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Biomedical subjects

K Miwa

Publications and source records attributed to K Miwa.

At least 109 records · Page 6Linked to original sources
PubMed1999

Analysis of paraaortic lymph node involvement in pancreatic carcinoma: a significant indication for surgery?

BACKGROUND: Lymph node status is a key prognostic factor for pancreatic carcinoma. The paraaortic lymph nodes are the highest level of lymph nodes that can be resected safely in the abdomen for pancreatic and other gastrointestinal tumors. The pattern of paraaortic lymph node involvement and its relation with other lymph node groups were analyzed and the significance of this information relative to surgical therapy examined. METHODS: Between 1974-1996, 99 patients with invasive ductal carcinoma of the pancreas underwent pancreatectomy at the study institution. The pattern of lymph node involvement, particularly paraaortic, was evaluated by careful pathologic review of extended lymphadenectomy specimens. RESULTS. Fifty-eight of 76 patients (76%) with carcinoma in the pancreatic head (Ph) and 19 of 23 patients (83%) with carcinoma of the pancreatic body and tail (Pbt) had lymph node involvement. Fourteen patients with Ph disease (18%) and 4 with Pbt disease (17%) had paraaortic lymph node involvement. Tumor size did not correlate with paraaortic lymph node involvement. A correlation was found between Group 13 (posterior pancreaticoduodenal lymph nodes), Group 14 (lymph nodes surrounding the superior mesenteric artery), and the paraaortic lymph nodes for Ph disease. All paraaortic lymph node metastases were located in the 16M region (the region between the celiac trunk and the inferior mesenteric artery). For patients with Pbt disease, the distribution of paraaortic lymph node metastases was the same as for those with Ph disease. Only 33% of cases of paraaortic lymph node metastases were suspected preoperatively or perioperatively. The longest survival for a patient with paraaortic lymph node metastases was 36 months and 17 months, respectively, for patients with Ph and Pbt disease. CONCLUSIONS: The paraaortic lymph nodes are frequent sites of metastasis from pancreatic carcinoma, and are difficult to evaluate preoperatively or perioperatively. This situation mandates paraaortic lymph node dissection, at least in the 16M region.

Adult↗
PubMed1999

The Outcome of Patients with Breast Cancer Who Underwent Breast Conserving Treatment with or without Immediate Volume Replacement with Autogenous Tissue.

BACKGROUND: Breast conserving treatment (BCT) is accepted as an appropriate therapy for most patients with stage I and stage II breast cancer. However, BCT is associated with a relatively high incidence of local recurrence, and aesthetically unacceptable results occur in some patients. A novel method of immediate volume replacement using autogenous tissue has been developed to strike a balance between adequate excision and cosmesis. We determined the oncological outcome inpatients with breast cancer treated with wide excision, immediate volume replacement with autogenous tissue, and axillary dissection followed by radiotherapy. METHODS: One hundred fifty-three patients with TIS, stage I, II, or III breast cancer underwent wide excision and axillary dissection. The surgical margin ofexcised breast tissue was examined histologically during surgery. If involved, the breast tissue adjacent to the primary site was excised. When the margin of re-excision was positive, patients underwent modified radical mastectomy with or without breast reconstruction. After wide excision, immediate volume replacementwith autogenous tissue was perform-ed, unless the deformity was corrected by undermining and conization of the residual breast tissue. Postoperatively, all patients received breast irradiation. RESULTS: Eighteen patients underwent modified radical mastectomy. The surgical margin was negative in 132 of the 135 patients who underwent BCT. The crude local recurrence rate was 0.7% (1/135). Estimated overall and disease-free 5-year survival rates were 96% and 94%, respectively. CONCLUSION: Wide excision with tumor-free margins and axillary dissection followed by breast irradiation provides adequate local control in many patients with breast cancer. Immediate breast volume replacement with autogenous tissue mayavoid some unpleasant cosmetic results associated with extensive local resection. Our technique eliminates the need for mastectomy in selected patients.

Journal Article↗
PubMed1999

Possible factor for nonlinear pharmacokinetics of TAK-603, a new antirheumatic agent, in rats.

A new antirheumatic, TAK-603, shows nonlinear pharmacokinetics in both animals and humans. To elucidate the mechanism of these nonlinear pharmacokinetics, in vivo and in vitro metabolism of 14C-labeled TAK-603 ([14C]TAK-603) was studied using rats as these resemble humans in their metabolic profiles. After intravenous injection of [14C]TAK-603 to rats at doses of 1, 5, and 15 mg kg(-1), the total body clearance of unchanged drug decreased significantly with increasing dose, whereas the apparent distribution volume did not alter remarkably. Thus, saturation in the elimination processes was considered to be a factor responsible for the nonlinear pharmacokinetics. The disappearance of unchanged drug from the circulation, however, followed a dose-dependent first-order process, indicating that the nonlinearity observed was not merely due to saturation of the elimination capacity. In vitro studies using rat liver microsomes showed that TAK-603 competitively inhibited CYP-catalysed nifedipine oxidation and also that the demethylated metabolite M-I, the major metabolite in rats and humans, competitively inhibited the oxidation of nifedipine. These results suggested that inhibition by M-I of the metabolism of the parent drug (i.e. product-inhibition) may be the most likely factor responsible for the nonlinear pharmacokinetics of TAK-603.

Administration, Oral↗
PubMed1999

Comparison of pathogenic factors expressed by group A Streptococci isolated from patients with streptococcal toxic shock syndrome and scarlet fever.

Streptococcal toxic shock syndrome (STSS) is an illness with high mortality. To obtain clues to understanding the pathogenesis of STSS, we investigated the expression of several pathogenic factors in ten group A streptococcus (GAS) isolates from ten patients with STSS in Japan, in comparison with ten GAS isolates from children with scarlet fever. The ten scarlet fever-derived GAS isolates were equally low in lethality and anti-phagocytic activity in mice and in the production of streptolysin O (SLO), and equally high in production of superantigenic exotoxins (SAGTs) and cysteine proteinase. By comparison, the ten STSS-derived GAS isolates were heterogeneous in the expression of the above pathogenic factors, which ranged from low to high values. Most of the ten STSS-derived isolates were higher in lethality and anti-phagocytic activity and production of SLO, and lower in the production of SAGTs and cysteine proteinase than the ten scarlet fever-derived isolates. The results suggest that the lethality and anti-phagocytic activity examined in mice and SLO may be involved mainly in the development of most of the ten STSS cases.

Animals↗
PubMed1999

Complications associated with enteral nutrition using catheter jejunostomy after esophagectomy.

The present study was conducted on 78 patients, encountered over a 7-year period, who had a catheter-feeding jejunostomy placed at the time of thoracoabdominal esophagectomy for esophageal cancer. A broad-based attachment of the jejunal wall to the peritoneum at the place of entry of the catheter was used. Enteral nutrition was begun an average of 10 days after the operation, the caloric content was increased gradually, and the mean duration was 69 days. There were three patients who suffered from local skin erosion at the site of catheter entry, and seven who developed diarrhea and/or a feeling of abdominal fullness, but none of the patients showed any signs of peritonitis or ileus. The morbidity rates related to enteral nutrients and placement of the catheter jejunostomy were 8.9% and 3.8%, respectively. These findings demonstrate that a broad-based attachment of the jejunal wall to the peritoneum at the place of entry of the catheter is useful for preventing leakage or twisting of the jejunum, and for reducing the incidence and severity of the complications of catheter jejunostomy feeding.

Catheterization↗
PubMed1999

Intraoperative lavage for cytological examination in 1,297 patients with gastric carcinoma.

BACKGROUND: This study examined the clinical value of intraoperative peritoneal lavage for cytological examination in patients with gastric cancer. Peritoneal dissemination is the most frequent mode of recurrence for this tumor. METHODS: A retrospective of lavage findings, other factors, and outcome was performed in 1,297 patients with gastric cancer who underwent intraoperative peritoneal lavage. RESULTS: The 5-year survival rate of patients with positive lavage cytology was only 2%. Patients who underwent curative resection and had negative cytology had a significantly better 5-year survival rate (P < 0.001). Even among patients with macroscopic peritoneal dissemination, the survival rate was significantly better with negative cytology, which reflected fewer free cancer cells in the peritoneal cavity. Serum concentrations of carcinoembryonic antigen and carbohydrate antigen 19-9 were significantly higher in patients with positive cytology. Multivariate analyses indicated that intraoperative cytological findings was an independent prognostic factor for survival, and was the most important factor for predicting peritoneal recurrence. CONCLUSIONS: Intraoperative peritoneal lavage cytology is important in predicting survival and peritoneal recurrence in gastric cancer.

Biomarkers, Tumor↗
PubMed1999

Consumption of vitamin E in coronary circulation in patients with variant angina.

OBJECTIVES: The plasma status of vitamin E has been suggested to be linked to the activity of coronary artery spasm. This study was designed to determine whether vitamin E is actually consumed in the coronary circulation in patients with active variant angina having repetitive spasm-induced transient myocardial ischemia and reperfusion. METHODS: Blood samples were obtained simultaneously from the aortic root, coronary sinus and right atrium in 12 patients with variant angina due to spasm of the left coronary artery, nine patients with stable effort angina and nine control subjects. Plasma vitamin E (alpha- and gamma-tocopherol) concentrations were determined by use of high-performance liquid chromatography and plasma lipid peroxides were measured as thiobarbituric acid-reactive substances (TBARS). RESULTS: At baseline, both plasma alpha- (p < 0.01) and gamma- (p < 0.05) tocopherol levels were significantly lower in the coronary sinus (5.50 +/- 0.50 and 0.55 +/- 0.07 mg/l, mean +/- SEM) than in the aortic root (6.63 +/- 0.57 and 0.63 +/- 0.08 mg/l) and also in the right atrium (6.44 +/- 0.61 and 0.63 +/- 0.09 mg/l) in the variant angina group. The TBARS level was significantly (p < 0.05) higher in the coronary sinus than in the aortic in this group. In contrast, these levels were not significantly different between the samples from the coronary sinus and the aortic root or the right atrium in the control group and also in the stable effort angina group. The coronary sinus-aortic difference in plasma vitamin E levels in the variant angina group was not significantly altered after left coronary artery spasm induced by intracoronary injection of acetylcholine. Also, the plasma vitamin E levels in the aortic root, coronary sinus and right atrium all remained unchanged in the stable effort angina group after pacing-induced angina and in the control group after intracoronary administration of acetylcholine. CONCLUSIONS: Transcardiac reduction in plasma vitamin E concentrations concomitant with lipid peroxide formation was demonstrated in patients with active variant angina, suggesting actual consumption of this major endogenous antioxidant. Oxidative stress and vitamin E exhaustion may be involved in the pathogenesis of coronary artery spasm.

Acetylcholine↗
PubMed1999

Identification of multiple HIV-1 CTL epitopes presented by HLA-B*5101 molecules.

We attempted to identify and characterize HIV-1 CTL epitopes presented by HLA-B51 which is associated with a slow progression to AIDS. HLA-B*5101 stabilization assay showed that 33 out of 172 HIV-1 peptides carrying HLA-B*5101 anchor residues bound to HLA-B*5101. Seven peptides were suggested as HIV-1 CTL epitopes presented by HLA-B*5101 because the specific CTL was induced for these peptides in PBMC from three HIV-1 seropositive individuals carrying HLA-B51 by stimulation with HLA-B*5101 binding peptides. Analysis of these epitopes using the specific CTL clones confirmed that six of seven HIV-1 peptides are epitopes presented by HLA-B*5101. Three epitopes presented by HLA-B*5101 are highly conserved among the clade B strain, suggesting that the specific CTL for these epitopes might play an important role in recognition of HIV-1 infected cells. These epitopes will be useful to analyze CTL responses in HIV-1 infected individuals.

Antigen Presentation↗
PubMed1999

Local administration of activin promotes fracture healing in the rat fibula fracture model.

Osteogenic activities of activin, a member of the transforming growth factor (TGF)-beta superfamily, have been demonstrated in both in vitro and in vivo studies. The present study investigates the effects of topical application of activin on fracture healing using rat fibula fracture models. Activin (0.4-10 microg/day) was injected locally to the fracture once a day for 2 weeks. Activin promoted callus formation in a dose-dependent manner and both callus volume and callus weight were significantly increased with doses of 2-10 microg/day activin. Also, 3 weeks of activin treatment increased the mechanical strength of the healing bone in addition to the callus mass. Histological study 2 weeks after the fracture revealed that activin promoted endochondral bone formation. Immunohistochemical examination of the fractured tibia revealed that activin was localized to osteoblasts and chondrocytes in the region ossified both endochondrally and intramembranously. These findings suggest that activin expressed during fracture healing promotes the healing process through an autocrine/paracrine mode of action.

Activins↗
PubMed1999

Sentinel lymphadenectomy in breast cancer: identification of sentinel lymph node and detection of metastases.

Sentinel lymphadenectomy is a useful way of assessing axillary status and obviating axillary dissection in patients with node-negative breast cancer. However, controversies remain concerning the optimal method to identify the sentinel lymph node (SLN) and detect micrometastases in this lymph node. We reviewed the literature concerning sentinel lymphadenectomy in breast cancer and reached the following conclusions: (a) A combination of preoperative lymphoscintigraphy with intraoperative dye-guided and gamma probe-guided methods achieves a higher rate of identification of SLN than any of these techniques alone. (b) Immediate and reliable intraoperative assessment of sentinel node status is vital to the technique's success. However, the reliability of sentinel node diagnosis using frozen sections is questionable, because micrometastatic foci cannot always be identified. (c) Hematoxylin and eosin (H&E) staining and/or immunohistochemistry on permanent sections are useful for the detection of micrometastases in the sentinel node. Although a reverse transcriptase-polymerase chain reaction (RT-PCR) method is more sensitive than H&E staining and immunohistochemistry, it would not distinguish benign from malignant epithelial cells in the SLN. Therefore, further study is required before sentinel lymphadenectomy gains general acceptance for patients with primary breast cancer.

Axilla↗
PubMed1999

Staging efficacy of breast cancer with sentinel lymphadenectomy.

Seventy-two patients underwent dye-guided or dye- and gamma probe-guided sentinel lymphadenectomy (SLND) followed by complete axillary lymph node dissection (ALND). The results of imprint cytology, frozen sections, and permanent sections of the sentinel lymph node (SLN) were compared to each other and to the histologic findings in the nonsentinel nodes. The SLN was identified in 62 (88%) of 72 patients. Evaluation of the SLN on the permanent sections yielded a diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100%, although the reliability of SLN diagnosis using frozen sections or imprint cytology is limited. Therefore, it may be concluded that SLND with multiple sectioning and histopathologic examination of the SLNs can predict the presence or absence of axillary-node metastases in patients with breast cancer. However, further studies will be needed to investigate the value of SLND in respect to the long-term regional control and any possible detriment or benefit to survival, before it can replace routine ALND as the preferred staging operation for operable breast cancer.

Adult↗
PubMed1999

Role of anchor residues in peptide binding to three HLA-A26 molecules.

To investigate the role of anchor residues in HLA-A26 binding peptides, we analyzed the binding of various peptides to three HLA-A26 molecules using the HLA class I stabilization assay. Of twenty nonamer peptides carrying anchors at P2 and P9, 3, 6 and 3 peptides bound to HLA-A*2601, HLA-A*2602 and HLA-A*2603, respectively The peptide EV-IPMFSAL bound most strongly to these three HLA-A26 molecules. Analysis using mutants of this peptide at P1, P2 or P9 showed that acidic amino acids at P1 and five hydrophobic residues (Val, Thr, Ile, Leu and Phe) at P2 are anchor residues for the three HLA-A26 molecules while with exception of positively charged amino acids, a broad range of amino acids function as P9 anchor residues. These anchors were further evaluated using 38 nonamer peptides carrying anchor residues at P1, P2 and P9. Nineteen of these peptides bound to at least one HLA-A26 molecule. The frequency of HLA-A26 binding peptides was higher for peptides carrying all three anchor residues than for peptides carrying only P2 and P9 anchor residues. These results indicate that in addition to P2 and P9 anchors, the P1 anchor plays an important role in peptide binding to three HLA-A26 molecules.

Amino Acid Sequence↗
PubMed1999

Therapeutic effect of an anti-Fas ligand mAb on lethal graft-versus-host disease.

Several anti-Fas ligand (FasL) inhibitory mAb (FLIM) were raised and characterized in this study. One, FLIM58, showed more potent neutralizing activity than Fas-Fc, the previously established artificial neutralizing agent for FasL. Several murine models of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation have been used to show that both FasL and perforin, the major effector molecules of cytotoxic T lymphocytes, are involved in this disease. In our GVHD model, FasL rather than perforin was associated with lethality. Administration of FLIM58 or Fas-Fc reduced the weight loss and mortality caused by GVHD, although other signs of GVHD, such as skin lesions, lymphoid hypoplasia and mononuclear cell infiltration in the liver, did not improve significantly. FLIM58 was more effective than Fas-Fc in reducing mortality. Our results demonstrated that neutralizing agents for FasL are therapeutic for lethal GVHD.

Amino Acid Sequence↗
PubMed1999

Soy protein peptic hydrolysate with bound phospholipids decreases micellar solubility and cholesterol absorption in rats and caco-2 cells.

This experiment was designed to evaluate the effects of casein, soy protein, soy protein with bound phospholipids (SP), soy protein peptic hydrolysate (SPH) or soy protein peptic hydrolysate with bound phospholipids (SPHP) on the micellar solubility of cholesterol and the taurocholate binding capacity in vitro. We also evaluated the effects of various proteins on cholesterol metabolism in rats and Caco-2 cells. SPHP had a significantly greater bile acid-binding capacity than that of SPH in vitro. Micellar cholesterol solubility in vitro was significantly lower in the presence of SPHP compared to casein tryptic hydrolysate (CTH). The cholesterol micelles containing SPHP and SPH significantly suppressed cholesterol uptake by Caco-2 cells compared to the cholesterol micelles containing CTH. Consistent with these findings in the in vivo cholesterol absorption study using radioisotopes, fecal excretion of total steroids was significantly greater in rats fed the SPHP diet compared with those fed the casein, soy protein, SP and SPH diets. Serum total cholesterol was significantly lower in rats fed SPHP than in those fed casein. The concentrations of total lipids and cholesterol in liver were significantly lower in the SPHP-fed group compared with all other groups. These results suggest that the suppression of cholesterol absorption by direct interaction between cholesterol-mixed micelles and SPHP in the jejunal epithelia is part of the mechanism underlying the hypocholesterolemic action of SPHP. SPHP may also inhibit the reabsorption of bile acids in the ileum, thus lowering the serum cholesterol level.

Amino Acids↗
PubMed1999

Role of nodal involvement and the periductal soft-tissue margin in middle and distal bile duct cancer.

OBJECTIVE: To determine the pattern of middle (Bm) and distal (Bi) bile duct cancers in an attempt to optimize surgical treatment. SUMMARY BACKGROUND DATA: Lymph node involvement and neural plexus invasion are the prognostic factors most amenable to surgery in Bm and Bi disease. However, a detailed analysis of these factors has not been conducted. METHODS: Fifty patients with Bm and Bi disease (Bm 14 patients, Bi 36 patients) were examined histopathologically. A precise determination was made of lymph node involvement and neural plexus invasion. Important prognostic factors were examined by clinicopathologic study to apply these findings to surgical management. RESULTS: Frequencies of nodal involvement for Bm and Bi disease were 57% and 71%, respectively. The inferior periductal and superior pancreaticoduodenal lymph nodes were most commonly involved. Neural plexus invasion occurred in 20% of patients, particularly involving the plexus in the hepatoduodenal ligament and pancreatic head. Tumor was present at the surgical margin in 50% and 14% of patients with Bm and Bi disease, respectively. Five-year survival rates were 65% in the absence of nodal metastasis and 21% with nodal metastasis. A significant correlation existed between absence of tumor at the surgical margin and survival. A Cox proportional hazard model projected absence of tumor at the surgical margin, followed by nodal involvement, as the strongest prognostic variables. CONCLUSIONS: Absence of tumor at the surgical margin and nodal involvement are important independent prognostic factors in Bm and Bi disease. Skeletonization of the hepatoduodenal ligament, including portal vein resection, is necessary for patients with Bm disease, and a wide nodal dissection is essential in all patients.

Adult↗
PubMed1999

Absence of myocardial ischemia during sudden controlled occlusion of coronary arteries in patients with well-developed collateral vessels.

OBJECTIVE: To determine whether the presence of well-developed collateral vessels (visualized by baseline angiography) prevents myocardial ischemia associated with electrocardiographic ST-segment deviation or anginal pain during subsequent coronary balloon occlusion. METHODS: Study patients with stable effort angina but without complete coronary obstruction were divided into two groups on the basis of whether myocardial ischemia was observed during the first minute of coronary balloon occlusion in order to compare the degrees of collateral development at baseline. Patients in group A (n = 47) had electrocardiographic ischemic ST-segment deviations or angina, or both, during balloon inflation, whereas patients in group B (n = 13) had neither. RESULTS: The incidences both of poor anterograde perfusion with TIMI grade 1 or 2 (77 versus 38%, P < 0.05) and of well-developed collateral vessels (Rentrop grade 3) in the perfusion territory of the target vessel for coronary angioplasty (77 versus 15%, P < 0.01) were higher for patients in group B than they were for those in group A. The incidence of no myocardial ischemia during balloon inflation among the patients with well-developed collateral vessels was higher than that among those without (59 versus 7%, P < 0.01). The prediction of the absence of myocardial ischemia during balloon inflation according to whether well-developed collateral vessels were present had the sensitivity 77% (10 of 13) and the specificity 93% (40 of 43) for the study patients. CONCLUSION: Absence of myocardial ischemia (revealed by electrocardiographic changes or angina during transient coronary balloon occlusion) was associated with presence of well-developed collateral vessels (Rentrop grade 3; visualized by baseline angiography), suggesting that the patients with well-developed collateral vessels have a low risk of developing acute myocardial infarction or hemodynamic instability upon abrupt closure of the culprit coronary artery.

Angioplasty, Balloon, Coronary↗
PubMed1999

Expression of nerve growth factor in hepatolithiasis.

AIMS/BACKGROUND: Nerve growth factor (NGF) has recently been shown to influence the survival and function of non-neuronal inflammatory cells, possibly through its activity as a colony-stimulating factor. It may also play an important role in acute inflammation and tissue repair. However, no prior report has focused on NGF in chronic inflammatory diseases of the gastrointestinal and biliary tracts. The aim of this study was to examine the expression of NGF in hepatolithiasis. METHODS: Twenty-six liver specimens resected from 22 patients with intrahepatic calcium bilirubinate stones and from 4 patients with intrahepatic cholesterol stones were examined immunohistochemically. RESULTS: The 22 patients with calcium bilirubinate stones demonstrated NGF immunoreactivity associated with surrounding inflammatory cells that was localized to the epithelia of proliferative peribiliary glands in the ductal wall. However, neither the surface lining of the bile duct nor hepatocytes expressed detectable NGF immunoreactivity. In the cholesterol stones cases in contrast, peribiliary glandular elements and inflammatory cell infiltration were less extensive than those observed in cases of calcium bilirubinate stones, and NGF immunoreactivity was not noted. CONCLUSIONS: These observations suggest that proliferative peribiliary glands express NGF protein in chronic proliferative cholangitis. This is characteristic of intrahepatic calcium bilirubinate stones.

Adult↗