Cytokine mRNA expression in the liver after administration of donor leukocytes.
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Biomedical subjects
Publications and source records attributed to K Hatakeyama.
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BACKGROUND: Great controversy exists concerning the adequate extent of esophagectomy for cure in patients with esophageal cancer. Extended radical esophagectomy combined with three-field lymphadenectomy has been performed to improve the cure rates for patients with the disease in Japan. The purposes of this study were to assess the mortality and morbidity rates after extended radical esophagectomy and to determine the oncologic indications for this procedure. STUDY DESIGN: We reviewed 190 patients who underwent extended radical esophagectomy for invasive esophageal cancer. The procedures were performed prospectively between 1982 and 1996. RESULTS: The 30-day mortality, in-hospital mortality, and morbidity rates were 1.6%, 4.7%, and 58.4%, respectively. The most common postoperative complication was vocal-cord paralysis (45.3%), followed by major pulmonary complications (21.6%). The overall survival rate for the 190 patients was 41.5% at 5 years, with a median followup period of 61 months. Some subgroups of patients had an extremely poor prognosis despite extended radical esophagectomy. Survival was < or = 5 years in all patients with five or more positive nodes; all patients with simultaneous metastases to the cervical, mediastinal, and abdominal lymph nodes; and all patients with cervical metastases from a lower esophageal tumor. CONCLUSIONS: Extended radical esophagectomy is potentially associated with high morbidity rates although the mortality rates are acceptable, suggesting the necessity of careful patient selection. This procedure is indicated oncologically only for patients with four or fewer metastatic nodes or with metastases confined to one or two of the three anatomic compartments (neck, mediastinum, and abdomen) from upper or midesophageal tumors.
Diarrhea virus of infant mice (DVIM) is a member of murine hepatitis viruses (MHVs). The nucleotide sequences of the genes encoding the hemagglutinin-esterase (HE) and the spike (S) glycoproteins from DVIM were determined and compared with those of other MHVs. The deduced amino acid sequence of the HE protein was most similar to that of MHV-S strain (94% identity), and the S protein sequence was most similar to that of MHV-Y strain (90% identity). The DVIM HE protein has a unique N-linked glycosylation site in addition to other glycosylation sites common to many MHV strains. Unlike in some typical MHV strain, such as MHV-A59 and MHV-JHM, the vast majority of the S glycoprotein molecules in DVIM exist an uncleaved form probably due to several amino acid substitutions around the cleavage site.
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A particular T cell population expressing NK cell markers, CD56 and CD57, exists in humans. Many CD56+ T and CD57+ T cells (i.e. NK T cells) exist in the liver and increase in number in the blood with ageing. They may be a human counterpart of extrathymic T cells, similar to NK1.1+ CD3int cells seen in mice. We investigate here the existence of such NK T cells in human cord blood and the in vitro expansion of these cells by the stimulation of human recombinant IL-2 (rIL-2). There were very small populations (< 1.0%) of CD56+ T cells, CD57+ T cells, and gamma delta T cells in cord blood. However, all of these populations increased in number after birth and with ageing. When lymphocytes in cord blood were cultured with rIL-2 (100 U/ml) for 14 days, CD56+ T cells expanded up to 25% of T cells. CD57+ T cells were never expanded by these in vitro cultures. The expansion of gamma delta T cells (mainly V gamma9- nonadult type) also occurred in the in vitro culture. A considerable proportion of CD56+ T cells was found to use V alpha24 (i.e. equivalent to invariant V alpha14 chain used by murine NK T cells) for TCR alpha beta. These results suggest that neonatal blood contains only a few NK T cells but CD56+ NK T cells and gamma delta T cells are able to expand in vitro.
AIMS: Recent reports suggest that genetic examination of K-ras or p53 mutation is more sensitive for the detection of occult lymph node metastasis in colorectal carcinomas than conventional examination by haematoxylin and eosin (H & E) staining or immunohistochemistry for gene products. The aim of this study was, first, to define the microscopic characteristics of metastatic cancer cells in lymph nodes stained by the anti-cytokeratin antibody CAM5.2 for cytokeratins 8 and 18, and, second, to compare the detection rate of occult lymph node metastasis for immunohistochemical vs genetic methods. METHODS AND RESULTS: K-ras mutations were first examined in primary tumours of seven cases which showed distant metastasis or local recurrence within 5 years of the initial surgery in spite of the original reporting of no lymph node metastasis by routine H & E staining. K-ras mutations were positive in three cases in primary tumours and lymph nodes, and the remaining four primary tumours were negative for p53 mutation as well as K-ras mutation. Therefore, genetic analysis of occult lymph node metastasis was uninformative, but occult metastasis was detected by cytokeratin staining in two of these four cases. Comparative study of cytokeratin-positive cells was performed on each of the 43 lymph nodes from three cases with K-ras mutations. Cancer cells were detected in 28 of the 43 lymph nodes (65.1%) by cytokeratin staining and in 10 of the 43 corresponding lymph nodes (23.3%) by genetic analysis. Artefactual contamination by cancer cells was present in eight of the 28 cytokeratin positive lymph nodes, and three of the eight nodes were genetically positive. CONCLUSIONS: This study suggests that cytokeratin immunohistochemistry is more sensitive and specific for the detection of occult lymph node metastasis than genetic diagnosis by K-ras mutation in cases with genetic alterations as well as in cases without them.
MRL-lpr/lpr (lpr) mice fall victim to autoimmune disease owing to a lymphoproliferative disorder mainly of double-negative (DN) CD4- CD8- alpha beta T cells expressing a low density of interleukin-2 receptor beta-chain (IL-2R beta). It was previously revealed that the lpr gene is a defective Fas gene, into which an early transposon (ETn) of retrovirus is transfected. As a result of the failure of apoptosis, intermediate T-cell receptor (TCR) cells (i.e. TCRint cells) with DN phenotype abnormally accumulate in the periphery of lpr mice. We investigated herein how these TCRint cells are selected in terms of CD4, CD8 and TCR in lpr mice. When a whole fraction of mononuclear cells (MNC) in various immune organs of lpr mice was injected into scid mice (allogeneic circumstance), CD8+ TCRint cells mainly expanded. They had a high density of IL-2R beta. This was true when bone marrow cells of lpr mice were injected into scid mice. On the other hand, when MNC of the spleen and bone marrow in lpr mice were injected into irradiated (9 Gy) lpr mice (syngeneic circumstance), the major expanding cells were DN TCRint cells expressing a low density of IL-2R beta. A cell-sorting experiment for purified fractions demonstrated that only CD8- cells reconstituted TCRint cells in scid mice. Namely, DN CD4- CD8- cells as well as CD4+ cells which once acquired the mature phenotype, no longer switched their phenotype. These results suggest that the phenotype of TCRint cells is influenced by the surrounding microenvironment.
In Brassica species that exhibit self-incompatibility, two genes, SLG and SRK, at the S locus are involved in the recognition reaction with self and non-self pollen. From a pollen-recessive S29 haplotype of Brassica rapa, both cDNA and genomic DNA clones for these two genes were isolated and characterized. The nucleotide sequence for the S domain of SRK29 showed a high degree of similarity with that of SLG29, and they belong to Class II type. RNA gel blot analysis showed that the transcript of SLG29 consisted of the first and second exons, and no other transcript containing any part of the intron sequence was detected. Because no transmembrane domain was encoded by the second exon of SLG29, SLG29 was designated a secreted type glycoprotein. SLGs of two other pollen-recessive haplotypes, S40 and S44, of B. rapa also had a similar structure to that of SLG29. Previously, SLG2 from a pollen-recessive haplotype, S2, of Brassica oleracea was found to produce two different transcripts, one for the secreted type glycoprotein and the other for a putative membrane-anchored form of SLG. Therefore, the nature of these SLGs from pollen-recessive haplotypes of B. rapa is different from that of SLG2 of B. oleracea.
When C57BL/6 (B6) mice were irradiated (9 Gy) and received bone marrow (BM) cells of B6-lpr/lpr mouse origin (i.e., lpr-->B6), all mice died within 6 days. In the irradiated B6 mice, radioresistant CD3 IL-2Rbeta+ NK cells and IL-2Rbeta+ CD3int cells (i.e., CD3int cells of extrathymic origin) remained, especially in the liver. There were two subsets, NK1.1+ and NK1.1-, among the IL-2Rbeta+ CD3int cells. However, the NK1.1+ subset (i.e., NK1.1- T cells) was much more radioresistant, and the majority of CD3int cells belonged to this subset in irradiated mice. The expansion of lymphocytes from injected BM cells did not occur in the irradiated B6 mice. However, such expansion did take place in irradiated B6-lpr/lpr mice injected with both BM cells of B6-lpr/lpr and B6 origin. As a result, the mice subjected to BM cells survived. Irradiated B6 mice were treated in vivo with anti-NK1.1 mAb or anti-asialoGM1 antibody to eliminate NK cells alone or both NK cells and NK1.1+ T cells. When irradiated B6 mice were pretreated with anti-NK1.1 mAb, the mice could survive. These results suggest that intact NK1.1+ T cells of extrathymic origin may recognize abnormal BM cells with the lpr gene and inhibit the expansion of lymphocytes, including abnormal double-negative CD4 8 cells, in B6-lpr/lpr mice. To inhibit the expansion of lymphocytes, mechanisms other than Fas ligand/Fas molecules on extrathymic T cells may be responsible.
The aim of this study was to clarify whether or not the status of gene alteration is heterogeneous in intramucosal carcinoma and homogeneous within invasive carcinoma. We selected 10 colorectal carcinoma cases (1 mucosal, 5 submucosal and 4 advanced carcinomas including 2 cases with lymph node metastasis) and analyzed the p53 gene sequence. Six colorectal cancers in this study showed heterogeneity in p53 mutations in cells from the intramucosal part. In the invasive part of a carcinoma, p53 mutation status was homogeneous intratumorally in all cases. These data indicate that, in regard to p53 gene alterations, colorectal cancers can be composed of various subclones when limited to the mucosa, but clonal selection occurs when one of these subclones commences invasion to the submucosa, generating a monoclonal invasive carcinoma.
In esophageal squamous cell carcinoma, p53 gene mutations have been analyzed for inter- or intra-patient heterogeneity but only a few studies have investigated intratumoral heterogeneity. We investigated this question within individual esophageal cancers, and also in their lymph-node metastases in 8 cases. Analyzing the p53 gene sequence by direct sequencing of polymerase chain reaction products, we found heterogeneity for p53 mutations in the pre-invasive area in 3 esophageal cancers. In all areas sampled in the invasive portion of each cancer, the p53 mutational status was identical in a given tumor. In heterogeneous tumors, the invasive area showed one of the p53 mutations found in the pre-invasive area. In nodal metastases, the p53 mutation was identical to that in the invasive area of each primary tumor. These data suggest that the timing of p53 alteration is not as early as might have been expected, indicating that, in regard to p53 gene alteration, some esophageal cancers are composed of various subclones in the pre-invasive stage with invasiveness developing in one of them, which becomes predominant through clonal selection.
A case of malignant fibrous histiocytoma metastases to the small intestine and colon presenting as an intussusception is described. Although malignant fibrous histiocytoma is the most common soft tissue sarcoma in late adult life, GI involvement has rarely been reported. The review of both our case and eight cases in the English-language literature suggests that GI involvement from malignant fibrous histiocytoma occurs most frequently in the small intestine (six of nine) and that two major clinical manifestations of GI involvement are GI bleeding (five of nine) from ulcerated tumors and intussusception (two of nine) led by polypoid tumors.
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Under continuous ECG and oxygen saturation (SpO2) monitoring, the following measurements were taken by Doppler echocardiography in 6 consecutive patients with tetralogy of Fallot (TF) before and after intravenous administration of disopyramide (2mg/kg): left ventricular shortening fraction (LVSF); peak velocities in the right ventricular outflow tract (RVOT); diastolic and systolic internal diameters of the right ventricular outflow tract (dRVOT, sRVOT); and systolic blood pressure. SpO2 increased (p<0.01) from 78 to 98 (89 +/- 7, mean +/- standard deviation)% to 86-99 (94 +/- 5)%. LVSF decreased (p<0.05) from 0.34-0.56 (0.42 +/- 0.08) to 0.22-0.54 (0.33 +/- 0.13). The systolic blood pressure fell slightly (p<0.05) from 68-92 (79 +/- 8) to 64-92 (71 +/- 11)mmHg. The sRVOT increased (p<0.05) from 2.1-4.8 (2.7 +/- 1.5)mm to 3.0-8.1 (4.9 +/- 2.4)mm, while RVOT peak velocity decreased (p<0.05) from 2.20-4.88 (3.70 +/- 0.97)m/sec to 2.05-4.07 (2.92 +/- 0.72)m/sec. Disopyramide alleviates hypoxia in patients of TF through its negative inotropic action on right ventricular outflow obstruction.
The aim of this study was to investigate whether distensibility of the persistent ductus arteriosus (PDA) might predict its potential for vasoconstriction. Epinephrine-induced constriction and stretching were investigated in 10 patients with PDA. Age, sex, ductus type, its minimal diameter, its stretched minimal diameter, and its stretch index were compared between epinephrine responders and non-responders. Age, sex, weight or the configuration or size of the PDA did not predict stretchability. The stretch index was significantly greater in responders (1.7-2.0, 1.8+/-0.1) than in non-responders (1.3-1.7, 1.4+/-0.2, p<0.01). Stretching of the PDA may depend on the elasticity of the vascular wall, which in turn is determined by preservation of vascular smooth muscle.
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