Strong Telomerase Activity of B Lymphocyte from Mesenteric Lymph Nodes of Patients with Inflammatory Bowel Disease

Telomerase acitivity can be induced in human B lymphocytes by in vitro stimulation of their antigen receptors. To determine whether telomerase activity is induced in vivo, we analyzed telomerase activity in B lymphocytes from the mesenteric lymph nodes of patients with inflammatory bowel disease (IBD), whose lymph nodes are well known to be strongly stimulated, and from those of noninflamed controls. Seven IBD patients and 4 noninflamed controls were enrolled. Telomerase activity was assayed by telomeric repeat amplification protocol with minor modifications. The mesenteric lymph nodes from patients with IBD had stronger telomerase activity than those from controls or peripheral mononuclear cells. Isolation of CD19⁺ B lymphocytes from these lymph nodes showed that this strong activity resides in this lymphocytes subpopulation. This study provides the evidence that telomerase activity is induced in human B lymphocytes in human inflammatory disease.     

Structural model of human ceruloplasmin based on internal triplication, hydrophilic/hydrophobic character, and secondary structure of domains.

A molecular model for the structure of human ceruloplasmin is proposed that is based on the determination of the complete amino acid sequence, studies of the products of limited proteolytic cleavage, calculations of the hydrophilic/hydrophobic character (hydropathy profile), and predictions of the local secondary structure. This multicopper oxidase (Mr approximately 132,000) consists of a single polypeptide chain (1046 amino acid residues) with four attached glucosamine oligosaccharides. Computer-assisted statistical analysis of the internal repetition in the amino acid sequence confirms that the entire polypeptide chain is divided into three contiguous homology units, each containing about 350 amino acid residues. Each homology unit is subdivided into three domains, designated A1, A2, and B, that differ in structure and probably in function. Calculations of the hydropathy profile and predictions of the secondary structure support a molecular model based on internal repetition of three homology units and help to identify characteristic features of the interdomain junctions. The alignment scores for internal duplication of pairings of the three homology units of ceruloplasmin exceed the scores yet reported for contiguous internal duplication of any other protein. This highly significant evidence for intragenic repetition suggests that the ceruloplasmin molecule evolved by tandem triplication of ancestral genes coding for a primordial copper oxidase.     

A case of pulmonary tuberculosis associated with severe respiratory failure, DIC and intractable bilateral pneumothoraces]

We had a sixty-five year old male patient who suddenly complained of dyspnea and fever with pulmonary tuberculosis, severe respiratory failure, disseminated intravascular coagulation (DIC) and intractable bilateral pneumothoraces. From the first hospital day severe hypoxemia which did not respond to conventional oxygen therapy developed with a diffuse ill-defined reticulo-nodular shadow in the plain chest x-ray film. On the 2nd hospital day mechanical ventilation with 2cmH2O PEEP was introduced. Antituberculous agents as well as corticosteroids were started suspecting acute interstitial pneumonia with pulmonary tuberculosis and adult respiratory distress syndrome (ARDS). Medication was followed by the treatment of Gabexate mesilate and heparin against DIC on laboratory data. Though clinical findings and pulmonary infiltrate on chest x-ray film transiently improved, right pneumothorax occurred suddenly on the 6th day followed with left pneumothorax on the 36th day. Tube drainage of both pleural spaces and repeated instillation of thrombin-rich oxycel cotton via bronchofiberscope failed to stop air leakage. He ultimately expired on 49th hospital day. At postmortem lung had multiple bilateral bulla several of which ruptured to the pleural site and caseating necrotic area containing bacilli positively stained with Ziehl-Nielsen stain in the bilateral upper lobe. No typical caseating necrotic lesion, however, was found in the other lung tissue. Therefore, it seemed to show a chronic phase of diffuse alveolar damage (DAD).     

Regulation of circulating immune complexes by complement receptor type 1 on erythrocytes in chronic viral liver diseases

BACKGROUND AND AIM: Complement receptor type 1 (CR1) is a transmembrane protein, and human erythrocyte CR1 (E-CR1) is involved in the transport of circulating immune complexes (IC) from the circulation to the reticuloendothelial system, including the liver and spleen. In chronic viral hepatitis, increased levels of IC containing viral particles and an association with various extrahepatic manifestations have been reported. However, regulatory mechanisms for IC levels are not fully understood. PATIENTS/SUBJECTS AND METHODS: We analysed IC, E-CR1, and quantitative polymorphism of the CR1 gene in 149 patients with chronic viral liver diseases and in 64 normal blood donors using an enzyme linked immunosorbent assay, radioimmunoassay, and polymerase chain reaction-restriction fragment length polymorphism, respectively. We also analysed the effect of CR1 gene polymorphism on IC binding to E-CR1 using molecular methods. RESULTS: E-CR1 levels in patients with chronic hepatitis and chronic viral liver diseases as a whole correlated inversely with increased levels of IC. Moreover, significantly high levels of IC were observed in patients with chronic hepatitis C (CH-C) who were homozygous for the E-CR1 low density allele. We also found low levels of E-CR1 in liver cirrhosis and CH-C but not in CH-B. Low levels of E-CR1 in CH-C were observed, even after considering the polymorphism of the CR1 gene. Finally, we demonstrated CR1 gene polymorphism dependent binding of hepatitis virus containing IC. CONCLUSIONS: Our results emphasise the important role of E-CR1 in clearance of IC from the circulation and the acquired, rather than inherited, decrease in E-CR1 in chronic viral liver diseases, especially of type C.     

A SHV-derived extended-spectrum beta-lactamase (SHV-12) produced by an Escherichia coli recovered from wound abscess in post operative case with rectal carcinoma

A 62-year-old woman admitted for rectal carcinoma suffered from a post-operative bacterial infection. Oxy-imino-beta-lactams including cefotiam (CTM) and cefozopran (CZOP) were prescribed for this case, but the patient developed a wound abscess followed by peritonitis. She recovered from the bacterial infection after drainage and recurrent washing of the abscess. An ephemeral aggravation of infectious signs was observed just after creation of an artificial anus, and CZOP was again administered, and no evident bacterial infection occurred. The patient recovered, then was followed as an outpatient to date. A CAZ-resistant (MIC, > 16 micrograms/ml) E. coli was recovered from pus of her wound abscess. Since the CAZ-resistance decreased (MIC, 64 micrograms/ml-->0.13 microgram/ml) by the presence of clavulanate (CVA) in this isolate, this strain was speculated to be an extended spectrum beta-lactamase (ESBL) producer at an early stage of infection. A similar strain was also isolated from the feces. Therefore, we immediately took measures to block the nosocomial spread of this microorganism, and we succeeded in preventing a nosocomial outbreak of this strain. It was later confirmed by PCR analysis and DNA sequencing analysis that this CAZ-resistant E. coli strain produces an ESBL (SHV-5-2a = SHV-12). This is the first report of a case of infection with SHV-derived ESBL producing E. coli strain in Japan. We are concerned that further dissemination of this kind of microorganism might occur in the near future also in Japan, as it has been widely observed in European countries and the US. We believe that it will be very important to distinguish the type of beta-lactamases for rigorous bacterial infection control with the prudent use of antibiotics. In other words, we in Japan must recall that various gram-negative bacterial species that produce TEM-, SHV-derived ESBLs, Toho-1, AmpC, or IMP-1 are already widespread. Thus, we should take this fact into consideration when we do antibiotic susceptibility tentings and interpretation of the results for promotion of accurate chemotherapy.     

Age-related change in the amount of ubiquitinated histones in the mouse brain

We investigated age-related changes in the ubiquitination of histones in mouse brains. By Western blot analysis using rabbit anti-ubiquitin antibodies, histone H2A and H2B were found to be the only proteins that are ubiquitinated in the acid-extractable nuclear proteins of both young (4-month-old) and senescent (29-month-old) mouse brains. The proportion of ubiquitinated histones was about 30% higher in senescent mice than in young ones. When total brain homogenates were analyzed similarly using somewhat different age groups of the animals, the proportion in the old animals was about 2-fold higher than that in the young.     

Imaging of pulmonary emphysema: A pictorial review

The term ‘emphysema’ is generally used in a morphological sense, and therefore imaging modalities have an important role in diagnosing this disease. In particular, high resolution computed tomography (HRCT) is a reliable tool for demonstrating the pathology of emphysema, even in subtle changes within secondary pulmonary lobules. Generally, pulmonary emphysema is classified into three types related to the lobular anatomy: centrilobular emphysema, panlobular emphysema, and paraseptal emphysema. In this pictorial review, we discuss the radiological – pathological correlation in each type of pulmonary emphysema. HRCT of early centrilobular emphysema shows an evenly distributed centrilobular tiny areas of low attenuation with ill-defined borders. With enlargement of the dilated airspace, the surrounding lung parenchyma is compressed, which enables observation of a clear border between the emphysematous area and the normal lung. Because the disease progresses from the centrilobular portion, normal lung parenchyma in the perilobular portion tends to be preserved, even in a case of far-advanced pulmonary emphysema. In panlobular emphysema, HRCT shows either panlobular low attenuation or ill-defined diffuse low attenuation of the lung. Paraseptal emphysema is characterized by subpleural well-defined cystic spaces. Recent topics related to imaging of pulmonary emphysema will also be discussed, including morphometry of the airway in cases of chronic obstructive pulmonary disease, combined pulmonary fibrosis and pulmonary emphysema, and bronchogenic carcinoma associated with bullous lung disease.     

Vasoactive intestinal polypeptide and alpha 2-adrenoceptor agonists regulate adenosine 3',5'-monophosphate accumulation and melatonin release in chick pineal cell cultures

Vasoactive intestinal polypeptide (VIP) has been shown to stimulate melatonin synthesis in mammalian pineal; however, a regulatory role for VIP in the avian pineal has not been explored. Immunocytochemical and physiological response experiments were performed to investigate whether 1) immunoreactive VIP fibers innervated the avian pineal gland; 2) VIP had a specific effect on melatonin release that was mediated by cAMP stimulation; and 3) alpha 2-adrenergic signal transduction was associated with a reduction in cAMP levels. Immunocytochemical experiments demonstrated the presence of both tyrosine hydroxylase- and VIP-immunoreactive fibers in the avian pineal gland. Treatment of dispersed chick pineal cell cultures with VIP stimulated melatonin release (maximum 6-fold increase; EC50 = 1.8 nM) when administered during the 12-h light period of a 12-h light, 12-h dark cycle. Of the other four peptides tested [porcine VIP-(10-28), porcine peptide histidine isoleucine, porcine secretin, and human glucagon), only peptide histidine isoleucine stimulated melatonin release (EC50 = 30 nM). The effect of VIP was mediated by a time- and dose-dependent increase in cAMP accumulation (maximum 4-fold increase). The specific alpha 2-agonist UK-14,304 reduced cAMP accumulation (maximum 43% reduction) and inhibited melatonin release (EC50 = 19 nM) in the presence of 3 X 10(-8) M VIP. Norepinephrine-induced inhibition of nocturnal melatonin release was blocked by the elevation of cAMP achieved through the administration of forskolin (EC50 = 0.2 microM), isobutylmethylxanthine (EC50 = 112 microM), or 8-bromo-cAMP (EC50 = 166 microM). Collectively, these results demonstrate the presence and functional significance of VIP in the avian pineal gland, and the interaction of VIP and norepinephrine at the level of cAMP in the regulation of melatonin biosynthesis.