The protective effect of pyrroloquinoline quinone and its derivatives against carbon tetrachloride-induced liver injury of rats

Pyrroloquinoline quinone (PQQ) and its derivative, oxazo pyrroloquinoline (OPQ-G), protected rats from experimental liver injury induced by carbon tetrachloride (CCl₄) in vivo. This effect was observed after an intraperitoneal injection of 5 mg/kg PQQ or OPQ-G, which was given twice, 10 min and 1 h before CCl₄ administration. Pyrroloquinoline quinone protected primary cultured rat hepatocytes from CCl₄ toxicity in vitro. This protection was most effective at a concentration of 3 μmol/L PQQ. Pyrroloquinoline quinone derivatives (oxazo pyrroloquinoline, methyl-thioethyl oxazo pyrroloquinoline and PQQ-allylester) also protected the hepatocytes from CCl₄ toxicity. Pyrroloquinoline quinone and its derivatives inhibited the lucigenin-enhanced chemiluminescence from isolated hepatocytes initiated by CCl₄. These results suggest that eliminating free radicals is one of the protective mechanisms of PQQ and its derivatives against CCl₄-induced liver injury.     

A case of intractable diarrhea firmly suspected to have autoimmune enteropathy

Protracted diarrhea with insulin dependent diabetes mellitus (DM) and hypothyroidism in a 9 month old Japanese girl who was firmly suspected to have autoimmune enteropathy (AIE) is reported. Her severe secretory diarrhea failed to respond to intensive antidiarrheic treatment and was gradually improved with steroid therapy. The circulating autoantibodies to enterocytes in her serum were detected by indirect immunofluorescence technique and the impaired suppressor T (Ts) cell function was proved by plaque forming assay using bead-separated CD4 or CD8 T cells together with CD19 B cells. The anti-enterocyte antibodies were exclusively of immunoglobulin M (IgM) class and were detected with the progress of the protracted diarrhea. Maximum antibody titer was obtained at the onset of DM and the disappearance of autoantibodies was associated with the resolution of the clinical symptoms and signs. The helper functions of adult CD4 T cells to induce Ig-secreting cells from adult and the patient were strikingly suppressed by adult CD8 T cells. However, the CD8 T cells from the patient lost the ability to inhibit the induction of these Ig-secreting cells when stimulated with adult CD4 T cells. Moreover, the patient's CD8 T cells stimulated rather than suppressed the induction of Ig-secreting cells from the patient when stimulated with the patient's CD4 T cells. These results suggest that the impaired Ts cell function in this patient might play some immunological role in the pathogenesis of AIE     

CASE REPORT: A case of primary ileal carcinoma in a young woman and a review of the Japanese literature

We report a case of primary ileal carcinoma in a young woman, which was diagnosed definitively before operation. A 29-year-old woman presented with abdominal pain, diarrhoea and bloody stools. Colonoscopic and radiographic studies revealed that there was a 7.5 × 7 cm tumour (well-differentiated adenocarcinoma) at the terminal ileum, forming an ulcerated lesion at the centre. The tumour had invaded the caecum, the right urinary tract, the right ovary and a portion of the sigmoid colon. Fifty-three cases of primary ileal carcinoma were reported in Japan between 1982 and 1994 and their clinical features are reviewed herein.     

Mixed connective tissue disease in childhood: A nationwide retrospective study in Japan

Sixty-six children with mixed connective tissue disease (MCTD) were analyzed by a nationwide prospective study. The diagnostic significance of Raynaud's phenomenon and positive anti-RNP antibody was confirmed, and additional symtoms including swelling of fingers, facial erythema, and polyarthralgia, and laboratory findings such as positive rheumatoid factor, hypergammaglobulinemia, and increased levels of myogenic enzymes, were variably positive. These clinical and laboratory characteristics of MCTD were critically different from those of systemic lupus erythematosus, indicating that MCTD is an independent entity of disease.     

Hyperbaric oxygen stimulates cell proliferation and normalizes multidrug resistance protein-2 protein localization in primary rat hepatocytes

Hyperbaric oxygen therapy (HBO) has been used for many clinical treatments, including primary liver non-function. However, the cellular mechanism by which HBO treatment ameliorates liver function is not understood. Therefore, the purpose of this study was to elucidate this cellular mechanism using primary cultured rat hepatocytes in in vitro studies. Hepatocytes were treated with HBO at 1 day after plating, and the morphological and functional characteristics of bile canaliculi formed in cultured hepatocytes were observed by time-lapse microscopy. Multidrug resistance protein-2 localization was observed by confocal laser microscopy. In cultured hepatocytes, the labeling index in the HBO group at 2 days after treatment was significantly higher than that in the control group. In addition, the proliferating cellular nuclear antigen level in the HBO group was significantly higher than that in the control group. The contraction of the bile canaliculi in the HBO group was slower than in the control group and the dilatation of bile canaliculi in the HBO group was much larger than in the control group. Multidrug resistance protein-2 in the HBO group was localized at the apical membrane. These results show that HBO stimulates hepatocytes to proliferate and HBO normalizes multidrug resistance protein-2 localization to the apical membrane, which could dilate bile canaliculi.     

A Mutant Exhibiting Abnormal Habituation Behavior in Caenorhabditis elegans

The acquisition and retention of information by the nervous system are major processes of learning. Habituation is a simple learning process that occurs during repeated exposure to harmless stimuli. C. elegans is habituated when repeatedly given mechanical stimuli and recover from the habituation when the stimuli are stopped. A habituation abnormal mutant was isolated and assigned to a new gene hab-1 whose mutation causes slow habituation. The hab-1 mutant phenotype is remarkable at short time interval stimuli. However, hab-1 mutant worms show normal dishabituation. Ablations of neurons constituting the neural circuit for mechanical reflexes did not abolish abnormalities caused by the hab-1 mutation.     

TARGETED EXPRESSION OF TEMPERATURE-SENSITIVE DYNAMIN TO STUDY NEURAL MECHANISMS OF COMPLEX BEHAVIOR IN Drosophila

Sites in the brain that show functional, sexual dimorphism in courtship behavior have been mapped at high resolution in male/female mosaics of Drosophila melanogaster. The sex mosaics were produced by enhancer-trap expression of GALA driving the female-spliced form of the transformer gene (tra), revealing sites in the dorsal brain, lateral proto-cerebrum, suboesophageal, thoracic and abdominal ganglia, and suggesting the importance of cross-talk between these regions in the implementation of the courtship sequence.     

Severe autoimmune hemolytic anemia associated with IgM warm auto‐antibodies in primary Sjögren’s syndrome

Primary Sjögren’s syndrome is an autoimmune disorder involving mainly salivary and lachrymal glands. However, many extraglandular symptoms have also been reported. Although leucocytopenia and lymphocytopenia are frequently observed in hematological disorders, autoimmune hemolytic anemia is rarely reported. We experienced a case of primary Sjögren’s syndrome developing severe autoimmune hemolytic anemia. The patient’s red blood cells showed spontaneous agglutination in saline at room temperature, and immunoglobulin M (IgM) was detected on the surface of red blood cells by flow cytometry, indicating that autoimmune hemolytic anemia was caused by warm reactive IgM antibodies. Immediate corticosteroid therapy resulted in a dramatic recovery. We report a first case of severe autoimmune hemolytic anemia caused by warm reactive IgM antibodies in primary Sjögren’s syndrome.