Biomedical subjects
T Yamamura
Publications and source records attributed to T Yamamura.
Anoabdominal rectal resection and colonic J pouch-anal anastomosis: 10 years' experience.
BACKGROUND: Coloanal anastomosis and radiotherapy for the treatment of lower rectal carcinoma have been receiving increasing attention. METHODS: Patients with rectal cancer were divided into two groups: anoabdominal rectal resection and colonic J pouch-anal anastomosis (CAA) plus preoperative intraluminal brachytherapy (IBT) (group 1; 68 patients) and CAA without IBT (group 2; 23 patients). Group 3, comprising 59 patients who underwent abdominoperineal excision (APE), was examined as a control group. Comparative results were reviewed. RESULTS: Postoperative complications occurred more frequently in group 1 than in group 2. Actuarial 5-year survival rates were 73 per cent in group 1, 64 per cent in group 2 and 63 per cent in group 3. Cumulative local recurrence rates at 5 years were 11 per cent in group 1, 38 per cent in group 2 and 21 per cent in group 3. Intestinal continuity breakdown was seen in 14 per cent of all patients at 5 years after initial operation. CONCLUSION: The combination of CAA and preoperative IBT resulted in decreased local recurrence. IBT followed by CAA can be a good restorative option for combating lower rectal cancer.
[Continuous hepatic arterial infusion of fluorouracil with leucovorin for liver metastases from colorectal cancer].
Sixteen patients with liver metastases from colorectal cancer were treated by continuous intraarterial chemotherapy of 5-FU and leucovorin. The regimen was that 500 mg/body of 5-FU with 30 mg/ body of leucovorin was administered continuously for 5 days followed by no medication for 16 days. The effect of this therapy was evaluated, and the relationship between this therapy and p53 overexpression was also studied. A complete response was obtained in 3 patients and a partial response in 3 patients; the overall response rate was 38%. The response rate was 56% in patients of more than 6 courses, 57% in patients with positive p53, and 20% in patients with negative p53. The three-year survival rate was 31%, and median survival was 18 months. Duodenal ulcer occurred in 2 patients due to extravascular dislocation of catheter. A high response rate and favorable prognosis were obtained by this therapy. Maintenance of catheter and a short administration period are current issues.
[A case of adenocarcinoma of the gallbladder with lymph node metastasis showing hepatoid adenocarcinoma and producing alfa-fetoprotein].
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Autoimmune response in chronic ongoing myocarditis demonstrated by heterotopic cardiac transplantation in mice.
BACKGROUND: Autoimmune mechanisms have been implicated in the pathogenesis of chronic ongoing myocarditis. To investigate this relation, we used an A/J mouse model inoculated with coxsackievirus B3 and determined whether myocarditis would be transferred to normal hearts that were heterotopically transplanted. METHODS AND RESULTS: Inbred 3-week-old A/J mice were inoculated intraperitoneally with coxsackievirus B3 (Nancy strain; 2 x 10(4) plaque-forming units) and housed for > 60 days. The presence of the viral genome in the myocardium was determined by the polymerase chain reaction with primers specific for the 5' end of the coxsackievirus B3 genome performed at 40, 50, or 60 days after inoculation. Normal A/J mouse hearts were transplanted into the same strain of mice without myocarditis (group A) and into mice with chronic ongoing myocarditis (group B). The hearts were evaluated histologically 2 weeks after transplantation. Conventional histological examination of infiltrated T cells and macrophages was performed, and the expression of intercellular adhesion molecule-1, major histocompatibility complex (MHC) class I antigen, and MHC class II antigen was evaluated by immunoenzymatic staining. The concentrations of interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor (TNF-alpha) in the grafts were measured with an ELISA. The viral RNA genomes were not detected in the mice with chronic ongoing myocarditis, but their transplanted hearts did show myocarditis. In the hearts with induced myocarditis, infiltrated mononuclear cells consisted of CD4+ T cells, CD8+ T cells (CD4+ cell number > CD8+ cell number), and macrophages. Intercellular adhesion molecule-1, MHC class I antigen, and MHC class II antigen were expressed in the vascular endothelial cells and myocardial cells in and around the infiltrated lesions. The concentrations of IL-1 alpha and TNF-alpha in group B were significantly higher than those in group A (group A versus group B: IL-1 alpha, 125 +/- 35 versus 180 +/- 34 pg/mL; TNF-alpha, 45 +/- 15 versus 96 +/- 40 pg/mL; P < .05). CONCLUSIONS: Results suggest that an autoimmune response may play a key role in the progression of chronic ongoing myocarditis.
An alpha-chain TCR CDR3 peptide can enhance EAE induced by myelin basic protein or proteolipid protein.
Regulation of experimental autoimmune encephalomyelitis (EAE) can be induced by anti-idiotype immunity against T cell receptor (TCR) fragments associated with major histocompatibility complex (MHC) molecules. However, we have recently found that preimmunization with an alpha-chain TCR CDR3 peptide (LYFCAARSNYQL) derived from myelin basic protein (MBP)-specific clones did not suppress but rather augmented the severity of EAE induced by MBP-specific T cells in SJL/J mice. To test whether CDR3 vaccination could control only a highly restricted T cell population, we studied the effect of the peptide against EAE induced by T cells specific for different Ag/MHC ligands and autoimmune diseases affecting non-neural tissues. In contrast to expectations, the peptide was found to augment not only EAE induced by MBP-specific T cells, but also proteolipid protein (PLP)-specific T cell- or PLP peptide-induced EAE in SJL/J mice, and MBP-induced EAE and adjuvant arthritis (AA) in rats. The CDR3 peptide was neither inhibitory nor supportive for Ag-induced activation of an encephalitogenic clone in vitro. In addition, the peptide treatment neither inhibited the induction of Ag-specific T cells nor altered the APC function of spleen cells. These findings, on the one hand, confirm previous results showing TCR peptide-induced enhancement of the disease and, on the other hand, indicate that the TCR CDR3 peptide may control T cells with broader Ag/MHC specificities than could be expected. Structural similarity among TCR idiotypes of autoimmune T cells may partly account for these results.
T-T cellular interaction between CD4-CD8- regulatory T cells and T cell clones presenting TCR peptide. Its implication for TCR vaccination against experimental autoimmune encephalomyelitis.
Regulatory T cells recognizing TCR determinants presumably play a critical role in the control of experimental autoimmune encephalomyelitis, a prototype tissue-specific autoimmune disease. This study was initiated to determine whether regulatory T cells can be induced against a V beta 17a CDR2 peptide (residues 50-68) in SJL/J mice. Although the TCR peptide showed regulatory effects in vivo, the presence of T cells specific for the peptide could not be proven with conventional proliferation assays. Unexpectedly, in the presence of myelin basic protein-specific T clone cells (Tcc), the sensitized spleen cells vigorously proliferated in response to the TCR peptide. The subsequent experiment showed that this was due to the outstanding capability of the Tcc as APC for the exogenous TCR peptide. Using the Tcc as APC, we were able to establish V beta 17a50-68-specific T cell lines from in vivo primed spleen cells. The line cells were MHC class I restricted and dominated by T cells with a distinct surface phenotype (CD4-CD8-V beta 17a+). Presentation of the peptide by the Tcc was inhibited by treatment with gelonin that could block a MHC class I presentation pathway. The ability of T cells to present the TCR peptide was not related to their Ag specificity, but correlated with the expression levels of MHC class I molecules and adhesion molecules such as intercellular adhesion molecule-1 and B7-1 on their surface. The TCR peptide-specific T cells produced a soluble mediator(s) that is inhibitory for T cell activation and were protective against actively induced experimental autoimmune encephalomyelitis. These results show that V beta 17a50-68 vaccination induces regulatory CD4-CD8- T cells that could interact with T cells presenting relevant TCR fragments.
Human CAAF1 gene--molecular cloning, gene structure, and chromosome mapping.
We have isolated and characterized a cDNA and the gene of the human homologue of CAAF1, a novel member of the S100 calcium-binding protein family. The 276-bp open reading frame encoded a 92-amino acid polypeptide with a predicted molecular mass of 10,575 Da. The deduced amino acid sequence of human CAAF1 showed 66% homology to bovine CAAF1. The human CAAF1 gene consisted of three exons, with the two EF hand motifs of the CAAF1 protein separately encoded by exons 2 and 3. This gene was expressed at a high level in polymorphonuclear leukocytes and at an intermediate level in esophageal mucosa. The tissue distribution of CAAF1 mRNA was different from that of other S100 proteins. Direct R-banding fluorescence in situ hybridization revealed that the human CAAF1 gene was mapped to chromosome 1q21.2-q22, where most of the S100 genes form a cluster.
Use of transrectal ultrasonography to select type of surgery for villous tumors in the lower two thirds of the rectum.
OBJECTIVE: To determine the accuracy of transrectal ultrasonographic (TRUS) staging of rectal villous tumors when used to select a surgical procedure. DESIGN: Case series. SETTING: College hospital, Hyogo, Japan. PATIENTS: From 1988 to 1995, 24 patients were treated for villous tumors after diagnosis by TRUS, and were followed up for 0.5 to 7.5 years. MAIN OUTCOME MEASURES: Ultrasonographic tumor stage (u-T), pathologic tumor stage (p-T), biopsy findings, and surgical procedures were studied. RESULTS: Overall, 71% of the tumors were accurately staged by TRUS. However, 4 u-T1 and 3 u-T2 tumors were overstaged, with pathological examination showing 2 adenomas and 5 p-Tis tumors. Three of these 7 patients were overtreated surgically. The results of a biopsy predicted adenoma in 2 of the u-T1 tumors and 2 of the u-T2 tumors that were overstaged by TRUS. Pathological examination revealed that an enlarged lymphoid follicle in the mucosa had deformed the thin muscle layer of the rectal wall and abolished its continuity on TRUS imaging. The weakness of TRUS would seem to be in the accuracy of p-Tis staging. CONCLUSIONS: Transrectal ultrasonography had the advantage of predicting malignant infiltration in rectal villous tumors. The surgeon should know the limitations of TRUS diagnosis to select the most appropriate operation for each patient.
Defecographic assessment after colonic J pouch-anal anastomosis.
Colonic J pouch anal anastomosis is widely employed after rectal resection. In the 36 patients who participated in our retrospective study, although postoperative continence was retained/maintained in each individual, a survey questionnaire indicated some difficulties in neoanorectal function. Therefore, defecography was performed in 20 of these patients. Patients experiencing soiling were found to have an increased ano-pouch angle and pelvic floor descent. Loss of sensation and incomplete evacuation were also associated with an abnormally large pelvic floor descent. However, stool frequency, urgency, and the need for medication showed no correlation with any of the defecography parameters. These findings thus suggested that the puborectal muscle and the levator ani muscle played an important role in postoperative function. Defecography was also found to provide a dynamic assessment of the postoperative state of colonanal reconstruction.
Modification of the stapled functional end-to-end anastomosis for ileostomy closure.
The use of stapling devices simplifies ileostomy closure; however, the original functional end-to-end anastomotic technique creates intersecting staple lines, generally causing disruption of the anastomosis at the intersections. Therefore, we modified the stapling technique to prevent the two staple lines from crossing. After the everted ileostomy spout is turned back, a stapled side-to-side anastomosis is made. Everting traction sutures are then placed around the ileostomy orifice prior to closure with a linear stapler, thus ensuring that this staple line does not cross the V-shaped staple line of the intestinal anastomosis. This modified technique was employed in the treatment of 20 patients, none of whom developed any signs of anastomotic leakage or intestinal obstruction.
Preoperative detection of distal intramural spread of lower rectal carcinoma using transrectal ultrasonography.
PURPOSE: Usefulness of transrectal ultrasonography (TRUS) for detecting distal intramural spread of rectal carcinoma was investigated. METHODS: Thirty-seven patients with advanced rectal carcinoma, who had not received preoperative adjuvant therapy, underwent TRUS before surgery. Distal intramural spread was evaluated by TRUS and by pathologic examination of resected specimens. RESULTS: Distal intramural spread was found in 7 of 37 patients (19 percent) by pathologic examination. Presence or absence of distal intramural spread was correctly diagnosed by TRUS in 86 percent of the 37 patients. Misdiagnosis by TRUS mainly occurred when distal intramural spread was 5 mm. Tumor penetration of muscularis propria, lymph node involvement, and a higher histologic grade of malignancy showed a significant relationship with the presence of distal intramural spread. CONCLUSION: TRUS was useful for detecting distal intramural spread > 5 mm in patients with lower rectal carcinoma and may be helpful for selecting appropriate surgery.
Nerve growth factor induces resistance of PC12 cells to nitric oxide cytotoxicity.
Nitric oxide (NO) donors, sodium nitroprusside and NOC 7, caused pheochromocytoma (PC12) cell death in a concentration and time-dependent manner. This cytotoxicity was blocked by the NO trapping agent, oxyhemoglobin. A membrane permeable cGMP analogue had no cytotoxicity in a reasonable concentration. Moreover, the selective inhibitor of cGMP-dependent protein kinase, KT5823, had no effect on NOC 7 cytotoxicity. These results suggest that NO caused PC12 cell death but not through the cGMP pathway. Additionally, this NO-induced PC12 cell death is not accompanied by DNA fragmentation. Nerve growth factor (NGF), which is able to rescue PC12 cells from serum deprivation, failed to protect PC12 cells from NO-induced cell death by acute treatment. However, PC12 cells differentiated by NGF treatment for more than 3 days did not die after NO exposure. The differentiated PC12 cells, but not undifferentiated cells, expressed NO synthase (NOS). NGF-differentiated PC12 cells acquired the resistance to NO, by a mechanism not yet identified, accompanied by the expression of NOS.
TCR repertoire to proteolipid protein (PLP) in multiple sclerosis (MS): homologies between PLP-specific T cells and MS-associated T cells in TCR junctional sequences.
In the pathogenesis of multiple sclerosis (MS), autoimmune T cells reactive with proteolipid protein (PLP) may play a crucial role. We determined 23 TCR beta-chain sequences of limiting dilution T cel lines (TCL) selected against a synthetic peptide, PLP 95-116, 105-124 or 139-155, from the peripheral blood of three Japanese MS patients with the DR2,w15 haplotype (TI, SK and OK). Fourteen sequences were originated from TI, seven from SK and two from OK. The PLP-reactive TCL utilized various Vbeta and Jbeta gene segments, but there was significant bias in the Vbeta and Jbeta usage. Overutilization of the Vbeta2 family and dominant usage of the Jbeta2.5 subfamily was seen in PLP 105-124-reactive and 95-116-reactive TCL respectively. More remarkably, a majority of the TCL were found to express beta-chain CDR3 motifs that appear to be unique to MS brain infiltrates. In contrast, these motifs were only rarely seen in control TCR sequences from peripheral blood or from a TCL selected against tetanus toxoid. In several cases, the betaCDR3 homologies between the PLP-reactive T cells and MS brain T cells were extensive, owing to the shared motifs in combination with the surrounding amino acid identities. These results indicate that PLP-specific T cells may be involved in the immunopathology of MS.
A pathogenic mechanism of chronic ongoing myocarditis.
To clarify the pathogenetic mechanism of chronic ongoing myocarditis, we produced Coxsackievirus B3-induced myocarditis in A/J mice and immunopathologically examined the microcirculation in the chronic phase of myocarditis. Forty-two 3-week-old A/J mice were inoculated intraperitoneally with Coxsackievirus B3 (Nancy strain) 2 x 10(4) PFU (plaque-forming units) and sacrificed 7, 14, 21, 50, 90, or 120 days later. To evaluate myocardial microcirculation, 18 of the hearts were perfused from the thoracic aorta with warm 2% gelatin/carbon solution. The remaining hearts were quickly frozen for immunologic analysis with an enzyme immunostaining assay using monoclonal antibodies against CD4, CD8, macrophages, intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex class I or II. The presence of viral RNA genome in the myocardium at 40, 50, or 60 days after inoculation was evaluated using the polymerase chain reaction. The lesions in chronic ongoing myocarditis consisted of myocardial damage, myocardial calcification, interstitial fibrosis, and infiltration of mononuclear cells. These infiltrated lymphocytes were predominantly CD4+ T cells. Furthermore, microvascular abnormalities, including dilatation, tortuosity, constriction, and abrupt termination, were observed around the lesions. There was marked infiltration by mononuclear cells around the microvessels. ICAM-1 was strongly expressed in the endothelial cells of the vessels. Coxsackie B3 viral genome was not detected in the myocardium of mice with chronic ongoing myocarditis in each stage examined. These results suggest that an autoimmune mechanism is involved in the persistent inflammation seen in chronic ongoing myocarditis.
[Techniques for measurement of nitric oxide in biological systems: principles and practice].
Despite being small and simple in structure the nitric oxide free radical (NO.) is now proving to be of vital physiological significance, and it has been shown to play important roles in complex processes such as vasodilatation, inflammation, thrombosis, immunity and neurotransmission. To conduct meaningful research into the role of NO., it is necessary to accurately determine its concentration. Its direct and quantitative measurement, however, has been little discussed inspite of the abundance of studies on this compound. Generally most authors refer to indirect qualitative measurements, such as employment of NO-synthase inhibitors, measurement of cGMP or citrulline, and the detection of NO.-induced physiological effects such as vascular relaxation. The primary difficulties in the direct measurement of NO stem from its short lifetime and very low concentrations. Notwithstanding these problems, several quantitative methods for measuring NO. have been established. The most commonly used techniques are as follows: 1) UV-visible spectrophotometry of the diazotization product of the nitrite, NO-hemoglobin or methemoglobin, 2) fluorometry of the fluorescent product of the nitrite, 3) detection of chemiluminescence by its reaction with ozone or luminol/H2O2, 4) amperometric microelectrode assay, and 5) electron spin resonance spectrometry. All the aforementioned techniques have certain limitations that should be considered carefully prior to each application.
[Effects of halothane, isoflurane, enflurane, and sevoflurane on the monosynaptic reflex response in the isolated spinal cord of newborn rats].
Monosynaptic reflex responses (MSRs) in the isolated spinal cord of newborn rats were elicited in the ventral root by stimulation of the ipsilateral dorsal root. MSRs were considered to be mediated by non-NMDA class glutamate receptors. We studied the depressant effects of halothane, isoflurane, enflurane, and sevoflurane on MSR amplitudes as a function of anesthetic concentration comparing with MAC value of each anesthetics. The spinal cord of newborn rats were rapidly dissected out, and placed in a chamber superfused with artificial cerebrospinal fluid (ACSF, pH 7.4, 34 degrees C) equilibrated with 95% O2 - 5% CO2. Anesthetic gases were delivered with specific vaporizers and bubbled in the ACSF. Each anesthetic concentration was determined by gas chromatography. Either of the anesthetics reversibly depressed MSR amplitudes in a concentration dependent fashion. Concentration-response curves for MSR amplitudes were constructed and the concentrations which produced a half-maximum inhibition (IC50) were 0.56, 0.65, 0.97 and 1.18 mM for halothane, isoflurane, enflurane, and sevoflurane, respectively. These IC50 values correlated well with those of MAC values (r = 0.999, P < 0.001) obtained from adult rats in an in vivo condition. The MSR response in the isolated spinal cord of newborn rats is considered as a useful model for analysis of potency of volatile anesthetics.
[The effect of intraportal chemotherapy in terms of administered dose of 5-FU].
Forty-six patients with colorectal cancer were studied for the effects of intraportal chemotherapy in terms of the administered dose of 5-FU. No liver metastases occurred in patients with a total dose of more than 4 g of 5-FU. The five-year survival rate for patients with a total dose of more than 4 g of 5-FU was 98%, which was better than that for control (72%). In patients administered 500 approximately 600 mg/body/day of 5-FU, the concentration of 5-FU in the peripheral blood was 0.022 approximately 0.027 microgram/ml. Liver dysfunction occurred in 22%, 33%, and 80% of patients administered less than 4 g, 4 approximately 4.9 g, or more than 5 g of 5-FU, respectively, but almost all of them were grade 1. These results suggest that intraportal chemotherapy administered with a total of more than 4 g of 5-FU was effective for prevention of liver metastases after resection of colorectal cancer.