ABC proteins: key molecules for lipid homeostasis

Forty-nine ABC protein genes exist on human chromosomes. Eukaryotic ABC proteins were originally recognized as drug efflux pumps involved in the multidrug resistance of cancer cells. However, it is now realized that one of their major physiological roles is cellular lipid transport and homeostasis, and their dysfunction is often associated with human diseases. ABCA1 and ABCA7 mediate the apolipoprotein-dependent formation of a high-density lipoprotein–cholesterol complex. ABCA3 is indispensable for pulmonary surfactant secretion. ABCG5 and ABCG8 are involved in the secretion of plant sterols and cholesterol into bile. However, the primary substrates and mechanism of action of these ABC proteins have not been precisely defined. In this review article, we first describe the general structure and functions of eukaryotic ABC proteins. The current model of ABCA1 functionality is then explained based on studies on a topological model, subcellular localization, apoA-I dependence of HDL formation, functional defects of Tangier disease mutants, and ATP hydrolysis of purified ABCA1. ABCA1 is supposed to function as a transporter of lipids as well as a receptor for apoA-I. ABCA3 is likely involved in accumulating phospholipids and cholesterol in lamellar bodies and in generating multivesicular structures.     

Elevated nasal mucosal G protein levels and histamine receptor affinity in a guinea pig model of nasal hyperresponsiveness

BACKGROUND: Nasal hyperresponsiveness is a common feature of allergic rhinitis, but the underlying mechanisms have yet to be elucidated. The effects of repeated antigen inhalation on the characteristics of histamine H(1) receptors and expression levels of heterotrimeric guanosine 5'-triphosphate-binding proteins in nasal mucosa were investigated to understand the mechanisms of the pathogenesis of nasal hyperresponsiveness in allergic rhinitis. METHODS: Male Hartley guinea pigs were sensitized by the inhalation of dinitrophenylated ovalbumin antigen (10 mg of protein/ml) and repeatedly challenged by inhaling aerosolized dinitrophenylated ovalbumin antigen for 3 weeks. Twenty-four hours after the last antigen inhalation, in vivo nasal responsiveness to histamine was measured. [(3)H]Mepyramine binding assays and immunoblotting for alpha subunits of the G(q) protein were also performed using membrane preparations of isolated nasal mucosae. RESULTS: The histamine-induced increase in intranasal pressure was significantly augmented after repeated antigen challenge, indicating that nasal hyperresponsiveness was achieved. In saturation binding studies, no significant change was observed in the density and antagonist affinity of H(1) receptors in the hyperresponsive animals. On the other hand, the affinity of histamine for high-affinity agonist binding sites in the hyperresponsive group, measured by histamine competition binding studies, was much greater than that in control animals, and these results were affected by guanosine 5'-O-(3-thiotriphosphate) in both groups. Moreover, Galpha(q) levels in nasal mucosal homogenates were significantly increased after repeated antigen challenge. CONCLUSIONS: Elevated G protein levels in nasal mucosa might induce an increased binding affinity of histamine to its receptors, resulting in an augmented nasal response to histamine, that is, nasal hyperresponsiveness, in guinea pigs.     

Four cases of wheat-dependent exercise-induced anaphylaxis with negative gluten cap-rast score]

BACKGROUND: Either omega-5 gliadin or high molecular weight glutenin is known to be a major allergen in wheat-dependent exercise-induced anaphylaxis (WDEIA). It is generally considered that gluten specific IgE score is more reliable than that of wheat specific IgE score for the diagnosis of WDEIA. Our aim was to verify the significance of gluten specific IgE in the diagnosis of WDEIA. METHODS: We evaluated the result of gluten CAP-RAST score and omega-5 gliadin specific IgE score on four WDEIA patients who visited our hospital during the years 2004 and 2005, whose diagnosis were onfirmed by prick tests, immunoblot tests and provocation tests. RESULTS: Contrary to our expectations, all four patients showed negative gluten CAP-RAST scores, however all patient's omega-5 gliadin specific IgE scores were positive. CONCLUSION: Our results suggest that gluten specific CAP-RAST score is unreliable in the diagnosis of WDEIA. On the other hand omega-5 gliadin specific IgE score is possibly a better candidate as a diagnostic tool for WDEIA.     

Strain differences of the light-dark preference in inbred rats

he present study examined strain differences in the light-dark preference among four strains of rats. The test was done in the home-cage situation under 12L:12D cycles. Data from four strains were compared: BN/Kyo, BDIX/Nem, Wistar/Nu, and F344/NSlc. These strains differed in the light-dark preference measured by the ratio of the time spent in the field area of the home cage during the light period. BN/Kyo and BDIX/Nem spent the most time (approx. 23%) in the field during the light period, while F344/NSlc spent the least time (approx. 5%). Wistar/Nu fell between the two (approx. 12%).This study was conducted as partial fulfillment for the master's degree, submitted to Nagoya University by the first author. It was presented at the 47th Annual Conference of the Japanese Society of Animal Psychology.     

Myelin Degeneration in Multiple System Atrophy Detected by Unique Antibodies

A rabbit antiserum (anti-EP), induced against a synthetic peptide corresponding to residues 68 to 86 of guinea pig myelin basic protein, powerfully immunostained abnormal-appearing oligodendrocytic processes and cell bodies in demyelinating areas associated with multiple system atrophy (MSA). However, as we reported previously, the antiserum, which is highly specific for the sequence QDENPVV corresponding to human myelin basic protein residues 82 to 88, failed to recognize any structures in normal human brain. QD-9, a mouse monoclonal antibody raised against human myelin basic protein residues 69 to 88, which also recognizes specifically the epitope QDENPVV, gave the same results as did anti-EP. The unusual epitope recognized by anti-EP/QD-9 antibodies appears to be accessible in areas of myelin degeneration, and the antibodies have been shown to detect such areas in multiple sclerosis and infarcted brains. These antibodies detect myelin degeneration more widely than previous conventional methods. The present study emphasizes the importance of myelin degeneration in the pathogenesis of multiple system atrophy.     

Intracerebroventricular injection of brain natriuretic peptide inhibits vasopressin secretion in conscious rats

The effect of intracerebroventricular (i.c.v.) injection of brain natriuretic peptide (BNP), a novel peptide purified from the porcine brain, on arginine vasopressin (AVP) secretion was studied in conscious, unrestrained rats and was compared with that of atrial natriuretic polypeptide (ANP). I.c.v. administration of BNP (0.01, 0.1 or 1 nmol) significantly inhibited basal AVP secretion and the effect of BNP was comparable to that of ANP. The AVP secretion induced by i.c.v. injection of angiotensin II (0.1 nmol) was significantly suppressed by the pretreatment with BNP (0.1 or 1 nmol). These results suggest that BNP is involved in the central control of AVP secretion either alone or in combination with brain ANP.     

<Emphasis Type="Italic">GPC5</Emphasis> is a possible target for the 13q31-q32 amplification detected in lymphoma cell lines

Comparative genomic hybridization (CGH) analyses have detected gains of copy number on 13q, especially at 13q31-q32, in cell lines and primary cases of various types of lymphoma. Since amplification of chromosomal DNA is one of the mechanisms that can activate tumor-associated genes, and because 13q amplification had been reported in various other types of tumors as well, we attempted to define by fluorescence in situ hybridization (FISH) a common region at 13q31-q32 in which to explore genes that might be targets for the amplification events. Although the commonly amplified region we defined was relatively large (approximately 4 Mb), only one true gene, GPC5, was found there. GPC5 was over-expressed in lymphoma cell lines that had shown amplification, in comparison with those that had not. Our findings suggest that GPC5 is a likely target for amplification, and that over-expression of this gene may contribute to development and/or progression of lymphomas and other tumors.     

Osteoclast-type giant cell tumor of the endometrium. An immunohistochemical study

We present a rare case of a 55 year old female with an osteoclast-type giant cell tumor of the endometrium associated with leiomyoma and adenomyosis. Multinucleated giant cells and mononuclear stromal cells reacted with vimentin and alpha-1-antichymotrypsin (AACT) using the immunoperoxidase method. Epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and keratin exhibited negative immunoreaction in these tumor cells. Our immunohistochemical results do not support the epithelial origin of an osteoclast-type giant cell tumor and mesenchymal derivation appeared more likely, suggesting histiocytic origin.     

A CASE OF MYCOSIS FUNGOIDES

The clinical history and pathological findings of a 68-year-old female with mycosis fungoides were described.
Clinically she developed cutaneous eruptions, and plaques to nodules appearlng within the next 4 months. Histopathological examination at biopsy revealed mycosis fungoides. At autopsy, extensive visceral involvement was disclosed (lungs, liver, kidneys, spleen, esophagus, left adrenal gland, lumbar vertebral bone marrow, and lymph nodes). Acute exacerbation of pulmonary tuberculosis was thought to be a terminal event.