Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries

Summary Lipoprotein(a), as an atherogenic particle, represents an independent risk factor for coronary heart disease. In the present study the morphological distribution of apoprotein (a) and apoprotein B within the arterial wall is described. Apoprotein B, a constituent of very low-density lipoprotein, low-density lipoprotein and lipoprotein(a) has previously been demonstrated in atheromatous lesions. Lipoprotein(a) possesses an additional protein, designated apoprotein (a). Autopsy material (n=74) from the left coronary artery and from the thoracic aorta has been examined by means of immunohistochemistry and both apoprotein (a) and apoprotein B were detected, primarily associated with the extracellular matrix and accumulating in lesions in the arterial wall. The staining pattern for both antigens was almost always found to be congruent, suggesting that the detection of (a)-antigen has to be attributed at least in part to the presence of lipoprotein(a). It is concluded that both low-density lipoprotein and lipoprotein(a) have an important role in the pathogenesis of atherosclerosis.     

Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months

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Optimization of 3-D hepatocyte culture by controlling the physical and chemical properties of the extra-cellular matrices

Hepatocytes are anchorage-dependent cells sensitive to microenvironment; the control of the physicochemical properties of the extra-cellular matrices may be useful to the maintenance of hepatocyte functions in vitro for various applications. In a microcapsule-based 3-D hepatocyte culture microenvironment, we could control the physical properties of the collagen nano-fibres by fine-tuning the complex-coacervation reaction between methylated collagen and terpolymer of hydroxylethyl methacrylate-methyl methacrylate-methylacrylic acid. The physical properties of the nano-fibres were quantitatively characterized using back-scattering confocal microscopy to help optimize the physical support for hepatocyte functions. We further enhanced the chemical properties of the collagen nano-fibres by incorporating galactose onto collagen, which can specifically interact with the asialoglycoprotein receptor on hepatocytes. By correlating a range of collagen nano-fibres of different physicochemical properties with hepatocyte functions, we have identified a specific combination of methylated and galactosylated collagen nano-fibres optimal for maintaining hepatocyte functions in vitro. A model of how the physical and chemical supports interplay to maintain hepatocyte functions is discussed.     

Light bodies in human pituitary adenomas

Summary Light bodies are large cytoplasmic granules originally described in the gonadotrophic cells of the rat pituitary gland. In order to determine whether similar bodies occur in the human anterior pituitary gland, 89 pituitary adenomas and periadenomatous tissue from 20 cases were examined by transmission electron microscopy. Double membrane bound bodies with filamentous internal structure identical to rodent light bodies were identified in 10 hormone-producing adenomas: 5 PRL, 1 PRL-GH, 2 GH, and 2 ACTH-producing tumours. No light bodies were found in the remaining 79 tumours nor in the pituitary cells in periadenomatous tissue from 20 cases. These results show that some human pituitary adenomas may contain light bodies identical to those seen in gonadotrophs of rat pituitary.Abbreviations PRL prolactin - GH growth hormone - ACTH adenocorticotropic hormone - FSH follicle-stimulating hormone - LH luteinizing hormone     

The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs required for cell division but not cell growth

Plant microtubules are organized into specific cell cycle-dependent arrays that have been implicated in diverse cellular processes, including cell division and organized cell expansion. Mutations in four Arabidopsis genes collectively called the PILZ group result in lethal embryos that consist of one or a few grossly enlarged cells. The mutant embryos lack microtubules but not actin filaments. Whereas the cytokinesis-specific syntaxin KNOLLE is not localized properly, trafficking of the putative auxin efflux carrier PIN1 to the plasma membrane is normal. The four PILZ group genes were isolated by map-based cloning and are shown to encode orthologs of mammalian tubulin-folding cofactors (TFCs) C, D, and E, and associated small G-protein Arl2 that mediate the formation of alpha/beta-tubulin heterodimers in vitro. The TFC C ortholog, PORCINO, was detected in cytosolic protein complexes and did not colocalize with microtubules. Another gene with a related, although weaker, embryo-lethal phenotype, KIESEL, was shown to encode a TFC A ortholog. Our genetic ablation of microtubules shows their requirement in cell division and vesicle trafficking during cytokinesis, whereas cell growth is mediated by microtubule-independent vesicle trafficking to the plasma membrane during interphase.     

Prolongation of small bowel allograft survival with a sequential therapy consisting of a synthetic MHC class II peptide and temporarily low-dose cyclosporine A

It has been extensively documented the role of the indirect pathway of allorecognition in allograft rejection. However, recent data demonstrate that the manipulation of this pathway could be also sufficient to promote prolongation of allograft survival. In the present study we evaluated the effect of preoperative immunization with the WF-specific MHC class II peptides RT1.D2 and RT1.B2 in combination with low-dose CsA from days 0 to 7 (5 mg/kg/day) and from days 8 to 30 (1 mg/kg/day) after WF small bowel transplantation. Seven days before and on the day of transplantation, LEW recipients were immunized with the two WF MHC class II peptides RT1.B2 and RT1.D2. The CsA monotherapy induced an allograft survival of 49.3 +/- 6.1 days. MHC class II peptide immunization had a limited effect on allograft survival for RT1.D2 (47.1 +/- 3.8 days) and induced prolongation of allograft survival for RT1.B2 (73.6 +/- 34.6 days). This effect seems to be based on the absence or silence of RT1.B2-reactive T cells and rejection seems to be correlated with the presence of RT1.B2-specific T cells in the late phase. Therefore, the combination of RT1.B2 with low-dose CsA shifts the immunological response and protects small bowel allograft rejection.     

Enhanced MYCN expression and lsochromosome 17q in pineoblastoma cell lines

We have established two cell lines, PER-452 and PER-453, from an 8-month-old girl with an extensive pineoblastoma. Characterization of these lines revealed that the proto-oncogenes MYC and MYCN were not amplified, but both cell lines showed MYCN expression comparable to a cell line with 200-fold MYCN amplification. Both cell lines contained an i( 17q). These results support the concept that pineoblastomas belong to a larger group of primitive neuroectodermal tumors of the central nervous system. These two cell lines provide a unique opportunity to investigate the molecular genetic mechanisms underlying these neoplasms further. Genes Chrom Cancer 9:129-135 (1994).© 1994 Wiley-Liss, Inc.     

A case of imported paracoccidioidomycosis: an awkward infection in The Netherlands.

Paracoccidioidomycosis is an important endemic mycosis in South America. In Europe the disease is very rare and only found as infections in travelers to Latin America. We report here the first case encountered in the Netherlands for which the appropriate diagnosis was not attained for several months. A Dutch 60-year-old man presented with a painful ulceration in the buccal mandibular vestibular mucosa of three months duration. While his medical history was uneventful, he had worked, until 8 years prior to his presentation, as a carpenter for 25 years in the jungles of Peru and Ecuador. An aberrant chest radiograph, CT-scan of the lungs and increased erythrocyte sedimentation rate were suggestive of sarcoidosis or a bronchiolitis obliterans organizing pneumonia. There was no improvement in the patient's symptoms despite the use of budesonide and prednisone medication, as well as tuberculosis prophylaxis with isoniazide and rifampicin, and local use of miconazole. Quite to the contrary, as an irritated, irregular hyperemic mucosa and gingiva with ulceration were noticed during this period of time. These precipitated an incisional biopsy through which a mixed inflammatory cellular infiltrate and large yeast cells were found on histopathologic examination. Based on the patient's travel history and the multiple budding yeastlike cells revealed in the biopsy tissue, the diagnosis of paracoccidioidomycosis was finally made. This was supported by the isolation of Paracoccidioides brasiliensis in culture. Antimycotic oral therapy with itraconazole was started and continued for 15 months. At two and five year follow-ups, the patient was asymptomatic. In Europe, it may be expected that diseases that are endemic in other areas will be seen more frequently in countries where the diseases are not routinely encountered. It is most likely that the use of corticosteroid medication, with its inherent immunosuppressive effect, resulted in the reactivation of an infection acquired many years before in Latin America. The etiologic agent then disseminated from the initial focal point to cause the ensuing oral mucous membrane lesions. The importance of the patient's prolonged residence in Latin America was overlooked. The very long latency of endemic mycoses emphasizes the need for a meticulous history which should include not only recent trips, but also past residence in foreign countries.     

Clinical and epidemiological aspects of human bocavirus infection

Human bocavirus was recently described as a novel member of the Parvoviridae to infect humans. Based on accumulating clinical and epidemiological data the virus is currently being associated with respiratory infections in young children and infants and is furthermore discussed as causative agent of gastrointestinal illness.