Plasminogen activation in plasma of patients with systemic lupus erythematosus

Summary We measured ₂-plasmin inhibitor-plasmin complexes (PI-PC) in plasma of patients with systemic lupus erythematosus (SLE) to examine the plasminogen activation in SLE. The plasma PI-PC level in 23 patients with SLE was significantly higher than that in 18 normal subjects (P<0.001) and the SLE patients with nephrotic syndrome had higher plasma PI-PC levels than those without nephrotic syndrome (P<0.01). In addition, the plasma PI-PC level was significantly correlated with the level of plasma C3 breakdown products (iC3b/C3dg) in the patients with SLE (r=0.53, P<0.01). These results suggest that plasminogen is activated in plasma of patients with SLE and that the plasminogen activation may be associated with the activation of complement in SLE.     

The gastrointestinal prokinetic benzamide derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurons

Summary We have previously shown that a non-classical 5-hydroxytryptamine (5-HT₄) receptor mediates the stimulation of adenylate cyclase activity in mouse embryo colliculi neurons in primary culture. The pharmacological characteristics of this receptor exclude the possibility that it belongs to the known 5-HT₁, 5-HT₂ or 5-HT₃ receptor types. Here we report that this 5-HT receptor can be stimulated by 4-amino-5-chloro-2-methoxy substituted benzamide derivatives. All these compounds have been reported to be potent stimulants of gastrointestinal motility and some of them are 5-HT₃ receptor antagonists. The rank order of potency of these substituted benzamide derivatives in stimulating cAMP formation was: cisapride > BRL 24924 > 5-HT > zacopride > BRL 20627 > metoclopramide. The non-additivity of benzamide and 5-HT activities suggests that 5-HT and the substituted benzamide derivatives act on the same receptor. Only ICS 205930, a recognized 5-HT₃ receptor antagonist, competitively antagonized the stimulatory effect of cisapride, zacopride and BRL 24924. However, its pK _i (6–6.3) for this new receptor was very different from its pK _i for 5-HT₃ receptors (pK _i = 8 –10). Other selective 5-HT₃ receptor antagonists with an indole group (BRL 43694 and GR 38032F), with a benzoate group (cocaïne, MDL 72222) or with a piperazine group (quipazine) were ineffective in reversing the stimulatory effect of benzamide derivatives. Exposure of neuronal cells to potent agonists at this receptor such as BRL 24924 rapidly reduces its capacity to stimulate cAMP production. For example, a preincubation of 10 min with BRL 24924 (100 mol/l) reduced by 42% the ability of 5-HT to stimulate cAMP production. Cross-desensitization occurs between the effects of 5-HT and benzamides. The unique pharmacology of these nonclassical 5-HT receptors that we propose to call 5-HT₄ is very close and even identical to the pharmacology of the high affinity 5-HT receptors involved in the indirect stimulation of smooth muscle in the guinea pig ileum. These receptors are different from the 5-HT₃ receptors also present in guinea pig ileum.Send offprint requests to A. Dumuis at the above address     

Concomitant translocation of Puralpha with its binding proteins (PurBPs) from nuclei to cytoplasm during neuronal development

Two Puralpha-binding proteins (PurBPs) were found in nuclear extract from mouse brain during P4-P10 by the overlay assay. At P14, they were decreased significantly in nuclear extract and increased in the S3 fraction, indicating their dynamic translocation during development. Western blot analysis also demonstrated concomitant translocation of Puralpha with the PurBPs during P7-P14, when neuronal circuit proceeds. Immunocytochemical study with cultured hippocampal neurons from rat E18 confirmed that nuclear Puralpha was translocated to cytoplasm after plating for 7-14 days. These results suggest that spatiotemporal translocation of Puralpha with the PurBPs from nuclei to cytoplasm has a crucial role in neuronal development.     

A novel t(2;6)(p12;q23) appearing during transformation of follicular lymphoma with t(18;22)(q21;q11) to diffuse large cell lymphoma

Follicular lymphoma is characterized genetically by t(14;18)(q32;q21), whereas t(18;22)(q21;q11), a rare variant form of t(14;18), has been preferentially observed in chronic lymphocytic leukemia (CLL). We describe here an unusual case of follicular lymphoma with a t(18;22)(q21;q11), that progressed to diffuse large cell lymphoma with a novel t(2;6)(p12;q23). Spectral karyotyping revealed that add(2)(p12) and add(6)(q23) were derived from a t(2;6)(p12;q23). Fluorescence in situ hybridization analysis confirmed rearrangements of the BCL2 gene at 18q21 and the BCL6 gene at 3q27. Our results indicate that a reciprocal translocation involving 6q23 could be implicated in the progression of follicular lymphoma and that t(18;22) may have a specific role in the pathogenesis of follicular lymphoma as well as CLL.     

Influence of ascending noradrenergic fibers on the neurotensin-like immunoreactive perikarya and evidence of direct projection of ascending neurotensin-like immunoreactive fibers in the rat central nucleus of the amygdala

The influence of ascending noradrenergic neuronal input on the neurotensin (NT)-like immunoreactive neuronal perikarya located in the dorsal part of the central nucleus of the amygdala (CNA) was examined using fluorescence histochemistry and peroxidase-antiperoxidase (PAP) immunocytochemistry. Unilateral hemitransection of the ascending noradrenergic pathway by injection of 6-hydroxydopamine into the caudal mesencephalon just rostral to the locus coeruleus caused a marked depletion of immunoreactivity in NT-like immunoreactive neuronal perikarya in the CNA. Ascending noradrenergic neuronal input, therefore, is considered to facilitate production of NT-like immunoreactive substances in neuronal perikarya and to influence on the functional role of the amygdaloid complex. In addition, we obtained evidence of unilateral direct ascending projections of NT-like immunoreactive neurons into the CNA since the disappearance of NT-like immunoreactive processes occurred mainly in the ventral part of the CNA after surgical hemitransection of the ascending neuronal pathway that interrupts the ascending NT-like immunoreactive pathway arising from the neurons in the brain stem.     

Pathogenic capacity of proteases from Serratia marcescens and Pseudomonas aeruginosa and their suppression by chicken egg white ovomacroglobulin.

The pathogenicities of three proteases from Serratia marcescens, two proteases from Pseudomonas aeruginosa, and one thermolysin from Bacillus stearothermophilus were examined. All proteases tested caused acute liquefactive necrosis of the cornea and descemetocele formation in guinea pig eyes after intrastromal injection, with the exception of the 60-kilodalton protease from S. marcescens, which produced only an opaque lesion. When injected into guinea pig skin, the protease also enhanced vascular permeability, which was followed by edema formation. The permeability-enhancing activity of the proteases increased in parallel with the concentration of the enzymes. When tested in vitro for its effect on these bacterial proteases, chicken egg white ovomacroglobulin (ovoM) inhibited the enzymatic activity of all the proteases after a short incubation period at an enzyme/inhibitor ratio (molar) of 1:1 to 1:4 or at a lower concentration after a longer incubation period. Such treatment of the proteases with chicken egg white ovoM before injection intrastromally into the eyes or intradermally into the clipped flanks of guinea pigs protected the cornea from destruction or completely prevented the permeability reaction and edema formation. No inhibitory effects of plasma protease inhibitors against these bacterial proteases were noted. Since the proteases are critical in the pathogenic processes caused by the bacteria, these results suggest a beneficial effect of ovoM against bacterial infections.     

Study on effects of life review activities on the quality of life of the elderly: a randomized controlled trial

BACKGROUND: The objective of this study was to evaluate the mid-term efficacy of life review activities on the quality of life (QOL) of the elderly by conducting a randomized controlled trial, and to identify the factors that should be taken into consideration when conducting life review activities. METHODS: Written consent was obtained from 80 of the 97 eligible elderly persons. After randomly assigning them to two groups, an intervention group and a control group, group life review activities were conducted in the intervention group and discussion activities about health were conducted in the control group. In both the intervention group and the control group, life satisfaction, self-esteem, depression, and hopelessness were evaluated using self-rating scales at three points: at baseline, immediately after completion of the 8 weeks of sessions, and 3 months after completion of the intervention. RESULTS: Repeated measures analysis of covariance showed significant differences between the two groups in the changes in scores for depression (p = 0.04) and hopelessness (p = 0.04). Regarding the factors that were associated with depression and hopelessness, 3 months after completion of the intervention, depression and hopelessness of a more severe nature at baseline and having greater unresolved conflicts in the past were extracted by multiple regression analysis. CONCLUSIONS: The results suggested that group life review activities have a role in assisting the developmental stage of old age and supporting mental health, and have mid- to long-term effectiveness in maintaining and improving the QOL of the elderly.     

Serological study of an allergic agranulocytosis due to noramidopyrine

An allergic agranulocytosis induced by amidopyrine and triggered by noramidopyrine was studied. Leucoagglutinating and leucocytotoxic antibody, active only in the presence of the drug, was demonstrated. The antibody was stable, giving a titre from 1·34 to 1·62 and was present in the IgM (19S globulin) and in the IgG (7S globulin) serum fractions. The site of drug fixation was studied by use of iodoantipyrine labelled with ¹³¹I; a stable fixation was demonstrated on to the IgM and IgG globulins. Special emphasis is given to cross-reaction with compounds related to amidopyrine.     

HeLa cell invasiveness and O antigen of Shigella flexneri as separate and prerequisite attributes of virulence to evoke keratoconjunctivitis in guinea pigs.

Many rough mutants selected from isogenic smooth virulent and avirulent strains of Shigella flexneri were examined for virulence, using tissue culture infection and Sereny tests. Many of the rough mutants isolated from a virulent smooth strain were capable of penetrating tissue culture cells but incapable of producing a positive Sereny test. In contrast, we could not obtain from smooth avirulent strains any rough mutants capable of penetrating HeLa cells. Chemical analysis of lipopolysaccharide of some representative rough strains showed several patterns of sugar composition with a range of from Ra to Re chemotypes. There was no correlation between HeLa cell invasiveness and chemotypes of lipopolysaccharides, thus indicating little significance of oligosaccharides of the rough core as well as O antigens in the ability of S. flexneri to penetrate HeLa cells. When these invasive rough strains were given O antigen genes from a smooth avirulent Shigella Hfr strain, most of the transconjugants that expressed O antigens regained the ability to evoke keratoconjunctivitis in guinea pigs. We also examined the chromosomal loci of HeLa cell invasion by transferring carbohydrate fermentation genes of Escherichia coli K-12 Hfr and found two chromosomal loci, the rha and lac-gal regions, which control the ability to penetrate HeLa cells. These results suggested that O antigens and ability to penetrate tissue culture cells are independent and prerequisite attributes of virulence in Shigella flexneri to evoke keratoconjunctivitis in guinea pigs.     

HLA haplotype study of 53 juvenile insulin-dependent diabetic (I.D.D.) families

Fifty-three families with at least one IDD patient were genotyped for 5 markers of the HLA complex including Bf and DR. In 8 families one of the parents was also affected and in 12 families more than two children were diseased. In total, 76 patients were genotyped. Their haplotypes were compared with those of 106 unrelated controls (the parents of 53 genotyped families).

• 1) 

  Three haplotypes or segments of them (A2, Cw3, B15, BfS, DR4; Aw30, Cw5, B18, BfF I, DR3; and Al, Cw7, B8, BfS, DR3) were found more frequently in IDD patients.
• 2) 

  Measured by the 6 formula, the association of the postulated IDD susceptibility gene was very strong with the D-end of two of these haplotypes: BfF1, DR3 and BfS, DR4. However, the association was weak with the DR3 of the haplotype Al, Cw7, B8, BfS, DR3.
• 3) 

  An excess of HLA-identical affected siblings was found.
• 4) 

  An excess of DR3/DR4 heterozygotes was observed. By contrast, the observed frequency of patients homozygous for DR3 or DR4 was not increased, but even slightly decreased.

The data support a model of inheritance comprising at least two closely linked specifically "diabetic" loci (most of the time marked by B18, BfFl, DR3 and B15, BfS, DR4) and a non-specifically "diabetic" haplotype favouring auto-immunisation (most of the time marked by B8, BfS, DR3). This model is discussed in the light of the presented data and of those of the literature.