the serum of a multiparous woman. The A1 Leb and A Led-antibodies could be absorbed with erythrocytes from persons with blood group A1 or A2, irrespective of their Lewis antigens, even if their lymphocytes reacted negatively in this antibody, leaving anti-HLA-DR2 in the serum. Lymphocytes of blood group A1 were able to absorb the anti-A1 Leb and -A Led, whereas those of A2 could only absorb the anti-A Led. Saliva from persons with blood groups A1 Le (a - b +), A2 Le (a- b +), A1 Le (a - b -), secretor, and A2 Le (a - b -), secretor, inhibited the anti-A1 Leb and -A Led when tested in the serum/saliva ratio 50:1, which was not the case with other ABO-Lewis combinations. The woman who produced this antibody has blood group O Le (a - b +) and secretes H, Lea and Leb substances in about the same amount as do other individuals with blood group O Le (a - b +) used as controls. The anti-A in her serum has equal titers against A1 Le (a + b -) and A1 Le (a - b +) red cells.     

The Excimer Laser: Current Knowledge and Future Prospects

We have developed a complete excimer laser and fiber-optic angioplasty system and successfully opened completely occluded blood vessels in humans. We use the 308 nm XeCL excimer laser and fiber-optic delivery system that can be passed through a catheter or over a guidewire. In this article, we describe the knowledge essential for the interventionalist using the device: the method for generating 308 nm laser light, laser-tissue interaction, healing after laser injury, and how the rate of laser ablation is controlled. Our initial experience using the excimer laser in the superficial femoral artery has been excellent. (J of Interv Cardiology; 1988;1:1)