Studies on eleven kidney transplants from non-heart-beating donors

This study was performed to analyze postoperative courses and complications, retrospectively, following transplants from non-heart-beating donors and to examine the correlation between early graft function and clinical parameters. We experienced 11 cases of kidney transplants from non-heart-beating donors during the period from April 1995 to May 2003. Warm ischemic time was less than 30 min in all cases, and total ischemic time ranged from 8.4 hours to 27.9 hours. Rejection reactions occurred in seven cases, two of which were vascular rejections. Infectious disease complications included CMV in two cases, interstitial pneumonia in one case and fungal infection in one case. One patient died from interstitial pneumonia, and three patients had to be restarted on dialysis due to loss of function of the grafted kidney. The remaining seven patients all made full recoveries. All of the 16 patients who underwent living related kidney transplantations during the same period made full recoveries. Both the donor's gender and the latest creatinine level of the donor influenced the posttransplant dialysis period. The posttransplant dialysis period significantly influenced the creatinine level one month after transplant. These results suggest that patients who undergo kidney transplants from non-heart-beating donors have higher rates of complications than patients who undergo living related kidney transplantation. It is important that, in cases where the donor's creatinine level is high, especially when the donor is male, the kidney is carefully retrieved and transported to the recipent hospital to shorten the ischemic period as much as possible.     

Evaluation of multimodality therapy for synchronous liver metastases of gastric cancer

We evaluated the significance of multimodality therapy for cases of liver metastases of gastric cancer. Accumulated survival rate and median survival time were analyzed for twenty cases of such gastric cancer. Survival rates of H1+H2 group and hepatic resection (HR) group were higher than that of H3 group and non-HR group. MST of HR group and hepatic arterial infusion (HAI) group were longer than that of non-HR group and non-HAI group. Survival rate of HAI group was higher than that of non-HAI group among eleven cases of HR group. On the other hand, survival rate of HR group was higher than that of non-HR group among eleven cases of HAI group. These results suggested that HAI chemotherapy after hepatic resection for gastric cancer patients with synchronous liver metastasis would improve prognosis.     

Interaction of G protein beta subunit with inward rectifier K(+) channel Kir3

G protein betagamma subunits bind and activate G protein-coupled inward rectifier K+ (GIRK) channels. This protein-protein interaction is crucial for slow hyperpolarizations of cardiac myocytes and neurons. The crystal structure of Gbeta shows a seven-bladed propeller with four beta strands in each blade. The Gbeta/Galpha interacting surface contains sites for activating GIRK channels. Furthermore, our recent investigation using chimeras between Gbeta1 and yeast beta (STE4) suggested that the outer strands of blades 1 and 2 of Gbeta1 could be an interaction area between Gbeta1 and GIRK. In this study, we made point mutations on suspected residues on these outer strands and investigated their ability to activate GIRK1/GIRK2 channels. Mutations at Thr-86, Thr-87, and Gly-131, all located on the loops between beta-strands, substantially reduced GIRK channel activation, suggesting that these residues are Gbeta/GIRK interaction sites. These mutations did not affect the expression of Gbeta1 or its ability to stimulate PLCbeta2. These residues are surface-accessible and located outside Gbeta/Galpha interaction sites. These results suggest that the residues on the outer surface of blades 1 and 2 are involved in the interaction of Gbetagamma with GIRK channels. Our study suggests a mechanism by which different effectors use different blades to achieve divergence of signaling. We also observed that substitution of alanine for Trp-332 of Gbeta1 impaired the functional interaction of Gbeta1 with GIRK, in agreement with the data on native neuronal GIRK channels. Trp-332 plays a critical role in the interaction of Gbeta1 with Galpha as well as all effectors so far tested.     

The causes of underdiagnosing akathisia

This article reviews what causes clinicians to overlook or underdiagnose akathisia. The causes are considered to be related to both the patient's symptoms and the clinician's attitude toward akathisia. The patient factors include mild severity of akathisia, lack of apparent motor restlessness, no voluntary expression of inner restlessness, no clear communication of inner restlessness, restlessness in body parts other than the legs, atypical expressions of inner restlessness, other prominent psychic symptoms, and absence of other extrapyramidal signs. The clinician factors include emphasis on objective restlessness, failure to consider akathisia during antipsychotic therapy, failure to fully implement antiakathisia treatments in ambiguous cases, and strict adherence to research diagnostic criteria. Akathisia is likely to be overlooked or underdiagnosed when both patient and clinician factors are present. Currently, there may be two major problems with underdiagnosis: (1) symptoms that fulfill the diagnostic criteria for akathisia are overlooked, and (2) conditions that do not fulfill the diagnostic criteria but can still benefit from antiakathisia measures are underdiagnosed.     

Clinical and Radiographic Results for the Richards Modular Hip System Prosthesis in Total Hip Arthroplasty : Average 10-Year Follow-Up

The clinical results of total hip arthroplasty using the Richards Modular Hip System prosthesis were evaluated in 41 patients (44 joints). The mean Harris hip score improved from 42 points before surgery to 82 after 1 year, 85 at 5 years, and 79 at the final examination. The average polyethylene wear rate was 0.09 ± 0.07 mm/y. Forty joints (90.9%) achieved press fit in either of the proximal or the distal stem portion, and only 4 joints (9.1%) failed to achieve press fit in both the proximal and distal stem portions. Although the 10-year survival of the stem was 94.5% and no revisions of the stem were performed, osteolysis was found at high frequency at a distal stem. The high incidence of osteolysis has been the limiting factor in the long-term success of Richards Modular Hip System. Achievement of good canal fill in both the proximal and distal stem portions did not contribute to the good long-term result of the stem.     

FR227244, a novel antifungal antibiotic from Myrothecium cinctum No. 002 Taxonomy, fermentation, isolation and physico-chemical properties

A novel antifungal antibiotic, FR227244, was isolated from the culture broth of a fungal strain No. 002. The strain was identified as Myrothecium cinctum from morphological and physiological characteristics. This compound was isolated from the culture broth by solvent extraction, HP-20 and YMC ODS gel column chromatographies, and n-hexane precipitation. FR227244 is a white powder which melts at 210 to approximately 211 degrees C and possesses the molecular formula C38H58O11. FR227244 is a novel triterpene glycoside with antifungal activity against Aspergillus fumigatus. The effects of FR227244 on the morphology of A. fumigatus were shown to be similar to those of FR901379 which is a known 1,3-beta-glucan synthase inhibitor.     

Estimated Daily Intake and Seasonal Food Sources of Quercetin in Japan

Quercetin is a promising food component, which can prevent lifestyle related diseases. To understand the dietary intake of quercetin in the subjects of a population-based cohort study and in the Japanese population, we first determined the quercetin content in foods available in the market during June and July in or near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained high amounts of quercetin derivatives. We then estimated the daily quercetin intake by 570 residents aged 20–92 years old in the town using a food frequency questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5 mg day⁻¹, respectively. The quercetin intakes by men were lower than those by women; the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer. Our results will help to elucidate the association between quercetin intake and risks of lifestyle-related diseases by further prospective cohort study and establish healthy dietary requirements with the consumption of more physiologically useful components from foods.     

Human adenosine A(3) receptor leads to intracellular Ca(2+) mobilization but is insufficient to activate the signaling pathway via phosphoinositide 3-kinase gamma in mice

Selective antagonists for the adenosine A(3) receptor (A3AR), a member of the G protein-coupled receptors, have been indicated as potential drugs for anti-asthma or anti-inflammation. However, potent antagonists for the rodent A3AR have not been identified. To evaluate the pharmacological effects of human A3AR antagonists in mice, we here generated A3AR-humanized mice, in which the mouse A3AR gene was replaced by its human counterpart. The expression levels of human A3AR in the A3AR-humanized mice were equivalent to those of mouse A3AR in wild-type mice. Elevation of the intracellular Ca(2+) concentration induced by an A3AR agonist was observed in bone marrow-derived mast cells from the A3AR-humanized mice and this Ca(2+) mobilization was completely antagonized by a human A3AR antagonist. However, antigen-dependent degranulation was not potentiated by the A3AR agonist in the mast cells from A3AR-humanized mice. The agonist-stimulated human A3AR did not lead to the phosphorylation of either extracellular signal-regulated kinase 1/2 or protein kinase B in A3AR-humanized mice. The rate of human A3AR internalization in the mast cells was also markedly decreased compared with that of mouse A3AR in the mast cells. These results demonstrate that the human A3AR is insufficient to activate phosphoinositide 3-kinase gamma-dependent signaling pathways in mice, probably due to the uncoupling of member(s) of the G proteins, which are capable of activating phosphoinositide 3-kinase gamma, to the human A3AR, despite the mouse G protein(s) responsible for the Ca(2+) elevation are coupled with the human A3AR.