Sensitizing effects of bradykinin on the heat responses of the visceral nociceptor.

1. Whether bradykinin (BK), which is known as an endogenous pain-producing substance, induces augmentation of the discharges of polymodal receptors evoked by heat stimulation was investigated in in vitro canine testis-superior spermatic nerve preparations. 2. The heat response was significantly augmented by pretreatments with BK at concentrations greater than 0.094 nM, whereas BK induced significant increases in the mean discharge rates at concentrations above 9.4 nM. Both effects increased in a concentration-dependent manner. The augmenting effect of BK on the heat response diminished within 10 min after application of BK, regardless of concentration. 3. When 9.4 nM BK was applied in a mixture with 940 nM NPC349, a B2 receptor antagonist, the averaged mean discharge rate evoked by BK and the averaged augmenting effect were both significantly suppressed compared with those induced by BK given alone. 4. The augmenting effect of BK on the heat response of polymodal receptors could be observed even in the absence of BK-evoked discharges per se in several cases in which low concentrations of BK or BK plus B2 antagonists were given. 5. These findings suggest that the augmenting effects of BK on the heat response depend on B2 receptor-mediated intracellular processes acting in parallel to, but not directly on, the impulse-generation mechanism of the heat response of the polymodal receptor.     

A case report of aorto-pulmonary window associated with atrial septal defect]

The patient was a one-year-old boy, who underwent surgery with a diagnosis of atrial septal defect (ASD). During operation, aorto-pulmonary window (A-P window) which had not been detected by the preoperative examinations, was found. Therefore, the A-P window was divided prior to closing ASD. The patient is in good condition six months after the operation. The causes of the inaccurate preoperative diagnosis were discussed.     

Ammonia: a possible promotor in Helicobacter pylori-related gastric carcinogenesis.

Helicobacter pylori (HP) has been shown to possibly be a pathogen of gastric carcinoma. HP has urease activity and produces ammonia in the stomach. In this study, the role of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in rats. After 24 weeks pretreatment with MNNG (83 mg/l), 0.01% ammonia or tap water as a drinking water was administered for 24 weeks. The ammonia-treated rats showed a significantly higher incidence of gastric cancer (percent of animals with tumors and number of tumors per rat). Ammonia would thus appear to have an important role in HP-related human gastric carcinogenesis.     

Transcriptome analysis of hagfish leukocytes: a framework for understanding the immune system of jawless fishes

Jawless fishes occupy a critical phylogenetic position in understanding the origin of the adaptive immune system. Here, we performed large-scale expressed sequence tag analysis of leukocytes isolated from the inshore hagfish Eptatretus burgeri. Although we found many immunity-related genes such as those involved in lymphocyte or hematopoietic cell signaling and development as well as cytokine and cytokine receptor genes, MHC molecules or antigen receptors were not identified. We characterized two hagfish cDNAs that closely resembled mammalian proteins with essential roles in adaptive immunity, one encoding a GATA3-like molecule and another encoding a Bruton's tyrosine kinase (Btk)-like molecule. The GATA3-like gene of hagfish was equidistant from GATA3 and GATA2 in jawed vertebrates. Similarly, the hagfish Btk-like molecule was not Btk itself, but qualified as a pre-duplicated form of Btk and Bmx in jawed vertebrates. In total, our work provides circumstantial evidence that adaptive immunity is unique to jawed vertebrates.     

Effects of adrenoceptor antagonists on the cutaneous blood flow increase response to sympathetic nerve stimulation in rats with persistent inflammation

There is some evidence that the sympathetic nervous system plays a role in the development and/or maintenance of painful states, and that sympathetic nervous function is altered in these conditions. Our previous experiments showed that electrical stimulation of the lumbar sympathetic trunk (sympathetic stimulation: SS), which normally induces a decrease in blood flow (BF) of plantar skin, induced its BF increase in about 50% of adjuvant-inflamed rats. To investigate the mechanism of this BF-increase response, we examined whether noradrenaline (NA) plays any role in this changed response to SS, and which receptor subtype is involved. We measured paw cutaneous BF response with a laser Doppler flowmeter in rats chronically inflamed with complete Freund's adjuvant. SS induced the BF-increase response in 50-67% of measured sites. Close-arterially injected NA induced the BF-increase response at dosages between 10-100 ng/kg only at the sites with the BF-increase response to SS. The BF-increase and -decrease responses to NA was significantly reduced after the close-arterial injection of either alpha1- or alpha2-adrenoceptor antagonists (p lt; 0.05, respectively). In contrast, although the BF-decrease responses to SS were significantly reduced by administration of alpha1- and alpha2-adrenoceptor antagonist, BF-increase response was reduced only by alpha1-adrenoceptor antagonist, and that only at a higher dose. In addition, the beta-adrenoceptor antagonist had no effects on both responses. These results suggest that the BF-increase response to SS involves, additionally to NA, a non-adrenergic mechanism.     

In vivo depletion of macrophages by desulfated iota-carrageenan in mice

Almost 90% of the sulfate groups of iota-carrageenan (CGN) was removed with acid-methanol in an attempt to obtain a product which would selectively eliminate macrophages in mice. Desulfated CGN(DS-CGN) failed to induce in vivo polyclonal antibody production in DBA/2 mice. However, the number of phagocytes in the peritoneal cavity, spleen, thymus and lymph node of DBA/2 mice was reduced stringently by DS-CGN treatment. The number of Mac-1 positive cells(macrophages) in DS-CGN-treated mice gradually decreased for at least 7 days after the last injection of DS-CGN. In contrast, the relative proportion of T and B lymphocytes in the lymphoid organs was unaffected by DS-CGN treatment. DS-CGN suppressed antibody responses to SRBC, a T cell and macrophage-dependent antigen, but no such suppressive effect was observed in the polyclonal antibody responses to LPS, a T cell and macrophage-independent B cell activator. Furthermore, the impaired SRBC antibody responses in DS-CGN-treated mice were restored following transfer of adherent cells but not T cells. These experimental results indicate that DS-CGN selectively eliminates macrophages without influencing lymphocyte function in vivo.     

The role of renal macrophages in the aglomerular kidney of the sea-horse (teleost) in the removal of exogenous macromolecules from circulating blood

Mechanisms involved in the removal of exogenous macromolecules from circulating blood were investigated in the aglomerular nephrons of the kidney of the sea-horse, Hippocumpus kuda Bleeker, using either native anionic or cationized probes. After intraperitoneal injection of native anionic horse-spleen ferritin (HS-AF) or cationized one (HS-CF) into the sea-horse, kidneys and gills were examined morphologically at intervals of 1 h to 14 days. Histochemical and immunohistochemical studies and transmission electron microscopy of the kidneys revealed that most of the injected HS-AF or HS-CF were taken up by macrophages in the sinusoids of hemopoietic tissue through pinocytosis, being gradually accumulated into their phagolysosomes. By the 14th day, the injected ferritin particles were degraded and the ferric agglomerates were concentrated within the phagolysosomes. Then the macrophages heavily laden with densely packed ferric catabolites migrated into the hemopoietic area forming macrophage agglomerates or macrophage centers. Some HS-AF and HS-CF particles infiltrated into the tubular basement membrane, where they were taken up by the tubular epithelial cells through pinocytosis, translocated into the phagolysosomes, fragmented into small ferric catabolites and then excreted into the urinary space. In contrast, examination of the gills revealed neither HS-AF, HS-CF particles nor their histochemically detectable ferric catabolites in either the interstitial space including basal lamina or the alveolar epithelia. It seems that no appreciable egress of exogenous substances occurs from the gill into the environmental water.     

Immunopharmacological study of CCA (Lobenzarit disodium), an anti-arthritis agent--I. Abrogation of IL 1 secretion by LPS-stimulated human monocytes and induction of gamma-interferon production with CCA

In vitro effects of CCA, an anti-arthritis agent, were studied upon autologous mixed lymphocyte reaction (AMLR), lymphocyte mitogenesis, IL 1 and IL 2 production, immunoglobulin production and gamma-interferon (IFN) production. CCA at 50 micrograms/ml, which was not toxic to cells, blocked AMLR, IL 1 production and immunoglobulin production (IgM and IgG) significantly, while CCA at the same dose did not affect IL 2 production and lymphocyte mitogenic responses to Staphylococcus aureus Cowan I(SAC) and pokeweed mitogen(PWM). CCA at both 20 ng/ml and 20 micrograms/ml induced human gamma/IFN. Addition of IL 1 and/or IL 2 reversed inhibitory effect of CCA on AMLR. These data suggest that CCA exerts its actions by mainly affecting T cells and monocytes and can be used as an immunomodulator.