Effect of ventilation on vascular permeability and cyclic nucleotide concentrations in ischemic sheep lungs

Ventilation during ischemia attenuates ischemia-reperfusion lung injury, but the mechanism is unknown. Increasing tissue cyclic nucleotide levels has been shown to attenuate lung ischemia-reperfusion injury. We hypothesized that ventilation prevented increased pulmonary vascular permeability during ischemia by increasing lung cyclic nucleotide concentrations. To test this hypothesis, we measured vascular permeability and cGMP and cAMP concentrations in ischemic (75 min) sheep lungs that were ventilated (12 ml/kg tidal volume) or statically inflated with the same positive end-expiratory pressure (5 Torr). The reflection coefficient for albumin (sigmaalb) was 0.54 +/- 0.07 and 0.74 +/- 0. 02 (SE) in nonventilated and ventilated lungs, respectively (n = 5, P < 0.05). Filtration coefficients and capillary blood gas tensions were not different. The effect of ventilation was not mediated by cyclic compression of alveolar capillaries, because negative-pressure ventilation (n = 4) also was protective (sigmaalb = 0.78 +/- 0.09). The final cGMP concentration was less in nonventilated than in ventilated lungs (0.02 +/- 0.02 and 0.49 +/- 0. 18 nmol/g blood-free dry wt, respectively, n = 5, P < 0.05). cAMP concentrations were not different between groups or over time. Sodium nitroprusside increased cGMP (1.97 +/- 0.35 nmol/g blood-free dry wt) and sigmaalb (0.81 +/- 0.09) in nonventilated lungs (n = 5, P < 0.05). Isoproterenol increased cAMP in nonventilated lungs (n = 4, P < 0.05) but had no effect on sigmaalb. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester had no effect on lung cGMP (n = 9) or sigmaalb (n = 16) in ventilated lungs but did increase pulmonary vascular resistance threefold (P < 0.05) in perfused sheep lungs (n = 3). These results suggest that ventilation during ischemia prevented an increase in pulmonary vascular protein permeability, possibly through maintenance of lung cGMP by a nitric oxide-independent mechanism.     

The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus

The British Isles Lupus Assessment Group (BILAG) index is a computerized index for measuring clinical disease activity in systemic lupus erythematosus (SLE), which was developed according to the principle of the physician's 'intention to treat'. The index allocates separate alphabetic scores to each of eight organ-based systems; a total score is not calculated. This study demonstrated good between-rater reliability for the BILAG index for each organ-based system. There was no evidence of bias between observers. The BILAG index had good overall sensitivity (87%) and specificity (99%) when compared with the 'gold standard' criterion (starting or increasing disease-modifying therapy). There were high positive predictive values overall (80%), and for each organ-based system, with the exception of the neurological system.     

Prognostic value of urinary albumin excretion rate and other risk factors in elderly diabetic patients and non-diabetic control subjects surviving the first 5 years after assessment

In 1981-1982 urinary albumin excretion rates were determined in 211 diabetic and 216 non-diabetic subjects aged 60-74 years. By April 1992 122 diabetic and 58 non-diabetic probands had died. Dividing the two study populations at an albumin excretion rate of 15 micrograms/min showed that 69.3% of diabetic subjects with values at or above the limit, and 49.9% of those with values below (log rank test p = 0.0082) had died. The corresponding values for non-diabetic subjects were 44.4% and 21.0%, respectively (log rank test p = 0.0002). In single factor log rank tests ischaemic heart disease and a low value of HDL were also predictive of death in the diabetic population during a 10-11-year observation period. In the non-diabetic population ischaemic heart disease, hypertension, and a serum creatinine level above the median value were predictive. In further log rank analyses probands dying during the first years, (e.g. the first 2 years) were removed from the calculations. The prognostic value of the above-mentioned factors diminished with time. In a Cox Regression analysis we found that the predictive value of urinary albumin excretion rate to mortality had disappeared when subjects who had died during the first 5 years were removed from the analysis, whereas HDL in the diabetic patients and blood pressure and serum creatinine in non-diabetic subjects were still of significant predictive value. We therefore conclude that urinary albumin excretion rate is a more short-term predictor of mortality than previously thought, in contrast to HDL, hypertension and serum creatinine.     

Human somatostatin receptor genes: localization of SSTR5 to human chromosome 20p11.2

The gene encoding the somatostatin receptor subtype designated as SSTR5 was mapped to human chromosome 20p11.2 by using fluorescence in situ hybridization to metaphase chromosomes. Fluorescence in situ hybridization using a probe for SSTR5 in combination with probes for neuroendocrine convertase-2 (NEC2), thrombomodulin (THBD), and brain glycogen phosphorylase (PYGB) established a physical order for these loci of 20pter-NEC2-SSTR5-THBD-PYGB-cen.     

Studies of the use of L-leucyl-L-leucine methyl ester in canine allogeneic marrow transplantation

L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) is a lysosomotropic agent that selectively kills cytotoxic T cells and their precursors, natural killer cells, and monocytes but not helper T cells or other cells of hematopoietic origin. In this study, the effects of treatment of bone marrow and peripheral blood buffy coat with Leu-Leu-OMe on the outcome of allogeneic marrow transplantation were studied in several canine models. Whereas incubation of autologous marrow with Leu-Leu-OMe had no adverse effects on subsequent engraftment, incubation of marrow from dog leukocyte antigen (DLA)-identical littermates resulted in a high rate of graft failure. Previous studies have demonstrated that the addition of peripheral blood buffy coat allows engraftment of unrelated DLA-nonidentical marrow, and in this study we found that incubation of buffy coat with Leu-Leu-OMe did not alter this graft promoting effect. In a final experiment it was demonstrated that incubation of both marrow and peripheral blood buffy coat did not prevent the development of graft-versus-host disease in recipients of marrow from DLA-haploidentical littermates. In considering the eventual application of Leu-Leu-OMe in the clinic, these results are less encouraging than those previously reported using murine models.     

Comparison of four purification methods for the production of immunoglobulins from eggs laid by hens immunized with an enterotoxigenic E. coli strain

Calpain and its endogenous inhibitor, calpastatin, were isolated from erythrocytes of various mammals and their properties were compared. It has been widely believed that mammalian erythrocytes contain only mu-calpain. However, rat and human erythrocytes were found to contain two species of calpain, identified as mu-calpain and m-calpain from their elution positions on DEAE-cellulose column chromatography and their Ca(2+)-requirements. Thus, it is apparent that rat and human erythrocytes contain not only mu-calpain, but m-calpain as well. On the other hand, rabbit erythrocytes contain only mu-calpain. Western blot analysis showed that human and rabbit erythrocytes contain predominantly 70-kDa calpastatin (erythrocyte-type), but unnegligible amounts of 110-kDa calpastatin (tissue-type) are also present. Rat erythrocytes were shown to contain a calpastatin with a molecular mass of approx. 100 kDa almost exclusively; this molecular mass was in perfect coincidence with the mass of the calpastatin in rat lung. These results strongly suggest that rat erythrocytes contain a tissue-type calpastatin. No essential change in the calpain/calpastatin system during maturation of rabbit reticulocytes into mature erythrocytes was observed.     

A preliminary assessment of the efficacy of anticancer measures in malignant stomach neoplasms

Three cases of erosive pustular dermatosis of the scalp are reported. In all patients the dermatosis was characterized by pustular, erosive, and crusted lesions; in addition, two patients had areas of scarring alopecia. The results of laboratory tests, bacteriologic and mycologic investigations, and histopathologic examination were nondiagnostic. Although erosive pustular dermatosis of the scalp is characterized by a nonpathognomonic clinical and histopathologic picture, it probably represents a disease entity.