Pathogenesis of Mucocutaneous Lesions in Behçet's Disease

Behcet's disease (BD) is characterized by recurrent oral aphthae, skin lesions, eye lesions, and genital ulceration. To determine the pathogenesis of BD, we performed histological and immunohistochemical studies of these mucocutaneous lesions, an assay of neutrophil activity, and HLA typing. Dense dermal or subcutaneous infiltrations of polymorphonuclear cells (PMN) without leukocytoclastic vasculitis were found in 28 of 57 lesions. Immunohistochemically, deposits of C3 on the vessels were found in 12 of 31 lesions. Deposits of immunoglobulin were not found except for one of IgM. C3 deposits and PMN infiltrations were significantly related (p<0.05). PMN activity by polarization was enhanced; however, the results did not show a significant relationship with the PMN infiltrations or the C3 deposits. The incidence of HLA-B51 was significantly high in BD, but no significant relationship was found between HLA-B51 and the results of other examinations. These results suggest that the pathogenesis of BD lesions differs from that of collagen diseases and that C3 deposits on the vessels may play an important role in the development of mucocutaneous lesions where PMN have mainly infiltrated.     

Diversity in DNA rearrangements and in RNA expressions of immunoglobulin gene on common variable immunodeficiency.

Six heterogeneous common variable immunodeficiency (CVID) patients were analysed for germ-line DNA, DNA rearrangements, and RNA expressions of immunoglobulin (Ig) gene by Southern or northern blotting using appropriate probes. We detected no polymorphism in neutrophil DNA hybridized to a C mu and a C gamma probe. In three patients, both serum Ig and Ig-bearing cells were scarcely detected, and by northern hybridization methods, neither mu mRNA, gamma mRNA, alpha mRNA nor kappa mRNA was detected. However, one Epstein-Barr virus-transformed B lymphoblastoid cell line (LCL) of these three patients was different from the germ line in the region of JH, C gamma, and C kappa, and expressed mu mRNA at a higher level. The B cell defects of these three patients lay on the B cell maturation stage similar to X-linked agammaglobulinaemia (XLA). In two others among the six CVID patients, serum IgM and IgM-bearing cells were detected to a certain degree, and by northern hybridization, mu mRNA was detected at a lower level, but neither mu mRNA, alpha mRNA, nor kappa mRNA was detected. One LCL of these two patients could express mu mRNA at the normal level. In the last patient, the serum IgM was normal, serum IgG and IgA were somewhat low, Ig-bearing cells were normal, mu mRNA and kappa mRNA were detected at the normal level, and gamma mRNA and alpha mRNA were detected at a lower level. The defect of this patient affected the class switch stage. These results showed that primary B cell defects in CVID occurred at several B cell differentiation stages which could be classified by expression of the Ig gene, and at the degree of clonal diversity in the B cell repertoire. Furthermore, this study provides support for the idea that the CVID defect is related to a more generalized cellular function, such as regulating the proliferation and/or clonal expansion of cells of the B lymphoid lineage.     

An experimental study on direct revascularization of bronchial circulation by microvascular anastomosis.

The effects of direct revascularization of the bronchial artery after bronchoplasty were estimated by laser Doppler velocimetry and india ink injection in dogs. Bronchoplastic surgery at the right main bronchus was performed in all dogs, and the bronchial artery was reconstructed using the internal thoracic artery in the reconstruction group. The mucosal blood flow was measured at the distal side of the anastomosis. India ink was injected into the aorta in the nonreconstruction group and into the internal thoracic artery in the reconstruction group. The peripheral blood flow had diminished immediately after surgeries to 59% of the baseline value and took 14 days to recover to the baseline value in the nonreconstruction group. However, in the reconstruction group, the blood flow recovered at once to 78% of the baseline value and had returned to that value in 5 days. Statistically significant differences were noted between the groups from just after operation to day 7. India ink data confirmed these findings. In the nonreconstruction group, no ink was observed in the peripheral bronchial vessels on day 3; it was noted in part of the vessels on day 7 and in most on day 14. On the other hand, a relatively large number of vessels were stained just after operation in the reconstruction group. Thus reconstruction of the bronchial artery by means of the anastomosis with the internal thoracic artery can be said to be a useful and effective method for preventing airway ischemia.     

Metabolism of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in blood--mainly in vitro]

Metabolism of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in blood was studied mainly in vitro. When 99mTc-ECD was mixed with blood taken from 12 subjects, the octanol extraction ratio of ECD (y) decreased rapidly and the octanol extraction ratio-time profile well fitted a monoexponential curve (y = Ae-kt/1000, A, k: constant, t: time after mixing). The k value and hematocrit (Ht) were significantly correlated (k = 0.376Ht-3.27, r = 0.897, p less than 0.001), therefore, it was suggested that the majority of the enzyme which dissolves ECD exists in red blood cells. When ECD was mixed with blood, there were more hydrophilic products of ECD in plasma than those generated by the enzyme in plasma. In vivo input function of 99mTc-ECD was calculated by arterial blood sampling and octanol extraction. The duration of effective input was relatively short, which was attributed to rapid decrease of octanol extraction ratio in vivo.     

Effects of inhibitors of protein kinase C and Na+/H+ exchange on alpha 1-adrenoceptor-mediated inotropic responses in the rat left ventricular papillary muscle.

1. Alpha 1-adrenoceptor stimulation of rat left ventricular papillary muscle produced a triphasic inotropic response: an initial transient positive inotropic effect (PIE) followed by a transient negative inotropic effect (NIE) and a sustained PIE. 2. The protein kinase C inhibitor, staurosporine, at concentrations ranging from 30 nM to 100 nM inhibited the sustained PIE, but had no significant effect on the transient PIE and NIE. 3. H-7, 1-(5-isoquinoline sulphonyl)-2-methylpiperazine, a less specific inhibitor of protein kinase C than staurosporine, at a concentration of 100 microM inhibited both the transient NIE and the sustained PIE without affecting the transient PIE. 4. Amiloride, an inhibitor of Na+/H+ exchange, at concentrations ranging from 0.1 mM to 1 mM inhibited the sustained PIE and, at higher concentrations, also inhibited the transient NIE. 5. An amiloride analogue, 5-(N-methyl-N-isobutyl)amiloride (MIBA), inhibited only the sustained PIE with an IC50 of 0.3 microM which is approximately two orders of magnitude lower than amiloride. 6. The receptor-linked stimulation of Na+/H+ exchange through protein kinase C activation may be a mechanism for alpha 1-adrenoceptor-mediated sustained PIE.     

ELISA using monoclonal antibody to human serum arylesterase.

ELISA for determining arylesterase content in human serum has been developed by the one-step sandwich method using 2 monoclonal antibodies. While the content of arylesterase in healthy adults was 81 +/- 25 mg/l, a decrease was observed in patients with liver cirrhosis, where the mean +/- SD was 37 +/- 7 mg/l. ELISA of human serum arylesterase correlated with the activity determined by a specific substrate assay we devised recently.     

Toluene vapor exposure and urinary excretion of hippuric acid among workers in China.

A factory survey was conducted in three provinces in China from 1985 to 1989. The time-weighted average toluene concentrations in breathing zone air were monitored by diffusive sampling, whereas hippuric acid (HA) concentrations in shift-end urine samples were measured by high performance liquid chromatography (HPLC). Exposed workers (456 men and women) were those for whom toluene (up to 548 ppm toluene) accounted for greater than or equal to 90% of total exposure (by vapor concentration in ppm), whereas 517 nonexposed controls were recruited from the same factories or from factories of the same region. There was a linear correlation between the intensity of toluene exposure and HA concentration in the shift-end urine. Comparison of the results with findings in the literature shows that the toluene-induced increase in urinary HA concentration among workers in China is significantly smaller than the published values, whereas HA concentrations in urine samples from nonexposed controls are comparable to the levels previously reported.