We investigated the properties of glycine-induced responses in Cajal-Retzius cells, a neuronal cell type essential for the establishment of neocortical lamination. Whole-cell and gramicidin-perforated patch-clamp recordings were performed on visually identified Cajal-Retzius cells in tangential slices from neonatal rat cortex (postnatal days 0-3). With a pipette Cl(-) concentration of 50 mM, bath application of 1 mM glycine induced a membrane depolarization of 32.8+/-7.4 mV and a massive decrease in membrane resistance by 88+/-1.4%. The membrane depolarization was abolished in the presence of the glycinergic antagonists strychnine (30 microM) and phenylbenzene-omega-phosphono-alpha-amino acid (100 microM), while the GABA(A) receptor antagonist bicuculline (100 microM) and the glutamatergic antagonist (+/-)-2-amino-5-phosphonopentatonic acid (60 microM) were without effect, suggesting that the glycine-induced membrane responses were mediated exclusively by the strychnine-sensitive glycine receptor. The EC(50) for activation of glycine receptors was 0.54 mM, 1.62 mM and 2.41 mM, for the glycinergic agonists glycine, beta-alanine and taurine, respectively. Since the reversal potential of the glycine-induced currents showed a strong dependency on the intracellular chloride concentration and was virtually unaffected under HCO(3)(-)-free conditions, the activation of glycine receptors was probably linked to Cl(-) fluxes with little contribution of HCO(3)(-) ions. Perforated patch recordings from Cajal-Retzius cells demonstrated that glycine elicited depolarizing responses mediated by Cl(-) currents which reversed at -41+/-3.7 mV. In summary, from these results we suggest that Cajal-Retzius cells of the neonatal rat cerebral cortex express functional strychnine-sensitive glycine receptors that mediate depolarizing membrane responses via Cl(-) efflux.

Animals↗

PubMed2002

Novel mechanism of action hypothesized for stellate ganglion block related to melatonin.

The mechanism of action of stellate ganglion block has generally been explained by vasodilation within its sphere of innervation. However, the success of treatment cannot always be explained by just one mechanism of action, because its clinical indications in Japan extend to many diseases, including systemic diseases. We propose a new mechanism of action for stellate ganglion block that is based on correction of melatonin rhythm disorder resulting from increased sympathetic nerve tone and does not involve vasodilation.

Animals↗

PubMed2002

Interferon retreatment reduces or delays the incidence of hepatocellular carcinoma in patients with chronic hepatitis C.

Inhibition of hepatocarcinogenesis is a crucial issue in treating chronic hepatitis C patients, especially those who do not respond completely to interferon therapy. Interferon has been reported to reduce the incidence of hepatocellular carcinoma (HCC) not only in sustained virological responders but also in transient biochemical responders. However, the incidence of HCC increases in 5 years or more after interferon therapy in transient biochemical responders. The aim of this study is to assess whether interferon retreatment reduces the incidence of HCC in chronic hepatitis C patients in whom hepatitis C virus was not eradicated during initial interferon therapy. We enrolled 309 patients who were not sustained virological responders after initial interferon treatment consisting of a total dose of more than 250 megaunits of interferon and were followed for more than 2 years after treatment. Ninety-nine patients received interferon retreatment and 210 did not. Two courses of interferon therapy were administered in 84, three courses in 14 and five courses in one. The incidence of HCC was compared between patients with retreatment and those without. In the clinical characteristics, retreated patients were younger and followed up for a longer time period. The cumulative incidence of HCC was significantly lower in retreated patients. In multivariate analysis, patients' age (P=0.018) and the number of courses of interferon therapy (P=0.022) were independently associated with HCC incidence. These results suggest that interferon retreatment reduces or delays the incidence of HCC in chronic hepatitis C patients who did not completely respond to initial therapy.

Adult↗

PubMed2002

The possible involvement of micro-organisms other than Helicobacter pylori in the development of rectal MALT lymphoma in H. pylori-negative patients.

It remains unclear whether lymphoma of the mucosa-associated lymphoid tissue (MALT) in the extragastric organs is related to Helicobacter pylori infection or not. This report describes three patients with rectal MALT lymphoma negative for H. pylori infection, all of whom showed disease regression after being treated with antibiotics. One patient had MALT lymphoma in both the descending colon and the rectum; the other two patients had rectal disease only. None of the patients had chronic gastritis which was detectable either endoscopically or histologically and H. pylori infection was completely ruled out by various methods, including a urease breath test. These patients received antibiotic therapy. In all the patients, regression of MALT lymphoma was observed endoscopically and histologically, and polymerase chain reaction revealed that a previously observed rearranged band of immunoglobulin heavy chain had also disappeared after antibiotic treatment. These cases therefore suggest involvement of micro-organisms other than H. pylori in the development of rectal MALT lymphoma.

Adult↗

PubMed2002

Induction of cytochrome P4501A1 by autoclavable culture medium change in HepG2 cells.

1. Without the addition of xenobiotics, only by changing the culture medium can one induce extensively and transiently cytochrome P4501A1 (CYP1A1) protein and mRNA in human hepatoma HepG2 cells. The induction was aryl hydrocarbon receptor (AhR)-dependent, and was proven by: (1) the medium change activated the AhR, as judged by a electrophoretic mobility shift assay; and (2) the AhR inhibitor alpha-naphthoflavone inhibited the medium change-mediated induction. 2. Induction of CYP1A1 was related to medium prepared by autoclaving. By screening the ingredients in the medium, the serum had no effect on CYP1A1 induction, whereas both photo-oxidized and autoclaved tryptophan were shown to induce CYP1A1, as indicated by CYP1A1 protein or ethoxyresorufin-O-deethylase activity. The autoclaved tryptophan contained in an autoclavable medium was a more potent inducer of CYP1A1 than photo-oxidized tryptophan. 3. The results provide some practical suggestions with experiments related to CYP1A1.

Cell Line↗

PubMed2002

Images in cardiology: Narrowing of the thoraco-abdominal aorta.

Explore the source record for details and available documents.

Aorta, Abdominal↗

PubMed2002

Glomus tumor in the digit of a cat.

A solitary mass approximately 1.5 x 2 cm located on the outer side of the third digit of the left forepaw of a 7-year-old male cross-breed cat was examined pathologically. The excised tumor mass was hard and white and located within the deep dermis and subcutis. Histopathologically, the mass consisted of a mixed population of small round epithelioid cells arranged in ribbon- or cordlike structures and spindle-shaped cells forming loose irregular bundles in a mucinous stroma. The epithelioid cells were often arranged around small blood vessels. Neoplastic cells were intensely positive for vimentin and alpha smooth muscle actin and negative for keratin, desmin, S-100 protein, and neuron-specific enolase. Based on these pathologic features, the tumor was diagnosed as a glomus tumor, a neoplasm not previously reported in cats and extremely rare in animals.

Animals↗

PubMed2002

Immunomodulatory effects of prolactin and growth hormone in the tilapia, Oreochromis mossambicus.

To clarify the roles of prolactin (PRL) and GH in the control of the immune system, the effects of environmental salinity, hypophysectomy, and PRL and GH administration on several immune functions were examined in tilapia (Oreochromis mossambicus). Transfer from fresh water (FW) to seawater (SW) did not alter plasma levels of immunoglobulin M (IgM) and lysozyme. The superoxide anion (O(2)(-)) production in head kidney leucocytes accompanied by phagocytosis was elevated in SW-acclimated fish over the levels observed in FW fish. Hypophysectomy of the fish in FW resulted in a reduction in O(2)(-) production in leucocytes isolated from the head kidney, whereas there was no significant change in plasma levels of IgM or lysozyme. Treatment with tilapia GH and PRLs (PRL(177) and PRL(188)) enhanced O(2)(-) production in vitro in head kidney leucocytes in a dose-related manner. Extrapituitary expression of two PRLs, GH and IGF-I mRNA was detected in lymphoid tissues and cells such as head kidney, spleen, intestine and leucocytes from peripheral blood and head kidney. PRL-receptor mRNA was detected in head kidney leucocytes, and the level of expression was higher in SW-acclimated fish than that in FW fish. Treatment with PRL(177) caused higher production of O(2)(-) in the head kidney leucocytes isolated from SW tilapia than that from FW fish. In view of the fact that PRL acts antagonistically to osmoregulation in SW, its immunomodulatory actions in this euryhaline fish would appear to be independent of its osmoregulatory action.

Adaptation, Physiological↗

PubMed2001

Inhibitor complexes of the Pseudomonas serine-carboxyl proteinase.

Crystal structures of the serine-carboxyl proteinase from Pseudomonas sp. 101 (PSCP), complexed with a number of inhibitors, have been solved and refined at high- to atomic-level resolution. All of these inhibitors (tyrostatin, pseudo-tyrostatin, AcIPF, AcIAF, and chymostatin, as well as previously studied iodotyrostatin and pseudo-iodotyrostatin) make covalent bonds to the active site Ser287 through their aldehyde moieties, while their side chains occupy subsites S1-S4 of the enzyme. The mode of binding of the inhibitors is almost identical for their P1 and P2 side chains, while significant differences are observed for P3 and P4 (if present). Kinetic parameters for the binding of these nanomolar inhibitors to PSCP have been established and correlated with the observed mode of binding. The preferences of this enzyme for a larger side chain in P2 as well as Tyr or Phe in P1 are explained by the size, shape, and characteristics of the S2 and S1 regions of the protein structure, respectively. Networks of hydrogen bonds involving glutamic and aspartic acids have been analyzed for the atomic-resolution structure of the native enzyme. PSCP contains a calcium-binding site that consists of Asp328, Asp348, three amide carbonyl groups, and a water molecule, in almost perfect octahedral coordination. The presence of Ca(2+) cation is necessary for the activity of the enzyme.

Binding Sites↗

PubMed2001

Involvement of MAP kinase cascades in Smad7 transcriptional regulation.

Smad7 transcription is known to be regulated by TGF-beta to form a negative-feedback loop of TGF-beta-mediated biological responses. In this study, we sought to determine whether other signaling cascades, especially mitogen-activated protein (MAP) kinases, might be involved in the transcriptional regulation of Smad7. Hyperosmolarity (500 mOsm/kg H(2)O) or anisomycin (10 microg/ml) potentiated TGF-beta-induced increases of Smad7 mRNA abundance in normal rat kidney fibroblasts. SB203580 (10 microM) treatment had no effect on basal and TGF-beta-induced Smad7 mRNA abundance, and the overexpression of kinase-negative ATF2 had no effect on Smad7 promoter activity. On the other hand, overexpression of dominant-negative JNK and dominant-negative c-Jun significantly attenuated the TGF-beta-induced increases of Smad7 mRNA abundance and promoter activity, respectively. Mutations of the AP-1 element near the Smad-binding element in the rat Smad7 promoter also completely abolished TGF-beta-induced Smad7 promoter activity. These results suggested that the JNK cascade, not p38 kinase, cooperated with the Smad signaling to induce Smad7 transcription through the AP-1 element. Serum treatment (10%) attenuated the TGF-beta-induced Smad7 mRNA increase, and PD98059 (30 microM) treatment increased the basal and TGF-beta-induced Smad7 promoter activity. Gel shift analysis revealed that serum treatment decreased the amount of nuclear Smad complex that PD98059 treatment was shown to restore. These results indicated that ERK activation negatively regulated Smad7 transcription possibly by inhibiting translocation of Smad complex to nuclei. In conclusion, JNK cascade and ERK cascade are important positive and negative regulators of Smad7 transcription, respectively.

Animals↗

PubMed2001

Rectal immunization with antigen-containing microspheres induces stronger Th2 responses than oral immunization: a new method for vaccination.

The rectum as an effective site for induction of systemic and local immunity has received little attention. Rectal immunization with microspheres-containing ovalbumin (MS-OVA) was tested for its ability to elicit systemic and mucosal immune responses. Rectal immunization with MS-OVA enhanced both Th2 dominant OVA-specific IgG levels in the serum and OVA-specific IgA levels in fecal extracts more prominently than did oral immunization. Cytokine analysis of CD4(+) T cells indicated a predominant induction of Th2-type responses compared to Th1-type responses following rectal immunization compared to oral immunization. These results demonstrate that rectal immunization with microspheres could be an effective new vaccination method.

Administration, Oral↗