PubMed Health⌕ Search

Biomedical subjects

T Shimamura

Publications and source records attributed to T Shimamura.

At least 19 recordsLinked to original sources
PubMed2006

Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer.

The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.

Adenocarcinoma↗
PubMed2006

Effects of hepatic CYP3A4 activity on disposition of micafungin in liver transplant recipients with markedly small-for-size grafts.

Micafungin, the first candin antifungal drug developed in Japan, has a significant therapeutic effect against deep-seated mycoses caused by Candida or Aspergillus. Little is known, however, about the optimal dosage or disposition of micafungin in patients with severe hepatic impairment. Nine liver transplant recipients (5 males and 4 females) were enrolled in this study. In 1 recipient with a markedly small-for-size graft (ratio of graft volume to standard liver volume at the time of transplantation: 25.9%), the areas under the plasma concentration-time curves up to 12 hours postdose (AUC(0-12 h)) at doses of 50 and 100 mg/d were 79.38 and 601.17 mug.h/mL, respectively. The corresponding elimination half-life (T(1/2)) values were 16.01 and 75.75 hours, and saturated elimination was observed only at the dose of 100 mg/d. The mean urinary ratio of 6beta-hydroxycortisol to cortisol (6beta-OHF/F) in the small-for-size graft recipient was significantly (P < .05) lower than that in the other recipients. In conclusion, graft size was an important factor affecting disposition of micafungin. For liver transplant recipients with markedly small-for-size grafts, the optimal dosage of micafungin to reach and maintain therapeutic plasma levels is estimated to be 50 mg/d.

Antifungal Agents↗
PubMed2005

Downregulation of inhibitor of apoptosis proteins in apoptotic human chondrocytes treated with tumor necrosis factor-alpha and actinomycin D.

OBJECTIVE: Apoptosis of chondrocytes plays a pivotal role in cartilage degeneration. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine and has been assumed to cause the degradation of human cartilage. To investigate the mechanisms of TNF-alpha-mediated apoptosis of human chondrocytes from a point of view of the balance between the caspase-cascade and the expression of inhibitor of apoptosis proteins (IAPs), although both of them are induced with TNF-signals. METHODS: The expression of TNF-receptors (TNF-Rs) in normal human articular chondrocyte (NHAC-kn) was examined with immunocytochemistry. Subconfluent cultures of NHAC-kn were tested with TNF-alpha and/or actinomycin D (actD), and the induction of apoptosis was evaluated by the frequency of apoptotic cells visualized with nuclear staining using Hoechst 33342. The activation of caspases and the expression of IAPs were examined with Western blot analyses. RESULTS: NHAC-kn expressed TNF-R1 and -R2. When NHAC-kn was treated with TNF-alpha (10 ng/ml) and actD (0.2 microg/ml) for 24 h, the frequency of apoptotic cells increased to more than 25%. TNF-alpha alone, however, induced the apoptosis insufficiently (up to 8.3%), even when used at the concentration of 100 ng/ml for 48 h. In apoptotic human chondrocytes induced with TNF-alpha (10 ng/ml) and actD (0.2 microg/ml), the caspase-3, -8, and -9 were activated and the protein expression of XIAP and c-IAP1 decreased. CONCLUSIONS: In apoptotic human chondrocytes induced with TNF-alpha and actD, the balance between caspase activation and IAPs' expression lay with the executioner caspase (caspase-3) and led to decreased expression of XIAP and c-IAP1.

Apoptosis↗
PubMed2005

Hyaluronic acid diminishes the resistance to excursion after flexor tendon repair: an in vitro biomechanical study.

Adhesion between the tendon and tendon sheath after primary flexor tendon repair is seen frequently, and postoperative finger function is occasionally unsatisfactory. A reduction of the friction may facilitate tendon mobilization, which in turn may reduce the risk of the adhesion and restriction of range of motion. We considered the possibility of utilizing the hyaluronic acid (HA) as a lubricant. To evaluate the effect of HA, the gliding resistance between the canine flexor digitorum profundus tendon repaired by a modified Kessler suture technique with running epitendinous suture and the annular pulley located on the proximal phalanx (corresponding to the A2 pulley in humans) was evaluated and compared before and after administration of HA. The HA solution measurement groups were identified as follows; intact tendon as a control; repaired tendon; tendon soaked in 0.1, 1, and 10 mg/ml HA. The resistance increased after repairing, then it decreased after soaking in 10 mg/ml HA solution. The results of this study revealed that HA diminishes the excursion resistance after flexor tendon repair. We believe that some style of administration of the HA might reduce the excursion resistance and prevent adhesion until the synovial surface is fully developed.

Animals↗
PubMed2005

Juxtacortical chondroma of the hand: treatment by resection of the tumour and the adjacent bone cortex.

A recurrence of a juxtacortical chondroma of the finger after marginal excision prompted us to review the treatment of this condition. Although the recommended treatment is simple curettage or marginal excision, the reported recurrence rate is significantly higher for lesions in the hand than those in other locations and recurrences only occurred in patients who had local treatments which did not include excision of the adjacent bone cortex. We report five patients with juxtacortical chondroma of the fingers. The first patient underwent marginal excision without resection of the underlying bone cortex. The other four patients underwent intralesional, marginal or wide excisions of tumour with resection of the bone cortex underlying the lesion. Recurrence was only seen in the patient who did not undergo resection of the bone cortex. Resection of the underlying bone cortex after excision of this tumour may be advisable for the treatment of this tumour in the hand to reduce the rate of recurrence.

Adolescent↗
PubMed2004

Effect of hyaluronic acid on the excursion resistance of tendon grafts. A biomechanical study in a canine model in vitro.

The excursion resistance between the tendon and pulley is an important factor contributing to the limitation of function after surgery to the hand. The administration of hyaluronic acid (HA) in the early rehabilitation after tendon grafting may help to prevent adhesions. We evaluated changes in the excursion resistance between potential sources of flexor tendon grafts and the annular pulley in a canine model after administration of HA. The intrasynovial and extrasynovial tendons were soaked in 10 mg/ml of HA for five minutes. The excursion resistance between these tendons and the annular pulley of an intact proximal phalanx and that of the same tendons of the opposite foot without administration of HA were evaluated. The tendon of flexor digitorum profundus of the second toe without administration of HA was used as a control. The gliding resistance of canine tendons was significantly decreased after the administration of HA especially in the extrasynovial tendons. Our findings suggest that the administration of HA may improve the gliding function of a flexor tendon graft.

Adjuvants, Immunologic↗
PubMed2003

No major tumorigenic role for beta-catenin in serrated as opposed to conventional colorectal adenomas.

Intracellular redistribution of beta-catenin through mutation of the adenomatous polyposis coli (APC) gene has been proposed as an early tumorigenic event in most colorectal tumours. In serrated adenoma (SA), a newly recognised subtype of colorectal adenoma, APC mutations are uncommon, and the contribution of beta-catenin to tumorigenesis remains unclear. We compared intracellular localisation of beta-catenin and presence of mutations in exon 3 of beta-catenin between 45 SAs, with 71 conventional adenomas (CADs), and eight carcinomas invading the submucosa (SCAs). Widespread or focal nuclear beta-catenin expression was demonstrated in 7% of SAs (three out of 45), 61% of CADs (43 out of 71), and 88% of SCAs (seven out of eight). Cytoplasmic immunostaining for beta-catenin was demonstrated in 16% of SAs (seven out of 45), 77% of CADs (55 out of 71), and 88% of SCAs (seven out of eight). No mutation in exon 3 of beta-catenin was found in SAs or SCAs, while 7% of CADs (five out of 71) had beta-catenin mutations. No nuclear or cytoplasmic expression of beta-catenin was observed in the hyperplastic or conventionally adenomatous epithelium of mixed-type SAs. These findings suggest that beta-catenin mutation is unlikely to contribute to the tumorigenesis in SA, and that intracellular localisation of beta-catenin may not be associated with an early event of the tumour progression in most SAs.

Adenoma↗
PubMed2003

Prognostic significance of dysadherin expression in advanced colorectal carcinoma.

A novel glycoprotein, dysadherin, has an anti-cell - cell adhesion function through downregulating E-cadherin. In this study, we investigated the expressions of dysadherin and E-cadherin in 82 patients with stage II and III colorectal carcinomas to determine the correlation between the two molecules and the clinicopathologic features of each tumour. Dysadherin was not expressed in normal colorectal epithelium. Fifty-one per cent of tumours showed dysadherin immunopositivity in over 50% of cancer cells. Thirty-eight per cent of tumours showed reduced E-cadherin immunopositivity. The increased expression of dysadherin was significantly associated with lung metastasis (P=0.003). The increased expression of dysadherin had a significant impact on patient survival (P=0.0099 and 0.0036, log-rank test for overall and recurrence-free survival rate, respectively). Furthermore, tumour with increased expression of dysadherin and reduced expression of E-cadherin showed the worst prognosis (P=0.0043 and 0.0028, log-rank test for overall and recurrence-free survival rate, respectively). These results suggest that increased dysadherin expression is a significant indicator of poor prognosis for patients with advanced colorectal carcinoma.

Aged↗
PubMed2003

Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of tacrolimus in liver transplant recipients with small-for-size grafts.

In adult-to-adult living donor liver transplantation (LDLT), the graft volume is inevitably much smaller than the ideal liver mass (standard liver volume) for the recipient's metabolic demand. Patients with small-for-size grafts are treated with continuous venovenous haemodiafiltration (CVVHD) for the artificial liver support. However, little is known about the influence of CVVHD on the elimination of tacrolimus. The objective of this study was to elucidate the effect of CVVHD on the pharmacokinetics of tacrolimus in recipients of LDLT with small-for-size grafts. Three liver transplant recipients (one male and two females) and donors (two males and one female) were enrolled in this study. Blood samples from inflow port and outflow port were obtained on the first day at the start of CVVHD. Whole-blood concentrations of tacrolimus were measured immediately using the microparticle enzyme immunoassay (MEIA; Abbott Laboratories). There was no significant difference between concentrations of tacrolimus in blood sampled at inflow port and outflow port sites and t(1/2)-values of tacrolimus in the three recipients were 29.9, 63.6 and 28.8 h. CVVHD did not cause a decrease in the blood tacrolimus concentration. Adjustment to the dose or dosing interval is not required for patients treated with tacrolimus during CVVHD.

Adult↗
PubMed2003

Restoration of antibacterial activity of beta-lactams by epigallocatechin gallate against beta-lactamase-producing species depending on location of beta-lactamase.

The combined effects of (-)-epigallocatechin gallate (EGCg) and beta-lactams were investigated against various beta-lactamase-producing clinical isolates, including 21 Staphylococcus aureus, 6 Escherichia coli, 3 Klebsiella pneumoniae and 8 Serratia marcescens strains. Penicillin in combination with EGCg at 12.5 microg mL(-1) showed the most potent synergy against 100% penicillinase-producing S. aureus. However, cefotaxime or imipenem in combination with higher concentration of EGCg (100 microg mL(-1)) only showed slight synergy against 2 of 17 Gram-negative rods. Similar to the effect on the penicillinase from S. aureus, however, EGCg also directly inhibited the extracted beta-lactamases from the Gram-negative rods, thereby protecting beta-lactams from inactivation. The different effects of the combinations on different beta-lactamase-producing species were confirmed to be related to the cellular locations of beta-lactamases. In contrast to a 32.7% extracellular fraction of total beta-lactamase activity in a penicillinase-producing S. aureus, the fractions were 0.6%, 0.6% and 1.2% in a TEM-derived extended-spectrum beta-lactamase-producing E. coli, an inhibitor-resistant beta-lactamase-producing K. pneumoniae and an IMP-producing S. marcescens, respectively. In conclusion, the combination of penicillin with EGCg showed potent synergy against penicillinase-producing S. aureus in-vitro. The combinations of beta-lactams and EGCg against beta-lactamase-producing Gram-negative rods do indicate a limitation owing to the cellular location of beta-lactamases.

Anti-Bacterial Agents↗
PubMed2002

Postoperative outcome of lumbar spinal canal stenosis after fenestration: correlation with changes in intradural and extradural tube on magnetic resonance imaging.

PURPOSE: To evaluate the serial changes in clinical results and the intradural and extradural spaces on magnetic resonance imaging (MRI) after bilateral fenestration in 48 patients with lumbar spinal canal stenosis (LSCS). METHODS: A prospective interventional study was performed to study the clinical results, magnetic resonance imaging scans among patients who were followed up for more than 3 years. RESULTS: All patients showed improvement in clinical symptoms after operation, but clinical results deteriorated in 9 (19%) patients. Postoperative MRI scans showed that poor dural tube expansion, grouping of the cauda equina, and decrease in the cross-sectional area of the dural tube were factors associated with poor outcomes. The cross-sectional area of the dural tube and images of the cauda equina observed by MRI, before and after fenestration and during follow-up, reflected changes in clinical symptoms involving decompressed segments. CONCLUSION: Serial changes in the cross-sectional area of the dural tube and images of the cauda equina observed preoperatively, postoperatively, and on follow-up by MRI may be useful when evaluating patients' condition before and after operation. It is also useful for predicting outcomes.

Aged↗
PubMed2001

Protective effect of agiotensin II type I receptor antagonist, CV-11974, on ischemia and reperfusion injury of the liver.

BACKGROUND: Microcirculatory disturbance has been shown to play a critical role in hepatic ischemia and reperfusion (I/R) injury. Angiotensin II (AngII) is one of the most potent endogenous vasoconstrictors. Angiotensin II type I (AT1) receptor antagonist has been reported to have protective effects on I/R injury of the heart and kidney. However, effect on hepatic I/R injury has not been determined. In this study, we investigate our hypothesis that AT1 receptor antagonist, CV-11974, attenuates hepatic I/R injury. METHODS: Twelve beagle dogs underwent a 2-hr total hepatic vascular exclusion with veno-venous bypass. CV-11974 was given to animals at a dose of 0.002 mg/ kg/min for 5 min followed by 0.001 mg/kg/min for 25 min via portal vein before ischemia (group II, n=6). Nontreated animals were used as the control (group I, n=6). Animal survival, hemodynamics, hepatic tissue blood flow (HTBF), liver function, platelet count, renin activity, and AngII concentration of hepatic vein, energy metabolism, and histopathology were analyzed. RESULTS: Two-week survival was 33% in group I, in contrast, 100% in group II. Mean arterial blood pressure during early reperfusion was maintained, and HTBF after reperfusion was significantly higher in group II. Treatment attenuated liver enzyme release and decrease of platelet count, increased renin and AngII, suppressed ATP degradation during ischemia and enhanced ATP resynthesis after reperfusion. Neutrophil infiltration and histopathological damages were lessened in group II. CONCLUSIONS: Our data demonstrated that the local renin-angiotensin system might play a role in hepatic microcirculation. AT1 receptor blockade with CV-11974 attenuated hepatic microcirculatory disturbance and ameliorated I/R injury.

Angiotensin II↗
PubMed2001

Attenuation of ischemia and reperfusion injury of canine livers by inhibition of type II phospholipase A2 with LY329722.

BACKGROUND: Membrane phospholipid breakdown, caused by ischemia and reperfusion (I/R) of the liver, releases free fatty acids including arachidonic acids and lysophospholipids, which serve as precursors of various inflammatory lipid derivatives. Phospholipase A2 (PLA2) is a key enzyme that initiates this reaction. In this study, we tested our hypothesis that a type II PLA2 inhibitor, LY329722, could attenuate hepatic I/R injury caused by a 2-hr total hepatic vascular exclusion (THVE) in dogs. METHODS: Eighteen beagle dogs, subjected to a 2-hr THVE, were divided into three groups. Group 1 (n=6) was untreated and served as a control group. LY329722 was administered to animals in group 2 (n=6) intravenously (0.2 mg x kg(-1) x hr(-1)) for 60 min before ischemia, and to animals in group 3 (n=6) for 60 min starting 15 min before reperfusion (0.2 mg x kg(-1) x hr(-1)). Animal survival, systemic and splanchnic hemodynamics, hepatic tissue blood flow, liver functions, energy metabolism, hepatic venous thromboxane B2 and endothelin-1 levels, phospholipid levels and tumor necrosis factor-a mRNA expression in liver tissue, and histopathologic findings were evaluated. RESULTS: Two-week animal survival was 33% (two of six) in group 1, and 100% (six of six) in groups 2 and 3. LY329722 improved systemic and splanchnic hemodynamics, hepatic tissue blood flow, and energy metabolism, reduced liver enzyme, thromboxane B2, and endothelin-1 release, prevented hepatic phospholipid degradation and tumor necrosis factor-alpha mRNA expression, and lessened histopathologic damage and the number of neutrophil infiltrating into the liver tissue. CONCLUSION: The present study demonstrated that a type II PLA2 inhibitor, LY329722, attenuated hepatic I/R injury caused by a 2-hr THVE model in dogs.

Acetates↗
PubMed2001

Cervical spine injury in the elderly: imaging features.

An increase in the elderly population has resulted in an increased incidence of cervical spine injury in this group. No specific type of cervical spine trauma is seen in the elderly, although dens fractures are reported to be common. Hyperextension injuries due to falling and the resultant central cord syndrome in the mid and lower cervical segments due to decreased elasticity as a result of spondylosis may be also characteristic. The imaging features of cervical spine injury are often modified by associated spondylosis deformans, DISH and other systemic disorders. The value of MR imaging in such cases is emphasized.

Aged↗
PubMed2001

Survival-associated histologic spreading modes of operable intrahepatic, peripheral-type cholangiocarcinomas.

We investigated survival-associated histologic and metastatic spreading modes of intrahepatic, peripheral-type cholangiocarcinomas resected to contribute to surgical control of the tumor. Previous results have been mostly obtained from autopsies, reflecting the terminal status of patients. We clinicopathologically reviewed the resected 20 intrahepatic, peripheral-type cholangiocarcinomas and investigated the histologic findings of resected specimens and medical records to assess spreading modes along with patients' survival. The carcinoma cells superficially spread in the ductal epithelium in 75%, infiltrated along Glisson's system and migrated multidirectionally in 100%, and permeated the vascular network in 80%. The cumulative survival rate significantly related to vascular permeation, extrahepatic metastases, and lymphatic, neural, and nodal involvement but not to ductal spread, tumor size (cutoff size 5 cm), or intrahepatic metastases by the log-rank test. The patients with lymphatic, neural, or nodal involvement died early after surgery. Practically, only vascular permeation was identified as a significant independent variable for survival using multivariate analysis. Peripheral cholangiocarcinomas spread mainly in three modes: ductal spread, infiltration along Glisson's system, and vascular permeation. In the practically operable cases, vascular permeation is closely related to survival, and intrahepatic metastasis may be surgically controlled to some degree.

Aged↗
PubMed2001

Inhibition by epigallocatechin gallate (EGCg) of conjugative R plasmid transfer in Escherichia coli.

Epigallocatechin gallate (EGCg) in tea catechins blocked or significantly diminished the transfer of conjugative R plasmid between Escherichia coli C600 with plasmid R-222 (donor) and E. coli K-12 RC85 (recipient) in a dose-dependent manner. The inhibition rates of R plasmid transfer by EGCg were 42%-67% at 50-200 microg/ml, and up to 99% at 800 microg/ml. Nevertheless, EGCg, even at the concentration of 1600 microg/ml, was not sufficient to kill E. coli cells in 1 h, as confirmed by determining viable cells after incubation with various concentrations of EGCg. The result indicates that the bactericidal activity of EGCg against the two strains was not the main factor responsible for the inhibition of R plasmid transfer. This observation suggests the possibility that tea consumption may be effective in preventing R plasmid transfer in enteric bacteria.

Catechin↗