Prebiotic effect of galacto-N-biose on the intestinal lactic acid bacteria as enhancer of acetate production and hypothetical colonization.

Galacto-N-biose (GNB) is an important core structure of glycan of mucin glycoproteins in the gastrointestinal (GI) mucosa. Because certain beneficial bacteria inhabiting the GI tract, such as bifidobacteria and lactic acid bacteria, harbor highly specialized GNB metabolic capabilities, GNB is considered a promising prebiotic for nourishing and manipulating beneficial bacteria in the GI tract. However, the precise interactions between GNB and beneficial bacteria and their accompanying health-promoting effects remain elusive. First, we evaluated the proliferative tendency of beneficial bacteria and their production of beneficial metabolites using gut bacterial strains. By comparing the use of GNB, glucose, and inulin as carbon sources, we found that GNB enhanced acetate production in Lacticaseibacillus casei, Lacticaseibacillus rhamnosus, Lactobacillus gasseri, and Lactobacillus johnsonii. The ability of GNB to promote acetate production was also confirmed by RNA-seq analysis, which indicated the upregulation of gene clusters that catalyze the deacetylation of N-acetylgalactosamine-6P and biosynthesize acetyl-CoA from pyruvate, both of which result in acetate production. To explore the in vivo effect of GNB in promoting acetate production, antibiotic-treated BALB/cA mice were administered with GNB with L. rhamnosus, resulting in a fecal acetate content that was 2.7-fold higher than that in mice administered with only L. rhamnosus. Moreover, 2 days after the last administration, a 3.7-fold higher amount of L. rhamnosus was detected in feces administered with GNB with L. rhamnosus than in feces administered with only L. rhamnosus. These findings strongly suggest the prebiotic potential of GNB in enhancing L. rhamnosus colonization and converting L. rhamnosus into higher acetate producers in the GI tract. IMPORTANCE: Specific members of lactic acid bacteria, which are commonly used as probiotics, possess therapeutic properties that are vital for human health enhancement by producing immunomodulatory metabolites such as exopolysaccharides, short-chain fatty acids, and bacteriocins. The long residence time of probiotic lactic acid bacteria in the GI tract prolongs their beneficial health effects. Moreover, the colonization property is also desirable for the application of probiotics in mucosal vaccination to provoke a local immune response. In this study, we found that GNB could enhance the beneficial properties of intestinal lactic acid bacteria that inhabit the human GI tract, stimulating acetate production and promoting intestinal colonization. Our findings provide a rationale for the addition of GNB to lactic acid bacteria-based functional foods. This has also led to the development of therapeutics supported by more rational prebiotic and probiotic selection, leading to an improved healthy lifestyle for humans.

An Autopsy Case of Pulmonary Capillary Hemangiomatosis with an Electron Microscopy Study.

BACKGROUND Pulmonary capillary hemangiomatosis (PCH) and pulmonary veno-occlusive disease (PVOD) are rare diseases that share clinical, X-ray, and histological features. Most patients have poor prognosis due to severe respiratory impairment. Recently, EIF2AK4 mutations were found in some patients with PCH and PVOD, but the role of this mutation is still unknown. We report an autopsy case of PCH and discuss a mechanism of respiratory dysfunction based on an electron microscopy study. CASE REPORT The patient was a Japanese man in his sixties. He suffered from acute exacerbation of dyspnea during treatment of COPD. Respiratory function testing revealed DLCO' 32.1% and DLCO'/VA 23.6%. Echocardiography demonstrated findings consistent with pulmonary hypertension. A CT scan showed mild emphysema and small ground-glass opacity in the lungs. However, we could not find the exact cause of his respiratory failure and he died 28 days after admission. At autopsy, the histology showed multilayering capillary proliferation within the alveolar walls. Electron microscopy examination revealed prominent widening of the air-blood barrier, scarce fusion of the epithelial and capillary basement membranes, and frequent narrowing of the capillary lumen. CONCLUSIONS We reported an autopsy case with PCH with no histological findings of PVOD. Whether PCH and PVOD are 2 different histological patterns of the same disease remains to be verified. The changes in the air-blood barrier detected by electron microscopy may explain the respiratory impairment and pulmonary arterial hypertension.

AS1949490, an inhibitor of 5'-lipid phosphatase SHIP2, promotes protein kinase C-dependent stabilization of brain-derived neurotrophic factor mRNA in cultured cortical neurons.

Brain-derived neurotrophic factor (BDNF), an essential factor for maintaining brain functions, has been reported to be reduced in various neurological diseases, including Alzheimer's disease and major depression. Therefore, new drugs to increase the BDNF expression need to be developed. Since phosphatidylinositol (3,4,5)-trisphosphate, a membrane signaling molecule produced by phosphoinositide 3 (PI3)-kinase in the BDNF signaling, is a candidate target of SH2 domain-containing inositol 5' phosphatase 2 (SHIP2, a 5'-lipid phosphatase), the present study examined the effect of a SHIP2 inhibitor AS1949490 on Bdnf expression in cultured cortical neurons. BDNF increased its own mRNA levels, and AS1949490 enhanced this positive feedback regulation. The effects of BDNF in combination with AS1949490 on the Bdnf mRNA levels were blocked by inhibitors of mitogen-activated protein kinase kinase (U0126), PI3-kinase (LY294002), phospholipase Cγ (U73122), and protein kinase C (bisindolylmaleimide I), whereas the effect of BDNF alone was inhibited only by U0126. The mRNA stability assay using actinomycin D demonstrated that AS1949490 reduced degradation of the self-amplified Bdnf mRNA levels, and this effect was disappeared in the presence of bisindolylmaleimide I. These results suggest that BDNF promoted the Bdnf mRNA stabilization in a protein kinase C-dependent manner only in the presence of AS1949490, thereby enhancing Bdnf expression. Furthermore, behavioral analyses indicated that central administration of AS1949490 caused memory-improving and anti-depressant effects in passive avoidance test and forced swim test, respectively. Therefore, inhibition of SHIP2 appears to be valuable therapeutic strategy against neurological disorders associated with insufficient BDNF functions.

[A case of non-small cell lung cancer treated safely by whole brain radiation therapy and erlotinib].

In December 2006, a 55-year-old-man was given a diagnosis of adenocarcinoma of the lung with multiple brain metastases. Systemic chemotherapy was given consisting of carboplatin plus paclitaxel and carboplatin plus gemcitabine. But with the increase of the brain metastases, he was admitted in February 2008. He received whole brain radiation therapy and was given erlotinib at the same time. The brain metastases disappeared and primary lung tumor decreased after the start of therapy. No side effect was observed. Although further investigations are needed to completely determine the efficacy of this treatment procedure, it seems clear that combining erlotinib with radiation therapy produces a synergy effect on the cancer.

[Severe case of Tsutsugamushi disease with disseminated intravascular coagulation and acute respiratory distress syndrome].

A 65-year-old man was admitted because of high grade fever and cough after 3 days of gathering edible wild plants. Although ceftriaxone was given to him, his symptoms did not improve. His high grade fever escalated after changing the antibiotics (imipenem with erythromycin). His situation further declined with disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). As a result, he was transferred to the Department of Respiratory Medicine 7 days after admission. He was intubated and placed on mechanical ventilation and treated by polymyxin-direct hemoperfusion. The eschar on his chest wall caused us to suspect Tsutsugamushi disease and a blood test confirmed our suspicion. Since the antibodies for Tsutsugamushi were elevated we arrived at the diagnosis of Tsutsugamushi disease with DIC and ARDS. The administration of tetracycline was sufficient to significantly improve his condition. Because its complications are life threatening, when we see a patient with fever and eruptions, it is necessary to keep in mind the possibility of Tsutsugamushi disease. Careful anamnesis and physical examinations are most important for the diagnosis of Tsutsugamushi disease.

[Isolation-frequency and antibiotic susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa isolated in regional core hospitals in the Nagaoka district of Niigata Prefecture (changes for 3 years)].

We measured MICs of various antimicrobial agents against Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa isolated in the Nagaoka district of Niigata Prefecture in 2000 (March-May), 2001 (January-May), and 2002 (March-May). S. pneumoniae: Fifty-six strains were isolated in 2000, 119 strains in 2001, and 88 strains in 2002. In 2000, 2001, and 2002, 24 strains (42.9%), 58 strains (48.7%), and 40 strains (45.5%), respectively, were penicillin-intermediate S. pneumoniae (PISP), and 4 strains (7.1%), 12 strains (10.1%), and 7 strains (8.0%), respectively, were penicillin-resistant S. pneumoniae (PRSP). Carbapenems had the most excellent antimicrobial activity, followed by penicillin G, against penicillin-susceptible S. pneumoniae (PSSP), PISP, and PRSP. H. influenzae: Seventy-six strains were isolated in 2000, 154 strains in 2001, and 91 strains in 2002. In 2000, 2001, and 2002, 6 strains (7.9%), 8 strains (5.2%), and 7 strains (7.7%), respectively, were beta-lactamase-producing ampicillin (ABPC)-resistant strains (MIC > or = 2 micrograms/ml), showing no increase, and 14 strains (18.4%), 70 strains (45.5%), and 31 strains (34.1%), respectively, were beta-lactamase-non-producing ABPC-resistant strains (MIC > or = 2 micrograms/ml), showing a slight increase. Ceftriaxon, meropenem (MEPM), and levofloxacin had excellent antimicrobial activity against these resistant strains. P. aeruginosa: In 2000, 2001, and 2002, 135, 74, and 91 strains, respectively, were isolated, and 14 strains (10.4%), 17 strains (23.0%), and 24 strains (26.4%), respectively, were imipenem-resistant (MIC > or = 16 micrograms/ml), showing a slight increase. MEPM, biapenem, and ciprofloxacin had excellent antimicrobial activity against P. aeruginosa.

Field survey of Glycyrrhiza plants in central Asia (2). Characterization of phenolics and their variation in the leaves of Glycyrrhiza plants collected in Kazakhstan.

A new prenylated flavanone, licoleafol, and a new prenylated dihydrostilbene, uralstilbene, together with four known compounds, 8-dimethylallyleriodictyol, sophoraflavanone B, gancaonin R, and 6-dimethylallyleriodictyol, were isolated from the leaves of Glycyrrhiza uralensis collected in Kazakhstan. HPLC analysis of the leaves of Glycyrrhiza plants collected in Kazakhstan showed that both G. uralensis-specific and Glycyrrhiza glabra-specific compounds were detected in the leaves of the morphologically intermediate-type plants, suggesting that the intermediate-type plant is a hybrid of G. glabra and G. uralensis. In addition, HPLC profiles of leaf extracts from offspring of intermediate-type plants were divided into the three types: the G. uralensis type, G. glabra type, and the intermediate type. From these results, it appears likely that the intermediate-type plant back-crosses with G. glabra and G. uralensis to generate a G. glabra-type plant and a G. uralensis-type plant, respectively.