Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production

Helicobacter pylori can produce a persistent infection in the human stomach, where chronic and active inflammation, including the infiltration of phagocytes such as neutrophils and monocytes, is induced. H. pylori may have a defense system against the antimicrobial actions of phagocytes. We studied the defense mechanism of H. pylori against host-derived peroxynitrite (ONOO(-)), a bactericidal metabolite of nitric oxide, focusing on the role of H. pylori urease, which produces CO(2) and NH(3) from urea and is known to be an essential factor for colonization. The viability of H. pylori decreased in a time-dependent manner with continuous exposure to 1 microM ONOO(-), i.e., 0.2% of the initial bacteria remained after a 5-min treatment without urea. The bactericidal action of ONOO(-) against H. pylori was significantly attenuated by the addition of 10 mM urea, the substrate for urease, whereas ONOO(-)-induced killing of a urease-deficient mutant of H. pylori or Campylobacter jejuni, another microaerophilic bacterium lacking urease, was not affected by the addition of urea. Such a protective effect of urea was potentiated by supplementation with exogenous urease, and it was almost completely nullified by 10 microM flurofamide, a specific inhibitor of urease. The bactericidal action of ONOO(-) was also suppressed by the addition of 20 mM NaHCO(3) but not by the addition of 20 mM NH(3). In addition, the nitration of L-tyrosine of H. pylori after treatment with ONOO(-) was significantly reduced by the addition of urea or NaHCO(3), as assessed by high-performance liquid chromatography with electrochemical detection. These results suggest that H. pylori-associated urease functions to produce a potent ONOO(-) scavenger, CO(2)/HCO(3)(-), that defends the bacteria from ONOO(-) cytotoxicity. The protective effect of urease may thus facilitate sustained bacterial colonization in the infected gastric mucosa.     

Variation of the conserved neutralizing epitope in influenza B virus victoria group isolates in Japan

For almost 20 years, the neutralizing-epitope site specific for influenza B virus Victoria group isolates was conserved at the "tip" of the hemagglutinin molecule; however, it was not detected in half of the isolates from the 2002-2003 epidemic in Japan. Amino acid substitutions (D164E or N165K) were observed at the "tip", and the epitope was altered. The viral antigenicities were affected, and human antibodies did not substantially inhibit the hemagglutination in the hemagglutination inhibition tests. It is suspected that such variants will be important in future epidemics.     

Human cytomegalovirus infection in foci of Langerhans cell histiocytosis

 Langerhans cell histiocytosis (LCH) has been thought to be a disorder of immune regulation, and increasingly, evidence showing that the tissue damage in LCH involves lymphokines and pro-inflammatory cytokines is reported. We detected human cytomegalovirus (HCMV)-DNA in LCH cells in the foci of LCH lesions by immunohistochemistry, in situ hybridization and PCR. HCMV was detected in the nuclei and/or cytoplasm of LCH cells in 9 of 27 LCH cases by immunostaining. HCMV was probably an early antigen. In situ hybridization revealed signals for HCMV-DNA only in the nuclei of LCH cells in 10 of the 27 LCH cases. PCR analysis was performed in 20 of the LCH cases, and HCMV-DNA was detected in 7 of these. All 7 positive cases were also positive for HCMV by ISH and IHC. These findings suggested that early phase infection or reactivation of HCMV occurred in the LCH lesions. HCMV infection may be accompanied by impaired cytokine production. Our study also suggested a relationship between HCMV infection and expression of TNFα. In tissues affected by LCH, dermatopathic lymphadenopathy or malignant fibrous histiocytoma and in normal tissues no signals for Epstein-Barr virus-RNA were detected. These findings suggest that in some cases LCH is associated with HCMV infection. Received: 24 November 1998 / Accepted: 24 April 1998     

Mixed growth hormone cell- prolactin cell pituitary adenoma with acromegaly: α-subunit most growth hormone cells

A 51 -year-old woman with mixed growth hormone (GH) cell-prolactin (PRL) cell pituitary adenoma is presented. She had clinical signs due to hypersecretion of GH and PRL. Resected tissue was studied immunohistochemically and morphologically. The serial sections revealed that GH and α-subunit were co-localized in most cells, while GH and PRL were localized in different cells.     

Metanephric adenoma of the kidney

A case of a rare renal tumor showing characteristic histo-logic features is presented. The patient was a 54 year old female, whose renal tumor was incidentally detected on abdominal ultrasound (US) examination. Ultrasound, computed tomography and angiography findings were consistent with a diagnosis of renal cell carcinoma of the hypovascular type. Left nephrectomy was performed. The tumor, which measured 2.6 times2.6 times 2.5 cm, was located in the left renal cortex, and had a uniformly whitish-yellow cut surface and well-defined margin. Histologically, the tumor was characterlzed by its monomorphous growth pattern and was composed of uniformly small cells arranged in a tubular or rosette-like pattern. The tumor cells had scant cytoplasm and the nuclei were small, round and regular. These histo-logic features resembled the epithelial elements of a metanephric hamartoma in the nephroblastomatosis complex in infants. However, there was no mitosis and cellular atypia was minimal, suggesting benignity. According to these his-tologic features, the diagnosis of metanephric adenoma was made. Its clinicopathologic features are discussed.     

TGF-β1 Null Mutation Leads to CD154 Upregulated Expression in Affected Tissues

The TGF-1(–/–) mouse is a murine model for systemic autoimmune disease. The aim of this study is to elucidate the immunological mechanism that leads to multifocal tissue inflammation and autoantibody production in TGF-1(–/–) mice. Heart, lung, liver, and salivary gland from TGF-1(–/–) were assessed for CD154 expression by RT-PCR and immunohistochemistry. Compared to wild-type littermates, CD154 expression was elevated in all tissues studied. Furthermore, IL-12 mRNA was expressed in the salivary gland and heart of TGF-1(–/–) mice and not in wild-type littermates. This suggests that the CD154 pathway is activated in these tissues. This shows that TGF-1 regulates CD154 expression leading to spontaneous IL-12 production and autoimmunity.     

Effects of dopamine antagonists on neuronal activity related to a delayed response task in monkey prefrontal cortex

1. Using iontophoretic techniques, we investigated the influence of dopamine (DA) antagonists [haloperidol (HAL), a non-selective DA antagonist; sulpiride (SUL), a selective antagonist for D2 receptors; and fluphenazine (FLU), a potent antagonist for D1 receptors] on neuronal activity related to a delayed response (DR) task in the monkey prefrontal cortex (PFC). The DR task was initiated by the rotation of a handle to a central zone and consisted of seven distinct periods: an initial intertrial interval of 0.3 s, a precue period of 1 s (a center green lamp), a cue period of 1 s (left or right lamp), a delay period of 4 s, a go period (red lamp in the center; rotation of the handle to either the left or right zone), a hold period (holding of the handle in either the left or right zone), and a final reward period. Because it was shown, as described in the companion paper (Sawaguchi et al. 1990), that DA augments the increased activity of prefrontal neurons related to the cue, delay, and go periods of the DR task, effects of the DA antagonists were examined in a total of 61 neurons that showed increases in activity related to these periods and a response to DA. 2. Consistent with previous studies (Sawaguchi et al. 1988a, 1990), iontophoretically applied DA increased DR task-related activity in prefrontal neurons. Iontophoretically applied HAL and FLU antagonized the increased effect of DA on the task-related activity. By contrast, SUL did not have any clear effects on the influence of DA. 3. By themselves, HAL and FLU reduced prefrontal neuronal activity related to the cue, delay, and go periods of the DR task. The ratio of the reduction by HAL and FLU was significantly larger for activity during the cue, delay, or go period than for background activity during the precue period; and, as a result, the signal-to-noise (S/N) ratio of the task-related activity to background activity was reduced during the application of HAL and FLU. In contrast, SUL did not have any clear effects on activity related to the cue, delay, and go periods of the DR task, and the S/N ratio during the application of SUL did not significantly differ from that before the application of the drug.(ABSTRACT TRUNCATED AT 400 WORDS)     

Histological properties and biological significance of pouch in red kangaroo, Macropus rufus

2 embryos, 4 youngs, 4 older youngs and the pouch of 2 mothers of the red kangaroos were examined. The results obtained are as follows: 1. The initial muscle spindles are already observed light microscopically in the vertebral, dorsal neck and forelimb muscles of the newborn baby and a little bit later in the masticatory muscles of the young of 68 mm in craniorump length and 28 g in body weight. 2. In the skin with less hair lining the inner surface of the pouch, abundant apocrine large sweat glands are observed, especially surrounding the basal region of the nipple and in the pleat formation of the skin. 3. The lactiferous mammary gland is enlarged, the lobules being divided by the interlobular muscle fiber tissue and enwrapped by the muscular capsule. The milk is squirted automatically by the muscle fiber contraction from the gland to the nipple, to which the baby attaches itself. 4. The musculature of the pouch wall is developed to form the sphincter muscle in the pouch orifice. The sphincter muscle plays an important role in conditioning the optimum temperature for the naked baby inside the pouch. 5. The apocrine perfume plays an important role in guiding the baby on the journey to the pouch after birth and the apocrine products also in maintaining the optimum humidity of the pouch to accomodate the baby. 6. During the long period of stay in the pouch, the masticatory and locomotive systems and their neuromuscular mechanism related to the herbivorous mastication become fully established and then the young leaves the pouch to feed on the animal's proper diet.