Effect of IL-4 deletion on cardiac allograft survival in the BALB/c to 129Sv x C57BL/6 strain combination

Calcified brain metastases are rare. They are unique or multiple. The primary site is lung, breast, gastro-intestinal tract, uterine cervix, bone or may be unidentified. It corresponds pathologically to an adenocarcinoma, a sarcoma or to a squamous cell carcinoma. We report a case of multiple calcified brain metastases discovered before primary tumour (bronchial adenocarcinoma), raising the problem of differential diagnosis resolved by stereotaxic brain biopsy.     

Molecular forms of acetylcholinesterase in dystrophic (mdx) mouse tissues

We analyzed the activity of acetylcholinesterase (AChE) and its molecular forms in the tissues of normal and dystrophic (mdx) mice, at different developmental stages. We studied the brain, the heart and the serum, in addition to four predominantly fast-twitch muscles (tibialis, plantaris, gastrocnemius and extensor digitorum longus (EDL)) and the slow-twitch, soleus muscle. We found no difference between mdx and control mice in the AChE activity of the brain and the heart. The skeletal muscles affected by the disease undergo active degeneration counterbalanced by regeneration between 3 and 14 weeks after birth. The distribution of AChE patches associated with neuromuscular junctions was abnormally scattered in mdx muscles, and in some cases (tibialis and soleus), the number of endplates was more than twice that of normal muscles. There were only minor differences in the concentration and pattern of AChE molecular forms during the acute phase of muscle degeneration and regeneration. After this period, however, we observed a marked deficit in the membrane-bound G4 molecular form of AChE in adult mdx tibialis, gastrocnemius and EDL but not in the plantaris or in the soleus, as compared with their normal counterparts. Whereas the amount of AChE markedly decreased in the serum of normal mice during the first weeks of life, it remained essentially unchanged in the serum of mdx mice. It is likely that this excess of AChE activity in serum originates from the muscles. A deficit in muscle G4 was also reported in other forms of muscular dystrophy in the mouse and chicken. Since it is not correlated to the acute phase of the disease in mdx and also occurs in genetically different dystrophies, it probably represents a secondary effect of the dystrophy.     

Acute monocytic leukaemia in a HIV-seropositive man

Individuals infected with the human immunodeficiency virus (HIV) have been reported to develop a number of malignant neoplasms. We recently treated an HIV patient who had acute monocytic leukaemia which was first evident in the skin. To our knowledge, this is the first report of a case of acute monocytic leukaemia occurring in a HIV-infected person.     

Cellular and chemical mediators of type 1 hypersensitivity in calves infected with Ostertagia ostertagi: histamine, prostaglandin D2, prostaglandin E2 and leukotriene C4

Plasma histamine, prostaglandin E2 (PG) D2, PGE2, and leukotriene (LT) C4 levels were determined in 26 Holstein steers before and after natural or experimental infection with Ostertagia ostertagi. Post-infection abomasal lymph was also assayed for PGD2, PGE2, and LTC4. Histamine determinations were performed on abomasal tissue from three locations. Results showed that: (1) tissue histamine levels increased in steers with type 2 ostertagiosis, (2) lymphatic PGD2 and PGE2 levels were increased, probably as a result of macrophage activity, (3) lymphatic LTC4 levels increased in steers with type 1 ostertagiosis, and were correlated with tissue eosinophilia, and (4) plasma levels of PGD2, PGE2, LTC4 and histamine were not useful for predicting worm burdens. These findings suggest a functional role for eosinophils and mast cells in the pathophysiology of ostertagiosis, through mediation of a type 1 hypersensitivity reaction.     

Patients in Norwegian hospitals. Length of stay and patterns of use

All 633,987 periods of admission to Norwegian general hospitals in 1991 were analyzed. The length of stay increases considerably with the patient's age. 80-year old patients stay three times as long in hospital as five-year old patients. The typical surgical patient requires 56% more resources than the typical medical patient. For surgical patients, the mean length of stay was 7.2 days, and for medical patients it was 6.8 days. Patients in the age group 70-79 years require almost twice as much resources as the youngest patients. Patients up to the age of 65 who live in a municipality where there is a hospital stay in hospital just as long as corresponding patients from municipalities without a hospital. For older patients there are significant differences in length of stay for these two categories of patients. The discharge rate for men of 70 years and older is significantly higher than the rate for women in the same age group, but the women stay longer in hospital.     

N-myc suppresses major histocompatibility complex class I gene expression through down-regulation of the p50 subunit of NF-kappa B

In neuroblastoma, N-myc suppresses the expression of major histocompatibility complex (MHC) Class I antigens by reducing the binding of a nuclear factor to the enhancer-A element in the MHC Class I gene promoter. We show here that the p50 subunit of NF-kappa B is part of this complex and that expression of p50 mRNA is suppressed by N-myc. Transfection of a p50 expression vector in neuroblastoma cells that express N-myc at a high level leads to restoration of factor binding to the MHC Class I gene enhancer, restores enhancer activity and leads to re-expression of MHC Class I antigens at the cell surface. These data indicate that the p50 subunit of NF-kappa B is involved in the regulation of MHC Class I antigen expression and that N-myc down-regulates MHC Class I gene expression primarily through suppression of p50 expression.     

Apical orientation of the microtubule organizing center and associated gamma-tubulin during the polarization of the retinal pigment epithelium in vivo

Simple epithelial cells express a morphological and functional polarity along their apical-to-basal axis. During the development of epithelia, a unique reorganization of microtubule arrays is thought to play a fundamental role in the establishment of cell polarity. To begin to understand this process in vivo, we have determined the distribution of gamma-tubulin within developing chicken retinal pigment epithelium (RPE). gamma-Tubulin is a recently discovered centrosomal protein that plays a role in nucleating microtubule growth from the centrosome. Although the RPE monolayer becomes established during embryonic Day 3, cell polarity gradually develops and matures over the next 10-13 days. Our studies reveal that gamma-tubulin is located in a distinct focus subjacent to the apical membrane by embryonic Day 3, the beginning of the polarization process. Using primary cell cultures, we examined the relationship between the establishment of junctional complexes and the reorganization of microtubule arrays. Despite the recovery of junctional complexes and a transepithelial electrical resistance, cultured cells failed to relocate gamma-tubulin foci to a position subjacent to the apical membrane. Rather, these foci remained in the juxtanuclear region. These data indicate that the rearrangement of unique, epithelial microtubule arrays requires more than cell-cell and cell-basement membrane interactions.     

Selection of an anti-IGF-1 Fab from a Fab phage library created by mutagenesis of multiple CDR loops

Diverse Fab libraries containing 2-3 x 10(8) members were generated by randomizing amino acid residues within four of the six complementarity determining regions of a humanized version of an anti-HER-2 Ab (hu4D5). These libraries were subsequently displayed on the surface of the filamentous bacteriophage M13 and selected for binding to three proteins: CD4, insulin-like growth factor 1 (IGF-1), and tissue plasminogen activator. An Fab-bacteriophage was isolated that showed specific binding to IGF-1. The affinity of this Fab was determined to be 3.5 microM.     

Nitric oxide-mediated changes in vascular reactivity in pregnancy in spontaneously hypertensive rats

1. To examine the mechanisms which may account for pregnancy-induced vasodilatation in spontaneously hypertensive rats (SHR), we have investigated the changes in vascular reactivity and the effects of endothelial nitric oxide (NO) inhibition in the in situ blood-perfused, mesenteric resistance vessels of 18-20 day pregnant SHR. The effects of NG-nitro-L-arginine (L-NOARG) were compared in pregnant and nonpregnant SHR and gestation matched normotensive Wistar-Kyoto (WKY) rats. 2. Intra-arterial mean blood pressures (MBP) were similar in pregnant and nonpregnant SHR. Basal perfusion pressures (BPP) were decreased in pregnant compared with nonpregnant SHR. Pregnant WKY had lower MBP and BPP than either pregnant or nonpregnant SHR. 3. Vasoconstrictor responses to electrical stimulation (ES) and intra-arterial noradrenaline (NA) were decreased in pregnant compared with nonpregnant SHR. These responses were still greater in pregnant SHR when compared with pregnant WKY. Vascular reactivity to angiotensin II (AII) in pregnant SHR was reduced to a similar level to that in pregnant WKY. 4. L-NOARG (5 mg kg-1, i.v.), an inhibitor of nitric oxide synthase, increased MBP and BPP in all groups. After L-NOARG, BPP were equalized between pregnant and nonpregnant SHR. Pregnant WKY still showed lower MBP and BPP than SHR groups. 5. L-NOARG potentiated vascular responses to ES, NA and AII in all groups. The blunted vascular responses to NA and ES were normalized and the reactivity to AII was only partially reversed in pregnant SHR compared with nonpregnant SHR. Pregnant WKY still had much lower vascular responses to ES and NA than either pregnant or nonpregnant SHR. L-NOARG enhanced vascular responses to All to a greater extent in pregnant SHR than in pregnant WKY.6. These results demonstrate that blunted responses to NA and ES were NO-dependent, while diminished reactivity to AII was only partially dependent on NO in the in situ blood perfused mesenteric resistance vessels of pregnant SHR.7. The present results in pregnant SHR differ from our previous finding with pregnant normotensive WKY, in which blunted responses to NA, but not to ES, were equalized by L-NOARG. Pregnancy induced vasodilatation in hypertensive rats appears to be more dependent on endothelial NO than in normotensive WKY. A defect of the endothelial NO generating pathway which promotes vasodilatation in pregnancy may contribute to the predisposition of women with essential hypertension to develop pre-eclampsia.