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Biomedical subjects

T Fukumoto

Publications and source records attributed to T Fukumoto.

At least 73 records · Page 4Linked to original sources
PubMed1997

Lymph node and perinodal tissue tumor involvement in patients with esophagectomy and three-field lymphadenectomy for carcinoma of the esophagus.

BACKGROUND: Lymph node metastasis is a definitive prognostic factor; however, perinodal fat tumor invasion has not been fully elucidated. METHODS: Periesophageal nodes and the surrounding fibrofatty tissue obtained from 131 patients who underwent esophagectomy were examined. RESULTS: Of 9,789 nodes removed, 645 (6.6%) demonstrated invasion and 143 (1.5%) showed perinodal involvement. Of 131 patients 97 (74.0%) had lymph node involvement and 43 (32.8%) had perinodal fat involvement. The incidence of perinodal tissue involvement correlated significantly with the number of nodes involved; 23 (42.6%) of 54 patients with a total of 1-8 nodes involved and 19 (95.0%) of 20 patients with 9 or more involved nodes had perinodal involvement. The 5-year survival for 33 patients without involved nodes or perinodal tissue extension was 59.7%, compared to 14.0% for 43 patients with perinodal fat involvement. CONCLUSION: Perinodal tissue carcinoma into the periesophageal fibrofatty tissue was a decisive prognostic factor in patients with curative resection for esophageal carcinoma.

Adipose Tissue↗
PubMed1997

Detection and characterization of IL-1 receptor antagonist in tissues from healthy rabbits: IL-1 receptor antagonist is probably involved in health.

Interleukin 1 (IL-1) is postulated to function in maintaining homeostasis, however, over-action of this cytokine may lead to disruption of homeostasis due to it's wide spectrum of activities. To understand the endogenous regulation of this cytokine, we examined the existence of IL-1 receptor antagonist (IL-1Ra) in tissues from healthy rabbits. IL-1Ra was constitutively produced in all tissues examined (lung, liver, spleen, thymus, caecum, skin, kidney, heart, and brain), as estimated by ELISA. Immunoprecipitation, RT-PCR and immunohistochemical studies indicated that all tissues produced secreted form of IL-1Ra (sIL-1Ra), whereas thymus, caecum, skin and kidney produced both sIL-1Ra and intracellular of IL-1Ra. All tissue IL-1Ra purified using anti-IL-1Ra IgG affinity chromatography had inhibitory activity on the IL-1-induced thymocyte proliferative response, and the activity was totally abolished by anti-IL-1Ra mAb. No IL-1 activity was detected in any tissues except skin and heart, however, after preincubation of the samples with anti-IL-1Ra, the activity was first visible in the tissues. Under these conditions, IL-1 activity in skin and heart was enhanced to 170% and 280%, respectively. Taken together, we conclude that tissue IL-1Ra is involved in health maintenance by masking co-existing IL-1 activity present in tissues.

Animals↗
PubMed1997

Pharmacokinetics of adriamycin and cisplatin for anhepatic chemotherapy during liver transplantation.

We investigated the pharmacokinetics of cytotoxic anticancer agents administered under anhepatic conditions. Beagle dogs underwent either a sham operation consisting of laparotomy only (control group, n = 11) or a laparotomy and total hepatectomy under venovenous bypass (anhepatic group, n = 12). Each dog received a bolus intravenous injection of either Adriamycin (1 mg/kg) or cisplatin (1 mg/kg). The plasma and urine concentrations of each drug were measured at intervals for up to 2 h after drug injection. The dogs given Adriamycin were then sacrificed to determine tissue drug concentrations in the liver (controls only), spleen, kidney, heart, lung, skeletal muscle and small intestine. The control and anhepatic groups showed similar Adriamycin profiles during the initial 5 min after drug injection. However, subsequently, the plasma Adriamycin concentrations remained persistently higher in the anhepatic dogs than in the controls, yielding a two-fold elevation of the mean area under the concentration-time curve in the anhepatic group (P < 0.01 vs controls). The renal clearance values did not significantly differ between the two groups. The tissue Adriamycin concentrations in all measured organs, excluding the liver, were higher in the anhepatic group than in the controls. In a second set of experiments with cisplatin, the plasma platinum concentrations did not significantly differ between the two groups throughout the time course. However, the renal clearance of platinum in the anhepatic dogs showed a fourfold increase compared with that in the controls (P < 0.01). These pharmacokinetic data suggest that Adriamycin carries the risk of increased systemic toxicities, while cisplatin may be associated with increased renal toxicity when administered during the anhepatic period of liver transplantation.

Animals↗
PubMed1997

Single catheter technique of hepatic venous isolation and extracorporeal charcoal hemoperfusion for malignant liver tumors.

BACKGROUND: A single catheter technique of hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) using a 4-lumen/2-balloon (4L-2B) catheter was developed to perform high-dose intra-arterial chemotherapy of the liver. Herein we report the technique, safety, and pharmacokinetics of this system in comparison with the original double-balloon technique. PATIENTS AND METHODS: Sixteen patients with malignant liver tumors were treated by hepatic arterial infusion (HAI) with adriamycin at a dose of 100 mg/m2 under HVI-CHP. Seven patients underwent HVI-CHP by the double-balloon technique (group A), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other nine patients were treated by the single catheter technique (group B). In group B, hepatic effluent was isolated by balloon inflations and directed to filters through fenestrations of one major lumen of a 4L-2B catheter. The filtered blood was returned straight to the right atrium through the other major lumen of the catheter. RESULTS: All patients in group A had a smooth stepwise induction of HVI-CHP, whereas one of nine patients in group B developed severe hypotension requiring interruption of HVI. The hepatic venous flow rate in group B during HVI-CHP was significantly higher than that in group A (P < 0.05). Systemic adriamycin exposure, as assessed by the area under the time concentration curve in systemic serum, was significantly higher in group A compared to that in group B (P < 0.01). CONCLUSIONS: The single catheter technique is hemodynamically tolerable and feasible in the majority of patients with malignant liver tumors. In view of systemic drug exposure, the single catheter technique is superior to the original double-balloon technique.

Aged↗
PubMed1997

Neonatal lupus erythematosus: analysis of HLA class II alleles in mothers and siblings from seven Japanese families.

BACKGROUND: Neonatal lupus erythematosus (NLE) is a syndrome characterized by dermatitis and congenital heart block. The disease is mostly associated with transplacental passage of maternal anti-Ro(SS-A) or anti-La(SS-B) antibodies. Maternal HLA-DR3 and DQ2 alleles are associated with NLE in white and North American black populations. OBJECTIVE: We sought evidence of a potential genetic disposition to NLE in mothers with a relatively homogeneous ethnic background. METHODS: Class II human major histocompatibility complex HLA-DRB1, DQA1, DQB1, and DPB1 alleles were determined by polymerase chain reaction-restriction fragment length polymorphism in anti-Ro(SS-A)-positive mothers as well as in infants from seven Japanese families with siblings concordant or discordant for disease expression of NLE. RESULTS: All seven mothers had two or three DQ alleles of DQA1 and DQB1 possessing specific amino acid residues, which are reportedly associated with anti-Ro(SS-A) autoantibody response in white and black populations. There was no class II HLA profile that distinguished disease manifestations of NLE in infants. CONCLUSION: The HLA class II allele associations with anti-Ro(SS-A) autoantibodies that have been noted in other ethnic groups were also found in Japanese anti-Ro(SS-A)-positive mothers whose infants had NLE, suggesting shared susceptibility factors across racial barriers in maternal predisposition to Ro(SS-A) autoimmune response.

Disease Susceptibility↗
PubMed1997

Extranodal connective tissue invasion and the expression of desmosomal glycoprotein 1 in squamous cell carcinoma of the oesophagus.

We investigated extranodal connective tissue involvement (ECTI) in 39 patients with oesophageal carcinoma. Both the primary tumour and ECTI were immunohistochemically examined using the monoclonal antibody 32-2B for desmosomal glycoprotein 1 (DG1). Connective tissue carcinoma deposits were identified as cells within small lymph nodes, as lymphatic or venous vessel invasion or as widespread invasion beyond the capsule of metastatic lymph nodes. These histological findings were present in at least one area in 20 of 39 patients (51.3%). DG1 immunostaining intensity by tumour was graded as DG1 (++), DG1 (+) or DG1 (-). DG1 (+) or DG1 (-) primary tumours demonstrated lymph node metastases and ECTI more frequently than DG1(++) tumours (P<0.05). Among 17 patients in whom DG1 immunohistochemistry was performed on ECTI, there were three DG1(++), five DG1(+) and nine DG1(-) patients. The DG1 expression of ECTI was equal to or less intense than the primary tumour. These results indicate that reduction or loss of DG1 expression may promote ECTI and lymph node metastases. One should be aware of the potential for ECTI in oesophageal carcinomas. In the future, adjuvant therapy may be advisable for some oesophageal carcinomas based on the phenotype of individual cancer cells, including expression of DG1.

Aged↗
PubMed1997

Synchronous and metachronous carcinomas of the esophagus and head and neck.

We retrospectively analyzed the clinicopathologic findings, treatment and outcome of 22 patients with synchronous or metachronous carcinomas of the esophagus and head and neck. The patients with metachronous cancers in whom esophageal cancer occurred first had either an early-stage esophageal carcinoma or only one positive lymph node. Similarly, five of 10 patients with metachronous cancers in whom head and neck cancer was the first tumor had early-stage esophageal carcinomas. The esophageal lesion was mucosal carcinoma in four patients which was found by endoscopy with the iodine dye method. In the patients with synchronous cancers either one or both carcinomas were advanced, and the prognosis of these patients was poor compared with those of patients with metachronous carcinomas. Accordingly, endoscopic surveillance for early detection of metachronous lesions are encouraged.

Adult↗
PubMed1997

Pleuropulmonary blastoma: fluorescence in situ hybridization analysis indicating trisomy 2.

We report a case of pleuropulmonary blastoma occurring in the right upper lobe and pleura of a 29-month-old boy. Histologically, the tumor was composed of undifferentiated mesenchymal cells with occasional rhabdomyoblastic and chondroid differentiation. Immunohistochemical analysis showed vimentin immunoreactivity in most of the tumor cells, myoglobin, desmin, and actin in the rhabdoid cells, and S-100 protein in the chondroid cells. Fluorescence in situ hybridization (FISH) analysis showed trisomy 2 and normal chromosomal copy numbers for chromosomes 7, 12, 17, 18, and X in the majority of the tumor cell nuclei. The identification of trisomy 2 in the current pleuropulmonary blastoma confirms a previous cytogenetic finding of chromosome 2 abnormality with cultured metaphase cells of a similar case, indicating that the acquisition of an additional chromosome 2 copy in pleuropulmonary blastoma is a nonrandom chromosomal alteration and that pleuropulmonary blastoma is cytogenetically distinct from pulmonary blastoma in which chromosome 2 is bisomic. It is also suggested that pleuropulmonary blastoma may have an intimate tumorigenetic relationship with embryonal rhabdomyosarcoma.

Actins↗
PubMed1997

Neonatal lupus erythematosus: HLA-DR and -DQ distributions are different among the groups of anti-Ro/SSA-positive mothers with different neonatal outcomes.

Neonatal lupus erythematosus (NLE) is an antibody-mediated disorder of infants characterized by two major clinical manifestations; cutaneous lupus lesions and congenital heart block (CHB). The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. There is a tendency for the same disease expression to occur within a sibship. To reveal a possible association of class II MHC genes with maternal anti-Ro/SSA autoimmune responses and neonatal outcomes in NLE with a relatively homogeneous ethnic background, haplotype, and allele distributions were analyzed based on the PCR-RFLP results in 26 Japanese anti-Ro/SSA-positive mothers from three groups defined by neonatal outcomes. The results were as follows: (i) maternal HLA-DR5 haplotype DRB1*1101-DQA1*0501-DQB1*0301 and individual class II alleles making up this haplotype were significantly associated with neonatal cutaneous lupus but not CHB. Conversely, maternal HLA-DQB1*0602 carried on HLA-DR2 haplotypes was associated with CHB but not cutaneous NLE; (ii) HLA-DQA1 alleles with glutamine at position 34 of the first domain, which have reportedly been associated with the autoimmune responses to Ro/SSA antigens in other ethnic groups, were increased in the mothers of infants with cutaneous involvement; and (iii) there was no particular class II HLA profile that distinguished the disease manifestations in infants. These findings suggest that specific maternal MHC class II genes might correlate with specific neonatal outcomes in NLE.

Adult↗
PubMed1997

HLA-DRB1*04 and DRB1*14 alleles are associated with susceptibility to pemphigus among Japanese.

It has previously been demonstrated that susceptibility to pemphigus vulgaris is associated with human leukocyte antigen (HLA)-DR4 serologic specificity among Ashkenase Jews, and with DR4 as well as DR6 (DR14) in other ethnic groups. We genotyped HLA-DRB1, DQA1, DQB1, and DPB1 alleles in 16 patients with pemphigus by polymerase chain reaction-restriction fragment length polymorphism, to find evidence of potential HLA class II allele associations with pemphigus in Japanese patients who have a relatively homogeneous ethnic background. All nine patients with pemphigus vulgaris and five of seven patients with pemphigus foliaceus carried one or two alleles of HLA-DRB1*04 (*0403, *0406) and HLA-DRB1*14 (*1401, *1405, *1406) subtypes. Sequence analysis of these DRB1*04 and DRB1*14 alleles revealed the amino acid homology of phenylalanine at position 26 and valine at position 86 with the DRB1*0402 allele that reportedly confers a strong susceptibility to pemphigus vulgaris in Ashkenazi Jews. Thus our findings, together with previous HLA studies on pemphigus vulgaris patients of different ethnic groups, suggest that HLA-DRB1*04 and DRB1*14 alleles are commonly associated with pemphigus vulgaris across racial barriers. These HLA-DRB1 alleles are likely to be also associated with pemphigus foliaceus. Further studies on more diverse ethnic populations will be helpful in determining the significance of the association between certain amino acid residues of the class II molecules and disease susceptibility to pemphigus vulgaris as well as pemphigus foliaceus.

Adult↗
PubMed1997

Expression of ICAM-1 in implanted primary and metastatic squamous cell carcinomas in rats.

FF6 tumor cells are derived from a spontaneous rat squamous cell carcinoma (SCC) which originally arose in the facial skin of a DA rat. In this study, FF6 tumor cells were implanted into rat oral mucosa to establish an ex vivo metastatic model. We analyzed the expression of intercellular cell adhesion molecule-1 (ICAM-1) in the implanted primary and metastatic FF6 tumors by immuno-staining with a monoclonal antibody (mAb) against ICAM-1. The implanted primary FF6 cells showed strong expression of ICAM-1, whereas the tumor cells of metastatic lesions showed weak or negative expression of ICAM-1. By immunostaining with mAb OX6, a number of MHC class II-positive macrophages were detected in tumor mesenchyme and surrounding the metastatic foci. These results suggested that the local immune reaction in the lymph node influenced the expression of ICAM-1 on tumor cells, and that MHC class II-positive macrophages may play a role in transplanted tumor growth and metastases.

Animals↗
PubMed1997

Recognition of a special membrane antigen of squamous cell carcinoma in rats with a monoclonal antibody UB23.

This article describes the recognition of a special membrane antigen of the rat squamous cell carcinoma (SCC) by a monoclonal antibody (mAb), UB23, and the characterization of the UB23 antigen expression in the implanted primary and metastatic SCC in rat models. The mAb UB23 was raised against the FF6 tumor, a well-differentiated rat SCC, and it recognized the 120- to 130-kD cell surface antigen in FF6 tumor cells. The UB23 antigen was found in frequently observed small 'basal' cells but not in keratinocytes, and an increased expression was seen in the cells at the interface with peritumoral stroma in both the implanted primary FF6 tumors and metastases. These results indicated that the UB23 antigen is closely related with the cell differentiation and invasion of FF6 cells, and could be useful for analyzing the mechanism of differentiation, invasion and metastasis of SCC in animal models.

Animals↗
PubMed1997

Relationship between ultrasound assessment of arterial wall properties and blood pressure.

Physical properties of an artery can be described in terms of stiffness, distensibility, and compliance. Changes in these properties can predict atherosclerosis disease, but it is necessary to identify an index that is independent of changes in blood pressure. We measured common carotid artery diameter and pulsatile change with an ultrasonic phase-locked, echo-tracking system in 7 subjects whose mean brachial blood pressure had varied 15 mm Hg or more within a month. Patients taking antihypertensive agents were excluded from the study. We measured changes in arterial diameter (n = 41) at least four times during the study period and calculated the pressure-strain elastic modulus (Ep), distensibility coefficient (DC), cross-sectional compliance (CC) and stiffness parameter (beta) from inner diameter, its pulsatile change, and blood pressure. The correlation coefficients of mean blood pressure with each index are as follows: Ep, 0.53; DC, 0.58; CC, 0.63; beta, 0.21. When mean blood pressure increased 1 mm Hg, the change in each index at 100 mm Hg was as follows: Ep, 1.48 +/- 1.30%; DC, -1.05 +/- 0.97%; CC, -0.69 +/- 0.90%; beta, 0.45 +/- 1.11%. Among the four indices that measure the properties of the arterial walls, stiffness parameter beta was the least dependent on blood pressure. Thus, it appears to have usefulness as an index of arterial wall sclerosis.

Aged↗
PubMed1997

Precise analyses of the structure of the thymus for establishing details of the mechanisms underlying thymocyte proliferation and maturation.

Details of thymocyte proliferation and maturation are important for understanding the variability of T cell functions. The following aspects need to be clarified in this context: 1) Ascertaining why hematopoietic committed pre-T cells migrating in the blood stream are trapped and proliferate in the subcapsular region of the thymus. Further morphological and functional studies of stromal cells in situ in the thymus should be conducted. The factors responsible for thymocyte proliferation should be also analysed. 2) How phenotypic maturation of thymocytes takes place and how T-cell receptor (TCR) expression is processed and controlled. 3) Subsequently, how does the selection of thymocytes take place? Is negative selection in fact responsible for the unresponsiveness of the body to self antigens? Further morphological analyses of thymic epithelial cells, thymocytes themselves and macrophages need to be conducted, together with immunohistochemical analyses using many monoclonal antibodies directed against these cells and the extracellular matrix, in order to analyse the cellular dynamics and cell-to-cell interactions occurring in thymus tissues in situ. 4) How mature thymocytes migrate to the periphery: Perivascular structures and the cells accumulating in this space should be intensively analysed morphologically and phenotypically. Lymphatic structures related to the thymus tissues also remain to be studied. To understand these questions, several useful experimental systems can also be employed: 1) Phylogenetical analyses, 2) ontogenical analyses, 3) thymus tissues regenerating from radiation or thymotoxic drugs, 4) thymomas, and 5) thymus tissues from transgenic animals. These important problems could be further studied in such experimental models both morphologically and immunohistochemically, since many useful tools are now available for studies of phenotypic and other markers of thymocytes and thymic epithelial cells. Subsequently, further detailed analyses of thymic structures may shed more light on the mechanisms underlying thymocyte proliferation and maturation.

Animals↗
PubMed1997

Morphological and flow cytofluorometrical analyses of regenerated rat thymus after irradiation.

Reconstituted rat thymuses were studied by immunohistochemistry, transmission electron microscopy (TEM) and flow cytofluorometry on days 0, 1, 2, 3, 5, and 7 after whole-body sublethal irradiation (6 Gy). One day after irradiation, numerous apoptotic cells were seen in the cortical thymus; the percentage of the sub-G1 peak representing apoptotic cells was 8.9% in the DNA content histogram of cytofluorometry. On day 3, the thymic structure had been destroyed and no distinction was drawn between the cortex and medulla. In this stage, few thymocytes but many macrophages were present, and the percentage of the sub-G1 peak reached a peak at 13.0%. Bromodeoxyuridine (BrdU) incorporated cells gradually increased after irradiation, and immunohistochemically numerous apoptotic cells were found primarily in the cortex on day 7. These thymocytes showed some levels of electron density of the nucleus as revealed by TEM. The percentage of S phase cells did not change markedly (20-30%) based on one-color DNA content histograms, but the percentage of early S and S phase cells was extremely high on day 7 (70%). These data indicate that a part of DNA synthetic cells may result in apoptosis. The combination of immunohistochemistry, TEM and flow cytofluorometry to analyze DNA content and BrdU incorporation proved a useful tool for investigating the reconstituted thymus.

Animals↗
PubMed1997

Neonatal lupus erythematosus: studies on HLA class II genes and autoantibody profiles in Japanese mothers.

Neonatal lupus erythematosus (NLE) is a rare disorder of neonates characterized by two major clinical manifestations: congenital heart block and cutaneous lupus lesions. The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. To clarify possible class II HLA associations with maternal autoantibody responses, haplotypic and allelic distributions, along with the polymorphism of the MHC class II HLA alleles, were analyzed based on PCR-RFLP results in 25 Japanese mothers of two groups defined by precipitating autoantibody profiles. Among mothers with both anti-Ro/SSA and anti-La/SSB antibodies, but not those with anti-Ro/SSA alone, the class II haplotypes DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*08032-DQA1*0103-DQB1*0601 as well as individual class II alleles DRB1*1101, DRB1*08032 and DQB1*0301 showed significantly increased frequencies compared to those in normal controls. All anti-Ro/SSA and anti-La/SSB positive mothers carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the DRB1 chain. These mothers also carried homozygous or heterozygous DQ6 and DQ3 alleles that shared the same amino acid residues at positions 27-36 and 71-77 of hypervariable regions of the DQB1 chain. Furthermore, all mothers with both anti-Ro/SSA and anti-La/SSB were homozygous for DPB1*0501. Nine of 10 anti-Ro/SSA and anti-La/SSB-positive mothers, but only 6 of 15 mothers with anti-Ro/SSA alone, had affected infants. Thus, our findings suggest that there may be immunogenetic differences among mothers according to their autoantibody profiles, and that mothers with both anti-Ro/SSA and anti-La/SSB are more likely to have infants with NLE than mothers with anti-Ro/SSA alone.

Animals↗