Search PubMed⌕ Search

Biomedical subjects

N Tanaka

Publications and source records attributed to N Tanaka.

At least 181 records · Page 10Linked to original sources
PubMed2001

Novel murine autoimmune-mediated liver disease model induced by graft-versus-host reaction and concanavalin A.

BACKGROUND AND AIMS: We have previously reported that cluster of differentiation (CD)4+ T cells induced autoimmune liver diseases in mice with graft-versus-host reaction (GVHR) because of major histocompatibility complex (MHC) class II disparity. To analyze the progression of the autoimmune-related mechanism in the liver, concanavalin A (Con A) was injected in mice undergoing GVHR. The aim of this study is to clarify whether Con A deteriorates murine hepatic lesions induced by GVHR, and to elucidate the participation of the cytokines of liver-infiltrating CD4+ T cells. METHODS: Mice (F1; B6.C-H-2(bm12) x B6) were intravenously injected with B6 T spleen cells. Concanavalin A (15 mg/kg) was administrated 5 days after cell transfer. We examined serum transaminase, antimitochondrial antibodies (AMA), antinuclear antibodies (ANA) and histological changes. Liver-infiltrating CD4+ T cells were sorted and their cytokine mRNA expression was examined by the use of reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Graft-versus-host reaction + Con A mice revealed an elevated serum transaminase, elevated AMA and ANA titers, increased periportal cellular infiltration, piecemeal necrosis and bridging necrosis in the liver. In this group, interferon (IFN)-gamma mRNA expression was more elevated than it was in the GVHR mice. However, there was no difference in the expression of interleukin (IL)-10 mRNA between the two groups. CONCLUSION: The results suggest that Con A deteriorates the GVHR-induced hepatic lesions, and IFN-gamma and IL-10 of CD4+ T cells might be implicated in the progression of autoimmune-related hepatic lesions. This model might offer an aspect for the investigation of progressive mechanisms in T-cell- mediated hepatobiliary injury.

Analysis of Variance↗
PubMed2001

Severe hepatitis caused by Epstein-Barr virus without infection of hepatocytes.

Although hepatitis is a common feature of primary Epstein-Barr virus (EBV) infection, severe liver injury is rare and its pathogenesis is unclear. A previously healthy girl developed severe hepatitis with prolonged jaundice. Serologic examination showed that she had primary infection with EBV. An extremely high Epstein-Barr viral load was observed in her peripheral blood. The viral load decreased in parallel with symptomatic improvement. Histologic examinations showed spotty necrosis of the liver parenchyma and infiltration by CD8(+) T cells. The CD8(+) T cells, not hepatocytes, were positive for EBV. Possible mechanisms of viral hepatitis without infection of hepatocytes are discussed.

Antigens, Viral↗
PubMed2001

Etiologic significance of defects in cholesterol, phospholipid, and bile acid metabolism in the liver of patients with intrahepatic calculi.

Intrahepatic calculi, highly prevalent in the Far East, including Japan, are characterized clinically by chronic proliferative cholangitis with frequent stone recurrences. Intrahepatic calculi consist of 2 groups, i.e., brown pigment stones, including a high cholesterol content, and cholesterol stones, with the former predominating. To gain insights into the pathogenesis of intrahepatic calculi, cholesterol and bile acid biosynthesis, as well as alterations in intracellular transport and/or canalicular secretion of phospholipid and bile acid were investigated in liver of patients with intrahepatic calculi. Enzyme activities of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase were increased (12.8 +/- 1.9 pmol/min/mg protein, mean +/- SEM vs. 5.5 +/- 0.4 in controls; P < .01) and cholesterol 7 alpha-hydroxylase activities were decreased (1.3 +/- 0.4 vs. 4.9 +/- 0.6; P < .01) in liver specimens of patients with brown pigment stones. In addition, messenger RNA (mRNA) levels of multidrug resistance P-glycoprotein 3 (MDR3 Pgp) and phosphatidylcholine transfer protein (PCTP) were markedly low in the liver specimens compared with the levels in specimens of control subjects, gallbladder stone patients, and patients with obstructive cholestasis. The protein levels and the immunohistochemical staining were decreased for MDR3 Pgp and PCTP in the liver. Consistently, the concentrations of phospholipid were markedly reduced in the hepatic bile from both affected and unaffected hepatic segments. In patients with intrahepatic calculi, biliary cholesterol supersaturation and the formation of cholesterol-rich brown pigment as well as cholesterol stones may be attributed to decreased hepatic transport and biliary secretion of phospholipids, in the setting of increased cholesterogenesis and decreased bile acid synthesis.

Adult↗
PubMed2001

Secondary sclerosing cholangitis and portal hypertension after O157 enterocolitis: Extremely rare complications of hemolytic uremic syndrome.

The authors experienced an extremely rare case of secondary sclerosing cholangitis and portal hypertension developed as late complications of hemolytic uremic syndrome (HUS) owing to Escherichia coli O157:H7 in a 2-year-old boy. HUS after E coli O157 infection is the most frequent cause of acute renal failure in childhood and occasionally is accompanied by extrarenal complications such as encephalopathy, cardiomyopathy, ischemic colitis, and pancreatitis. Rarely, late colonic stenosis may develop secondary to the ischemic damage. Sclerosing cholangitis and subsequent cirrhosis with portal hypertension are very uncommon as late complications of HUS. To our knowledge, such a case has not been previously reported in the literature. J Pediatr Surg 36:1838-1840.

Child, Preschool↗
PubMed2001

The efficacy of intra-articular analgesia after total knee arthroplasty in patients with rheumatoid arthritis and in patients with osteoarthritis.

The pain relief provided by intra-articular injection of morphine plus bupivacaine after total knee arthroplasty (TKA) plus partial synovectomy in patients with rheumatoid arthritis was compared with pain relief after TKA alone in patients with osteoarthritis. There were lower pain scores, a much smaller requirement for systemic analgesics, longer duration until the first requirement of systemic analgesics, and improvement in the range of motion of the knee joint in the patients who received intra-articular injection of analgesics. There was more pronounced postoperative analgesia in the patients with rheumatoid arthritis than in the patients with osteoarthritis in the study groups that received intra-articular injection of analgesics.

Analgesia↗
PubMed2001

The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients.

To investigate, by a multi-institutional randomized trial, the prognostic significance of the augmentation of tumour-infiltrating lymphocytes (TILs) by preoperative intratumoral injection of OK-432 (OK-432 it), a bacterial biological response modifier, in patients with gastric cancer. The 10-year survival and disease-free survival were examined and analysis of the factors showing survival benefit was performed. 370 patients who had undergone curative resection of gastric cancer were enrolled in this study and followed up for 10 years postoperatively. Patients were randomized into either an OK-432 it group or a control group. Ten Klinishe Einheit (KE) of OK-432 was endoscopically injected at 1 to 2 weeks before the operation in the OK-432 it group. Both groups received the same adjuvant chemoimmunotherapy consisting of a bolus injection of mitomycin C (0.4 mg kg(-1) i.v.) and administration of tegafur and OK-432 from postoperative day 14 up to 1 year later. Tegafur (600 mg day(-1)) was given orally and OK-432 (5 KE/2 weeks) was injected intradermally for a maintenance therapy. The TILs grades in resected tumour specimens and presence of metastasis and metastatic pattern in dissected lymph nodes were examined. Multivariate analysis was performed to determine the efficacy of OK-432 it on prognostic factors. All patients were followed up for 10 years. The overall 5- and 10-year survival rates and disease-free survival rates of the OK-432 it group were not significantly higher than those of the control group. However, OK-432 it significantly increased the 5- and 10-year survival rates of patients with stage IIIA + IIIB, moderate lymph node metastasis (pN2), and positive TILs. OK-432 it was most effective at prolonging the survival of patients who had both positive TILs and lymph node metastasis. The OK-432 it group with positive TILs showed a significant decrease in metastatic lymph node frequency and in the number of lymph node micro- metastatic foci when compared to the control group. This study showed that only one time preoperative OK-432 it, particularly when it triggers TILs, is effective for reduction of regional lymph node metastasis. OK-432 it probably acts partly by eliminating micro-metastatic foci in lymph nodes. Preoperative intratumoral injection of OK-432 is technically very easy and has no serious adverse effects, so it is a promising form of neoadjuvant immunotherapy for advanced gastric cancer.

Adult↗
PubMed2001

Changes in occlusal state of patients with mandibular prognathism after orthognathic surgery: a pilot study.

This study examined the occlusal state of patients with mandibular prognathism and compared it with that of adults with normal occlusion (controls). It also examined changes in occlusal state after orthognathic operations in these patients. The values of occlusal contact area and bite force in patients before operation were significantly lower than in controls, and occlusal pressure in patients was higher than in controls. The occlusal contact area and bite force of the patients 1 month after the operation had decreased to below preoperative values. These values 12 months after the operation had increased by 2.0 and 1.8 times in women and 1.4 and 1.4 times in men, respectively, compared with preoperative values. However, absolute values remained extremely low compared with those of controls. In contrast to the above, occlusal pressure reached its maximum value 1 month after the operation and at 12 months it was close to the value for controls.

Adult↗
PubMed2001

Relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism in humans.

BACKGROUND: Nicotine is mainly metabolized to cotinine by cytochrome P450 (CYP) 2A6. Previously, we found that the CYP2A6 gene was deleted homozygously in one subject who was deficient in cotinine formation from nicotine. OBJECTIVE: Our objective was to clarify the relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism. METHODS: Nicotine was administered to 92 healthy Japanese subjects in the form of 1 piece of nicotine gum to investigate the potency of nicotine metabolism. The cotinine-nicotine ratio of the plasma concentration 2 hours after chewing was calculated as an index of nicotine metabolism. The genotypes of CYP2A6 gene, CYP2A6*1A, CYP2A6*1B, CYP2A6*2, CYP2A6*3, CYP2A6*4, and CYP2A6*5, were determined with polymerase chain reaction-restriction fragment length polymorphism. RESULTS: A large interindividual difference in nicotine metabolism was observed. Allele frequencies of CYP2A6*1A, CYP2A6*1B, and CYP2A6*4 were 42.4%, 37.5%, and 20.1%, respectively. The CYP2A6*2, CYP2A6*3, and CYP2A6*5 alleles were not found. Three subjects genotyped as CYP2A6*4/CYP2A6*4 were completely deficient in cotinine formation. The heterozygotes of the CYP2A6*4 allele tend to show lower capacities for cotinine formation. The subjects with CYP2A6*1A/CYP2A6*1B appeared to have higher capacities of cotinine formation than subjects with CYP2A6*1A/CYP2A6*1A, although the difference was not significant. The probit plot of the cotinine-nicotine ratio was not linear; this possibly indicated the existence of a novel mutation in the CYP2A6 gene genotyped as CYP2A6*1B/CYP2A6*4. CONCLUSIONS: The relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism in humans was proved.

Administration, Oral↗
PubMed2001

Predominant inner-half wall thickening of left ventricle is attenuated in dilated cardiomyopathy: an application of tissue Doppler tracking technique.

The importance of the inner half (IH) of the left ventricular (LV) wall has been reported in hearts that contract normally. However, it is difficult to verify this fact in an in vivo human heart with clinical echocardiography. By using a recently developed tissue Doppler tracking technique, we could assess the systolic wall thickening of the IH and outer half (OH) of the LV wall in 11 normal and 7 dilated cardiomyopathic hearts. Percent wall thickening and the fractional contribution of the IH and OH to the transmural wall thickening were calculated. In healthy subjects, percent wall thickening of the IH, OH, and transmural wall of the left ventricle were 75.8% +/- 24.1%, 39.4% +/- 14.4% (P <.001 versus IH), and 57.6% +/- 17.6%, respectively. In patients with dilated cardiomyopathy, those values were 31.3% +/- 17.1%, 31.2% +/- 20.1% (not significant versus IH), and 31.2% +/- 16.5%, respectively. On the other hand, the fractional contributions of the IH and OH were 66.2% +/- 7.7% and 33.8% +/- 7.7% (P &lt.01 versus IH) in healthy subjects and 50.5% +/- 11.8% and 49.5% +/- 11.8% (not significant versus IH) in patients with dilated cardiomyopathy. Specifically, the IH contributed to the transmural wall thickening nearly twice as much as the OH did in healthy subjects, however, the predominance of IH contribution was attenuated in dilated cardiomyopathy. The tissue Doppler tracking technique is useful in assessing the IH and OH LV wall thickening separately in the clinical situation.

Adult↗
PubMed2001

The importance of pulmonary venous flow measurement for evaluating left ventricular end-diastolic pressure in patients with coronary artery disease in the early stage of diastolic dysfunction.

Transmitral flow pattern assessed by pulsed Doppler echocardiography is widely used to evaluate left ventricular end-diastolic pressure (LVEDP). A restrictive mitral flow pattern is well recognized as a finding of severely elevated LVEDP. On the other hand, an abnormal relaxation pattern can be interpreted many ways. For example, some patients who display an abnormal relaxation pattern have a mild impairment of left ventricular (LV) relaxation as a result of aging, and others have severely impaired LV diastolic function. To evaluate LVEDP in patients with abnormal relaxation mitral filling patterns, we studied 55 patients who had coronary artery disease with abnormal relaxation pattern who underwent elective cardiac catheterization. We recorded the transmitral and pulmonary venous flow velocity curves and measured the duration of the mitral A wave (MAd) and pulmonary venous reversal wave during atrial contraction (PAd). Positive correlations were found between PAd and LVEDP (r = 0.65, P <.01) and between PAd-MAd and LVEDP (r = 0.7, P <.0001); however, MAd was not significantly correlated with LVEDP. In conclusion, PAd must be measured for an accurate evaluation of LV end-diastolic pressure in patients with an abnormal relaxation pattern in the transmitral flow velocity curve.

Aged↗
PubMed2001

New method of on-line quantification of regional wall motion with automated segmental motion analysis.

We have recently developed an automated segmental motion analysis (A-SMA) system, based on an automatic "blood-tissue interface" detection technique, to provide real-time and on-line objective echocardiographic segmental wall motion analysis. To assess the feasibility of A-SMA in detecting regional left ventricular (LV) wall motion abnormalities, we performed 2-dimensional echocardiography with A-SMA in 13 healthy subjects, 22 patients with prior myocardial infarction (MI), and 9 with dilated cardiomyopathy (DCM). Midpapillary parasternal short-axis and apical 2- and 4-chamber views were obtained to clearly trace the blood-tissue interface. The LV cavity was then divided into 6 wedge-shaped segments by A-SMA. The area of each segment was calculated automatically throughout a cardiac cycle, and the area changes of each segment were displayed as bar graphs or time-area curves. The systolic fractional area change (FAC), peak ejection rate (PER), and filling rate (PFR) were also calculated with the use of A-SMA. In the control group, a uniform FAC was observed in real time among 6 segments in the short-axis view (60% +/- 10% to 78% +/- 9%), or among 5 segments in either the 2-chamber (59% +/- 12% to 75% +/- 16%) or 4-chamber view (58% +/- 13% to 72% +/- 12%). The variations of FAC, PER, and PFR were obviously decreased in infarct-related regions in the MI group and were globally decreased in the DCM group. We conclude that A-SMA is an objective and time-saving method for assessing regional wall motion abnormalities in real time. This method is a reliable new tool that provides on-line quantification of regional wall motion.

Adult↗
PubMed2001

The induction of angiogenesis by the implantation of autologous bone marrow cells: a novel and simple therapeutic method.

BACKGROUND: Bone marrow contains many kinds of primitive cells that could differentiate to endothelial cells and secrete several growth factors. In the current study, we attempted to induce therapeutic angiogenesis by implanting autologous bone marrow cells (BMCs) and using a rat ischemic hind limb model. METHODS: BMCs were prepared by removing red blood cells. A rat ischemic hind limb model was made by the ligation of the left femoral artery and its branches. BMCs were injected into 7 points of the ischemic muscles. To assess angiogenesis, a microangiogram, laser Doppler, and histologic evaluation were performed after the surgical procedure. RESULTS: A microangiogram and histologic evaluation showed that angiogenesis was significantly induced in the ischemic hind limb by the implantation of BMCs. Laser Doppler imaging analysis showed that blood flow was significantly increased after implantation of BMCs. Some implanted BMCs were stained positively with CD31 and vascular endothelial-cadherin (VE-cadherin), which might have been incorporated into the vasculature. The condition of ischemia caused an elevation in the level of basic fibroblast growth factor in the ischemic muscle and also in interleukin-1beta derived from the implanted BMCs, which might contribute to angiogenesis. CONCLUSION: These findings indicate that autologous bone marrow implantation may be a novel and simple method for inducing therapeutic angiogenesis.

Animals↗
PubMed2001

Successful management of tracheo-innominate artery fistula with endovascular stent graft repair.

Tracheo-innominate artery fistula is a highly lethal complication after tracheostomy. A 37-year-old man who had undergone a tracheostomy 14 years earlier because of dysphagia after brain surgery had a tracheo-innominate artery fistula with exsanguinating hemorrhage from his tracheostomy site. After temporary control of the bleeding, a stent graft was implanted in the innominate artery through the brachial artery. The patient recovered uneventfully and remained well 14 months after the procedure, with no sign of infection. Endovascular stent grafting may be the treatment of choice for patients with tracheo-innominate artery fistula.

Adult↗
PubMed2001

Lipopolysaccharide of Haemophilus influenzae induces interleukin-5 mRNA expression in human peripheral blood mononuclear cells.

Haemophilus influenzae is the bacterial species most often isolated from sputum of patients with chronic obstructive pulmonary disease (COPD). In this study, we examined the induction of interleukin-5 (IL-5) mRNA expression in human peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide (LPS) from H. influenzae to try to predict the effect of H. influenzae infection on the eosinophilic inflammation in COPD. Detection of IL-5 mRNA by RT-PCR showed that LPS from H. influenzae induced IL-5 mRNA expression in PBMC at a concentration of 1 microg/ml. Furthermore, the level of expression of IL-5 mRNA induced by LPS correlated with the amount of IL-5 protein in the culture supernatant. Inhibition of LPS-induced IL-5 mRNA expression by anti-CD14 antibody and diminution of this in a CD3(+) -cell-depleted fraction of PBMC, respectively, suggested that CD14 molecules were required for the increase in IL-5 mRNA and that T lymphocytes were the principal source of IL-5 mRNA expression in PBMC. Briefly, the IL-5 mRNA expression induced by LPS would be based on LPS-activated monocytes interacting with T lymphocytes to produce IL-5. These results may explain the role that colonization with H. influenzae plays in eosinophilic inflammation in patients with COPD.

Base Sequence↗
PubMed2001

Papillary carcinoma of the thyroid with distant metastases to the cerebrum: a case report.

Cerebral metastases from papillary carcinoma of the thyroid are a very uncommon condition, but such metastases behave more aggressively and show poor prognosis. These metastases almost always involve concomitant lung or bone metastases which may be the first metastatic sites. Here we report a 53-year-old man with diffuse goiter and cervical lymphadenopathy who developed symptoms of elevated intracranial pressure. Computed tomography demonstrated ring-enhanced lesions showing a severe mass effect in the right cerebrum and a nodule in the right thyroid gland accompanied by swollen lymph nodes. Biopsied specimens of the thyroid nodule demonstrated malignant cells of papillary carcinoma. Surgical excision of the metastatic brain lesions was followed by total thyroidectomy with regional lymphadenectomy. Histological examinations confirmed that the patient had cerebral metastases from papillary carcinoma of the thyroid without other distant metastasis. Neurological abnormality disappeared after surgery and treatment with radioactive iodine (131I) and oral thyroxine were initiated thereafter. This case suggests that the thyroid gland is potentially a primary source of metastatic brain carcinoma. Moreover, early detection of cerebral metastases is crucial because these metastatic lesions can be life threatening, in contrast to the relatively less severe clinical course of this malignancy unless it is associated with any distant metastasis.

Brain Neoplasms↗
PubMed2001

A family of multiple endocrine neoplasia type 2A with the RET proto-oncogene mutation in codon 618 (Cys-->Arg).

Multiple endocrine neoplasia type 2 (MEN-2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia or adenoma of the parathyroid gland with hyperparathyroidism. Recent genetic studies have identified the presence of germline missense mutations in the RET proto-oncogene in almost 100% of MEN-2 patients. We report here three generations of one MEN-2 family with rare missense mutation at codon 618 (Cys-->Arg) of the RET proto-oncogene. The first patient was surgically treated at the age of 63 years but died of bone metastasis. His two children (29-year-old daughter and 25-year-old son) were treated surgically for MTC and neck lymph node metastasis. Germline mutations of the RET proto-oncogene of these three MTC patients and two children of the 29-year-old daughter (9-year-old female and 7-year-old male) were examined. Three MTC patients and the 9-year-old female possessed the mutation. The phenotype of the family with this rare point mutation of the RET proto-oncogene is reported.

Adult↗
PubMed2001

Leiomyosarcoma arising in a remnant esophagus after esophagectomy: a case report.

We report an extremely rare case of leiomyosarcoma arising from a remnant esophagus. A 52-year-old Japanese man was referred to our hospital for treatment of a tumor arising from the remnant esophagus. Four years earlier, he underwent a subtotal esophagectomy for esophageal squamous cell carcinoma (well differentiated squamous cell carcinoma, T1N0M0 Stage I) located in the lower esophagus. After preoperative studies, partial esophagectomy with laryngeal preservation and reconstruction using a free graft from the jejunum were performed. Histopathological and immunohistochemical examination revealed leiomyosarcoma without metastasis. Immunohistochemical examination showed that most tumor cells were positive for smooth muscle actin and vimentin, but were negative for cytokeratin and S100. The deeply biopsied specimens are helpful for preoperative histological diagnosis. Mitotic activity has been considered an important criterion of malignancy. However, some cases with minimal mitosis in the tumor grow rapidly and were associated with poor prognosis. Therefore, we advocate that the clinical behavior is the only true indication of malignancy. We also provide a review of 64 cases of esophageal leiomyosarcoma reported in the Japanese literature with available data between 1969 and 1999, including the present case, and discuss their clinicopathological features. Asynchronous occurrence of leiomyosarcoma and squamous cell carcinoma in the esophagus is most unusual and has never been reported. Patients with infiltrating type leiomyosarcoma measuring more than 5 cm in diameter tend to have a poor prognosis. Chemotherapy did not exhibit any survival benefits. In the present patient, no recurrence has been noted for 23 months after surgery.

Carcinoma, Squamous Cell↗