ATP-dependent glucokinase is suggested to have evolved from a hypothetical polyphosphate (polyP)-dependent glucokinase (polyP-GK) via a bifunctional polyP/ATP glucokinase (polyP/ATP-GK). Here we showed that polyP-GK is present in a polyP-accumulating bacterium, Microlunatus phosphovorus. The polyP-GK produced glucose-6-P i from glucose and polyP, but it could not phosphorylate glucose with ATP. The polyP-GK was most closely related to the polyP/ATP-GK of Mycobacterium tuberculosis.Inorganic polyphosphate (polyP) is a linear polymer of tens or hundreds of orthophosphate (P i ) residues linked in the same manner as the two high-energy phosphoanhydride bonds in ATP (4, 5). PolyP is readily formed by dehydration of P i and found in abundance in volcanic condensates and deep-oceanic steam vents (14). Hence, ancient organisms may have utilized polyP instead of ATP in their metabolic reactions (4,9,14).Glucokinases that use ATP as the sole phosphoryl donor to catalyze the phosphorylation of glucose (ATP-GKs) have been present in all contemporary organisms examined (2). Bifunctional glucokinase (polyP/ATP-GK), which utilizes polyP or ATP as the phosphoryl donor to phosphorylate glucose, was found first in Mycobacterium phlei (10) and then in many other bacteria, including Corynebacterium diphtheriae (11), Mycobacterium tuberculosis (12), and Propionibacterium shermanii (13). The polyP/ATP-GK of M. tuberculosis also utilizes GTP, UTP, and CTP as phosphoryl donors (12). PolyP is recognized as one of the earliest biopolymers and is most likely a prominent precursor in prebiotic evolution (4). Thus, it has been hypothesized that glucose phosphorylation was originally mediated by polyP and that when ATP became available in the environment, a transition was made by the GKs to utilize the latter phosphoryl donor (9). However, nobody has discovered the strictly polyP-dependent glucokinase that utilizes polyP as the sole phosphoryl donor (polyP-GK).Microlunatus phosphovorus strain NM-1 is a gram-positive, coccus-shaped, non-spore-forming bacterium (7). Strain NM-1, which was originally isolated with an enhanced biological phosphorus removal process, accumulates large amounts of polyP (a maximum of approximately 48% of its dry weight as phosphate [P i ]) in a glucose medium (7). We discovered the existence of polyP-GK in M. phosphovorus strain NM-1.M. phosphovorus strain NM-1 was grown for 2 days under aerobic conditions at 27°C in the glucose medium (7). The cells harvested at the mid-logarithmic phase of growth were disrupted by using Bead-beater (Biospec), and the polyP-GK was precipitated by adding 70% ammonium sulfate. The polyP-GK was further purified by using a DEAE-cellulose (Whatman), a phenyl-Sepharose (Amersham Biosciences), a PE hydrophobic (Poros), and two anion exchange (HQ [Poros] and miniQ [Amersham Biosciences]) columns. The polyP-GK was purified 253-fold (Fig. 1A), and the recovery of polyP-GK activity was 6.7%. The polyP-GK migrated as a 32-kDa protein on sodium dodecyl sulfate (SDS)-polyacrylamide gels, while...

Summary Background : The incidence and severity of non‐steroidal anti‐inflammatory drugs (NSAIDs)‐induced gastro‐duodenal ulcer have not been extensively studied in Japan. Aim : We performed a prospective study to clarify NSAIDs‐induced gastro‐duodenal injury, focusing especially on low‐dose aspirin (L‐A). Methods : Two hundred and thirty‐eight patients with bleeding peptic ulcers admitted to our hospital. History of taking NSAIDs and anti‐ulcer drugs was obtained from all patients who underwent endoscopic examinations. The lesion scores of patients taking L‐A were classified numerically from zero (no lesion) to five (ulcer). Results : The NSAIDs were associated with 28.2% of hemorrhagic ulcers. The rates of patients using L‐A, loxoprofen, diclofenac, and combination of two of these drugs were 27, 16, 10 and 9%, respectively. Co‐administered anti‐ulcer drugs were cytoprotective anti‐ulcer drugs (27%), H2 receptor antagonists (16%), PPI (4%), and none (53%). In patients taking L‐A, H2 receptor antagonists were used most frequently. The HP was positive in 63% of L‐A‐induced ulcer cases and in 69% of NSAIDs other than low‐dose aspirin‐induced ulcer cases. The lesion scores of patients taking L‐A with H2 receptor antagonists or PPI were significantly lower than those of patients who were taking only L‐A (P < 0.05). Conclusions : Approximately one‐third of hospitalized patients with NSAIDs‐induced hemorrhagic ulcer showed an association with L‐A. Prospective randomized controlled trials including H2 receptor antagonists are required to establish preventive efforts aimed at L‐A‐induced gastro‐duodenal injury.

Bleeding from rectal varices was controlled satisfactorily by the therapeutic strategy of selecting EVL, EIS or B-RTO as an additional therapy according to the size and hemodynamics of the varices.

Miriplatin is a useful and safe agent for TACE in patients with HCC stage I or II and/or JIS score 0 or 1 only when radiofrequency ablation and liver resection cannot be performed.

For HCC patients, although miriplatin-TACE was superior to epirubicin-TACE in the short term, it proved inferior to the latter in the long term. The merits of TACE using miriplatin should be further investigated, because adverse effects appear to be minimal after miriplatin administration.