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Biomedical subjects

T Yamamura

Publications and source records attributed to T Yamamura.

At least 73 records · Page 4Linked to original sources

Clinicopathological variables and p53 overexpression as a combined prognosticator for hematogenic recurrence in colorectal cancer.

BACKGROUND AND OBJECTIVE: Precise evaluation of the prognostic factors for hematogenic recurrence after resection for colorectal cancer is important not only for the prediction of patient outcome but also for the determination of adjuvant therapy. The purpose of the current study was to elucidate the clinical significance of using clinicopathological variables in combination with p53 expression as a prognosticator for hematogenic recurrence. METHODS: One hundred forty-two patients with colorectal cancer were examined. The expression of p53 was determined by immunohistochemical staining. RESULTS: Eighteen (60%) of the 30 patients who were positive for both p53 overexpression and lymph node metastasis, 13 (41%) of the 32 patients who were positive for p53 and venous invasion, and 13 (39%) of the 33 patients who were positive for p53 and carcinoembryonic antigen (CEA) developed hematogenic recurrence. CONCLUSIONS: The combination of p53 overexpression and lymph node metastasis was an excellent prognostic indicator for hematogenic recurrence in colorectal cancer.

Adult↗

Current trends in restorative proctocolectomy: introduction of an ultrasonically activated scalpel.

PURPOSE: We evaluated the usefulness of an ultrasonically activated scalpel (Harmonic Scalpel) for mucosal proctocolectomy and ileal J-pouch-anal anastomosis. METHODS: Seventy-four patients with ulcerative colitis (70 patients) and familial adenomatous polyposis (4 patients) underwent mucosectomy using the Harmonic Scalpel since 1997. We compared the clinical and functional results with those of the monopolar electrocoagulator (forceps coagulation technique, 86 patients with colitis and 7 with polyposis). RESULTS: We performed graduated mucosal proctectomy by using the Harmonic Scalpel. The operative time (Harmonic Scalpel, 42 minutes vs. forceps coagulation technique, 85 minutes) and blood loss (Harmonic Scalpel, 33 ml vs. forceps coagulation technique, 86.8 ml) were significantly reduced by this method. The Harmonic Scalpel enabled restorative proctocolectomy by the synchronous approach within three hours. The functional results and complications were not significantly different between the two groups. CONCLUSION: The Harmonic Scalpel shortened the operative time, decreased blood loss, and was useful for restorative proctocolectomy in our study.

Adult↗

Transanal mucosectomy using an ultrasonically activated scalpel for ulcerative colitis.

We describe herein our technique of using an ultrasonically activated scalpel (Harmonic Scalpel [HS]) to simplify the procedure of anorectal mucosectomy for ulcerative colitis (UC). This technique was successfully employed to perform restorative proctocolectomy and ileoanal anastomosis (IAA) in ten patients with UC. By using the HS, thermal injury of the internal anal sphincter was avoided during mucosectomy, and we were able to dissect the inflamed mucosa sharply without causing bleeding. HS reduced the operative time and blood loss compared with the traditional forceps-coagulation technique. These results indicate that the introduction of this new scalpel will facilitate an increase in the number of cases of mucosectomy for IAA.

Adolescent↗

Posttraumatic intra-gallbladder hemorrhage in a patient with liver cirrhosis.

We report a case of intra-gallbladder hemorrhage secondary to blunt abdominal trauma in a patient with liver cirrhosis. A 58-year-old man was admitted to a local hospital with persistent right upper quadrant abdominal pain. Anemia was detected, and computed tomography (CT) revealed a high-density mass in the gallbladder lumen. He was transferred to our hospital because a gallbladder tumor was suspected. He had a history of habitual alcohol abuse and had sustained blunt abdominal trauma in the right upper quadrant 29 days before admission to our hospital (4 days before to the admission local hospital). The intra-gallbladder high-density mass depicted on the CT scan, observed as non-shadowing low-level echoes, was deemed to represent a blood clot on ultrasonography (US) performed 31 days after the trauma. US-guided percutaneous transhepatic gallbladder aspiration and cholecystography confirmed the presence of an old blood clot in the lumen. Because of the patient's persistent pain, a cholecystectomy was performed. The distended gallbladder was filled with old clotted blood.

Cholecystography↗

Characteristic cardiovascular manifestation in homozygous and heterozygous familial hypercholesterolemia.

BACKGROUND: The aortic valve dysfunction of patients with homozygous familial hypercholesterolemia (FH) suggests that hypercholesterolemia affects not only coronary arteries but also the aortic valve. We studied the aortic root of patients with homozygous FH and those of patients with heterozygous FH to characterize the premature atherosclerotic lesions by using histopathologic specimens. METHODS AND RESULTS: The aortic roots of 10 patients with homozygous FH, age 9 to 58 years, were studied by cardiac catheterization with several angiographies. The aortic roots of 39 patients with heterozygous FH under age 60 years were also examined for aortic and mitral valvular functions by color Doppler echocardiography, and 30 normocholesterolemic patients with coronary artery disease were examined as control subjects. In addition, in 22 patients with FH and 20 control subjects, the internal diameter of the aortic annulus and the aortic ridge in cardiac cycles were measured. Of the 10 homozygotes with FH, 8 patients had aortic regurgitation demonstrated by aortography; 3 of them showed significant transvalvular pressure gradients. Stenotic changes of coronary ostia were observed in 8 of the 10 homozygotes with moderate coronary atherosclerosis. Of the 39 heterozygotes with FH, 10 patients had aortic regurgitation shown by Doppler echocardiography, as did only 1 of the 30 control subjects (P <.05). The average diameter and distensibility of the ascending aorta were significantly reduced in the heterozygotes compared with the control subjects. The surgically resected cusp specimens of aortic valves obtained from 1 homozygous and 1 heterozygous patient showed significant thickening of the cusp with foam cell infiltration. CONCLUSIONS: Premature atherosclerosis in FH had a characteristic distribution, affecting the aortic root dominantly. The involvement of the aortic valve indicating "hypercholesterolemic valvulopathy" was a peculiar feature of FH, especially its homozygous form, but was reminiscent of ubiquitous processes caused by hypercholesterolemia.

Adolescent↗

Autonomic regulation of experimental autoimmune encephalomyelitis in IL-4 knockout mice.

The effect of chemical sympathectomy induced with 6-hydroxydopamine (OHDA) on experimental autoimmune encephalomyelitis (EAE) was studied in wild type and IL-4-/- C57BL/6 (B6) mice. When actively sensitized with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide, control B6 mice developed a mild form of EAE with full recovery. The sympathectomized mice developed paralysis with higher maximum disease score and did not recover completely, indicating that the sympathetic nervous system (SNS) down-modulates the process of EAE. Unexpectedly, however, sympathectomy resulted in suppression of EAE in IL-4-/- mice, implying that control of actively induced EAE by the SNS depends on the genetic background of mice. We also induced EAE by passive transfer of MOG35-55-reactive lymph node cells, and this disease was augmented by sympathectomy in both wild type and knockout animals. Further experiments showed that changes in T cell populations and the activity of antigen presenting cells might be responsible for the altered immune response and clinical course after sympathetic ablation. Our studies indicate that the absence of a single cytokine can severely alter nervous-immune system interactions.

Animals↗

Estradiol enhances the production of mineralized nodules by human periodontal ligament cells.

A primary objective in the treatment of periodontal disease is the regeneration of the mineralized and soft connective tissue. PDL cells produce mineralized nodules in vitro which is one of the important functions of PDL cells for regenerative therapy. The purpose of this study was to investigate the effects of estradiol on mineralized nodule formation by human PDL cells. PDL cells were obtained from healthy donors and maintained in DMEM with 10% fetal bovine serum. Serum-free medium was used when the effects of estradiol were tested. ALP activity in the supernatant of cells disrupted by sonication was analyzed spectrophotometrically. The formation of mineralized nodules was assessed by staining the PDL cells with alizarine red and counting the number of nodules. at Estradiol 20 ng/ml significantly enhanced the ALP activity and mineralized nodule formation compared to the control. These results suggested that estrogen status may modify the regenerative activity of periodontal tissue.

Adolescent↗

Selective activation of excitation-contraction coupling pathways by ET(A) and ET(B) receptors in guinea-pig tracheal smooth muscle.

1. Signalling events responsible for endothelin(A) (ET(A)) and ET(B) receptor-induced contraction were examined in epithelium-denuded guinea-pig tracheal smooth muscle strips. Selective stimulation of each subtype was achieved by a combination of ET-1 (100 nM) and ET(A) and ET(B) receptor-selective antagonists, BQ-123 (10 microM) and BQ-788 (3 microM), respectively. 2. Both ET(A) and ET(B) receptors induced long-lasting contraction that was totally dependent on Ca2+ influx. Stimulation of ET(A) receptor induced both transient and sustained (Ca2+)i increases whereas that of ET(B) receptor induced only a sustained increase. Suppression of the transient (Ca2+)i increase by U73122 (3 microM) did not affect the ET(A)-induced sustained (Ca2+)i increase and tension development. Stimulation of ET(A) receptor, but not ET(B), induced phosphoinositide breakdown and protein kinase C (PKC). The activated PKC contributed to the contraction by increasing the Ca2+ sensitivity of the contractile apparatus. 3. Thus, ET(A) receptor is coupled both with phospholipase C/Ca2+/PKC signalling and Ca2+ influx pathways whereas ET(B) receptor was coupled only with the latter. 4. Stimulation of ET(B) receptor, but not ET(A), caused membrane depolarization measured with a fluorescent indicator, bis-(1,3 dibutylbarbituric acid)-trimethine oxonol. Both nifedipine (1 microM) and verapamil (10 microM) abolished ET(B)-induced Ca2+ influx and contraction, while they barely affected ET(A)-induced responses. 5. Therefore, the Ca2+ influx pathways activated by each subtype appeared to be completely different; ET(A) and ET(B) receptors opens voltage-independent Ca2+ channels and L-type voltage-dependent Ca2+ channels, respectively.

Animals↗

Induction of prophages of enterohemorrhagic Escherichia coli O157:H7 with norfloxacin.

Norfloxacin (NFLX) caused induction of prophages VT1 and VT2 of enterohemorrhagic Escherichia coli O157 at subinhibitory concentrations. In time course experiments, we observed the following sequential events: upon induction, the phage genomes underwent multiplication; the amount of stx genes increased; and subsequently, large quantities of toxins VT1 and VT2 were produced. Further studies showed that the molecular mechanism of prophage induction is closely related to the RecA system since the prophage VT2 was not induced with NFLX in a recA mutant strain.

Coliphages↗

Fas expression and apoptosis correlate with cardiac dysfunction in patients with dilated cardiomyopathy.

Fas is a transmembranous glycoprotein that mediates apoptosis. To elucidate the roles of Fas and of myocyte apoptosis in patients with dilated cardiomyopathy (DCM), the expression of Fas and the fragmentation of DNA were compared in endomyocardial biopsy specimens obtained from patients with DCM. Endomyocardial biopsy was performed on 19 subjects (16 with DCM and 3 control subjects) who also underwent cardiac catheterization and echocardiography. Fas and bcl-2 expression were assayed immunohistochemically, and in situ TdT staining was performed to estimate the number of apoptotic cells. Samples from the DCM patients stained more intensely with anti-Fas antibody than those from control patients (p<0.05). The percentage of in situ TdT-positive cells was significantly higher in the DCM group than in the control group (p<0.05). A correlation between Fas expression and in situ TdT staining was observed in 67% of myocytes in the DCM group. Moreover, the percentage of in situ TdT staining was significantly higher in subjects with severely impaired left ventricular systolic function than in those whose systolic function was mild to moderately impaired, or who had normal systolic function (p<0.05). The samples showed little expression of bcl-2. These results suggest that Fas expression and apoptosis may be involved in the progression of cardiac dysfunction in DCM.

Adult↗

Repetitive coxsackievirus infection induces cardiac dilatation in post-myocarditic mice.

The relation between mycarditis and dilated cardiomyopathy (DCM) is controversial. To clarify the pathogenic mechanism of these diseases, the present study examined the effect of repetitive inoculation with coxsackievirus B3 (CVB3) in post-myocarditic mice. Inbred 3-week-old A/J mice were inoculated intraperitoneally with CVB3 (Nancy strain; 2x10(4) plaque-forming units) and reinfected in the same manner with CVB3 at 40 weeks (3W+/40W+). All mice were killed at 42 weeks old. The weight of the hearts of the 3W+/40W+ group were significantly increased compared with those of the 3W-/40W+ group, and both the heart weight/body weight and lung weight/body weight ratios of the 3W+/40W+ group were also significantly increased over those of the 3W-/40W- group, although the levels of serum neutralizing antibody titers were significantly increased in the 3W+/40W+ group over the level of the other groups. No increase in inflammatory cell infiltration or fibrosis progression was observed in the 3W+/40W+ group relative to the 3W+/40W- group, but the second inoculation resulted in a significant left ventricular dilatation and in left and right ventricular free wall thinning (3.31+/-0.20 mm vs 2.61+/-0.19 mm, p<0.05; 0.54+/-0.09 mm vs 0.72+/-0.16 mm, p<0.05, respectively). The sarcomere length was also significantly increased in the 3W+/40W+ group compared with that of the other groups, as determined by electron microscopy. Degenerative or necrotic areas in the infected hearts were not stained with anti-mouse IgG antibody, but were stained, only in 3W+/40W+ mice, with anti-mouse IgM antibody. The concentrations of TNF-alpha in the hearts of the 3W+/40W+ group were increased significantly over those of the 3W+/40W- group. Repetitive CVB3 infection produced cardiac dilatation without inflammatory cell infiltration in post- myocarditic mice. Autoimmunity mediated by the circulation of certain antibodies (eg, antibodies against the CVB3 genome or a CVB3-related protein) may be part of the pathogenic mechanism for this phenomenon. Thus, repetitive virus infection might contribute to the pathogenesis of cardiac dilatation.

Animals↗

[Infection and multiple sclerosis].

Multiple sclerosis is a putative autoimmune disease in which limited numbers of autoimmune T cells reactive to myelin basic protein or proteolipid protein would play critical roles in initiation or augmentation of the inflammatory processes. Owing to the recent immunological studies, it is now possible to discuss the possible link between infectious agents and the development of MS on the molecular terms. This article deals with key issues in this subject such as molecular mimicry between autoantigen and viral peptide, autoimmune T cell stimulation by bacterial superantigens, and regulatory network in MS. In addition to reviewing the current activity in other laboratories, I point out that there might be much more broader range of peptide ligands for autodestructive T cells causing MS. This postulate is based on our recent discovery for the presence of degenerate autoimmune T cells in animal model of MS (EAE). I also indicate the possibility that immune regulatory system could be destroyed by some infectious agents. These informations should have significant implications for management of MS patients.

Autoimmunity↗

Age- and sex-related differences of plasma activated factor VII levels in children.

Although the majority of factor VII (FVII) circulates in the zymogen form, low levels of activated factor VII (FVIIa) exist in plasma and play an important role in the initiation of tissue factor-induced coagulation. It has been reported that the concentrations of hemostatic components in children and adults are different. Here, we investigated the age- and sex-related differences of FVIIa and FVII antigen (FVIIag) levels in children at age of 10 (n = 123; males: n = 62; females: n = 61), and 13 (n = 105; males: n = 47: females: n = 58), and compared these levels with those of young adults (mean +/- SD of age: 29.6+/-6.0 years). In males, there was not a significant difference between the FVIIIa levels of 10-year-old children and 13-year-old children, but the FVIIa levels in adult controls were significantly higher than those in children. In females, the FVIIa levels in 13-year-old children were significantly higher than that in 10-year-old children, but there was not a significant difference between 13-year-old children and adults. Thus, our study showed that plasma FVIIa levels were lower in children than in adults, and the increase of FVIIa level was earlier in females than in males.

Adolescent↗

[Is portal infusion chemotherapy uneffective for hepatic recurrence after resection for colorectal cancer?].

Sixty-six patients with colorectal cancer were studied regarding effects of prevention of hepatic recurrence in completely performed portal infusion chemotherapy. The regimen was continuous administration of 500-875 mg/body of 5-FU for 7 days and intraportal administration of 10 mg of MMC before and after 5-FU administration. Hepatic recurrence rate was 7.6% and the five year survival rate was 83.3% in portal infusion group, and 16% and 71.3% in the control group; the difference was not significant. However, the hepatic recurrence rate in patients administered more than 4 g of 5-FU was 2.5%; there was a significant difference between the portal group and control group. The five-year survival rate for patients administered more than 4 g of 5-FU was 92.3%, which was significantly higher than at less than 4 g. Excellent effects for prevention of hepatic recurrence and prognosis were obtained in patients administered more than 4 g of 5-FU. Thus, the compliance of 5-FU in portal infusion chemotherapy is important. Also, administration of MMC is suspected to enhance the effect of portal infusion chemotherapy.

Adult↗

[Diagnosis of ulcerative colitis and the biopsy method].

The biopsy specimen should be oriented flat on a ground glass slide or on a piece of filter paper so that the submucosa is on the slide and the mucosa uppermost to allow proper histopathological interpretation. It is important to perform the biopsy based on a full knowledge of features of inflammatory diseases of the large intestine. Biopsies should be taken from apparently normal and abnormal mucosa. It is necessary to observe the mucosa of the colon carefully for any mass lesions to find dysplasia or cancer complicating the ulcerative colitis. Any suspicious areas should be liberally biopsied. Biopsies should also be performed at random, because of possible existence of dysplasia or cancer which is not visible at endoscopy. This occurs especially in the rectum; biopsies can also be performed after inversion of the endoscope.

Biopsy↗

[PMC (pharmacokinetic modulating chemotherapy) for advanced gastric cancer].

We performed pharmacokinetic modulating chemotherapy (PMC) postoperatively in patients with advanced gastric cancer and examined its antitumor and the side effects. Nineteen patients with advanced gastric cancer (all were above Stage II) were treated: 10 had undergone total gastrectomy and 9 distal gastrectomy. UFT (400 mg/day) was orally administered daily and a continuous infusion of 5-FU (600 mg/m2/24 hr) was given once a week. The average observation period was 14.26 months (4-30 months). All patients with Stage II or III disease have survived, but two patients with Stage IV disease died. One patient received insufficient PMC and the other had a liver metastasis. Two patients experienced Grade 3 inappetence, but all other side effects were Grade 2 or lower and the incidence was less than 25%. In conclusion. PMC has tolerable side effects and may be effective in postoperative chemotherapy for advanced gastric cancer.

Administration, Oral↗

Molecular and clinical study of familial adenomatous polyposis for genetic testing and management.

Familial adenomatous polyposis (FAP) is an inherited predisposition to colorectal cancer characterized by the development of numerous adenomatous polyps, predominantly in the colorectal region. Germline mutations of the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis. We examined germline mutations of the APC gene and clinical features among eighty-seven individuals who consisted of thirty-nine FAP-patients, thirty-seven of their family members with a 1 in 2 risk of predisposition to this disease, and eleven normal persons. We accurately identified nine heterozygotes, among individuals with a 1 in 2 risk by genetic testing, without the uncertainty of the recurrence risk calculated by Bayes' theorem. Six of the nine heterozygotes were confirmed to have colorectal polyps by colonoscopic examination. Since they were diagnosed at 12.7 years-of-age on average, and were no more than 20 years old, they could be treated to prevent colorectal cancer. Based on the genotype-phenotype correlation, we concluded that the germline mutations responsible for the sparse polyps phenotype of FAP-patients tend to locate from codon 1055 in the proximal region of the APC gene, while those for the profuse type locate from codon 1102 in the distal region. Among the thirty-nine FAP-patients, we found that those with the germline mutations within codon 1055 and codon 1262 had colorectal carcinomas of an advanced stage, at a high rate (71.4%). Special attention and aggressive intervention is needed in these patients and relatives at risk. With reasonable and appropriate management, it should be possible to prolong and improve the quality of life of those family members both affected and at risk.

Adenomatous Polyposis Coli↗