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Biomedical subjects

H Saeki

Publications and source records attributed to H Saeki.

At least 55 records · Page 3Linked to original sources

p53 polymorphism in human papillomavirus-associated esophageal cancer.

Human papillomavirus type 16/18 (HPV-16/18) is implicated in the pathogenesis of squamous cell carcinoma (SCC) of the cervix and esophagus. The arginine allele at codon 72 of p53 was found to be more susceptible to degradation by HPV E6 protein than is the proline allele in vivo, thus resulting in a high frequency of cervical SCC in individuals homozygous for arginine at the codon. There are controversial results from several clinical studies of cervical SCC. In the present study, encoding regions of p53 codon 72 and HPV-16/18 E6 were directly sequenced, using pairs of primary esophageal SCC tissue and corresponding normal mucosa, which were from 75 patients (Japanese, n = 38; Chinese, n = 37). The arginine allele alone was detected in 70.6% (12 of 17) of HPV-positive cases but only in 43.1% (25 of 58) of HPV-negative cases (P < 0.05). In contrast, such a significant correlation between p53 polymorphism and HPV infection was not evident in corresponding normal mucosae. Because our findings between tumor specimens and the normal mucosae differed, we suggest that the frequent loss of proline allele in HPV-associated carcinogenesis of the esophagus major plays some role. The particular type of p53 polymorphism may indicate a potential candidate for HPV-associated SCC.

Alleles↗

Major complications during spasm provocation tests with an intracoronary injection of acetylcholine.

This study sought to clarify major complications associated with acetylcholine testing. Serious major complications, such as sustained ventricular tachycardia, shock, and cardiac tamponade were determined in 4 of 715 patients (0.56%), but no cases of death or irreversible complications occurred. The spasm provocation test using acetylcholine should be performed carefully, although it is considered a safe and reliable method.

Acetylcholine↗

Grb7 signal transduction protein mediates metastatic progression of esophageal carcinoma.

We have previously reported the association of tumor cell invasion with expression of growth factor receptor-bound protein 7 (Grb7). This molecule contains a Src homology 2 (SH2) domain and shares structural homology with a cell migration molecule designated Mig-10 found in Caenorhabditis elegans. In the present study, Grb7 expression was analyzed in human esophageal carcinomas with or without metastatic spread. The Grb7 protein was overexpressed in 14 of 31 esophageal carcinomas as compared to the adjacent normal mucosa (45%) and this finding was significantly correlated with the presence of lymph node metastases. We also identified that Grb7 protein in esophageal carcinoma cells was phosphorylated on tyrosine by epidermal growth factor as well as attachment to extracellular matrix proteins including fibronectin. Such fibronectin-dependent phosphorylation of Grb7 was regulated by integrin signaling that leads to the interaction with focal adhesion kinase protein. Furthermore, ectopic expression of a Grb7-SH2 dominant-negative fragment inhibited the fibronectin-dependent phosphorylation of endogenous Grb7, and reduced migration of esophageal carcinoma cells into fibronectin. Our results suggest a role of Grb7 mediated signal transduction in generation of an invasive cell phenotype against extracellular matrix, and thus contributes to metastatic progression of human esophageal carcinoma.

Adenocarcinoma↗

A migratory population of skin-derived dendritic cells expresses CXCR5, responds to B lymphocyte chemoattractant in vitro, and co-localizes to B cell zones in lymph nodes in vivo.

Chemokine receptors on dendritic cells (DC) and chemokines within lymph nodes (LN) contribute to trafficking of DC to appropriate sites within the LN. Here we show that DC that have migrated out of skin ex vivo (migratory DC, migDC) express 50-fold more CXCR5 mRNA than fresh Langerhans cells and migrate in response to B lymphocyte chemoattractant (BLC) in vitro. When injected into the footpad of mice, migDC emigrate to regional LN where up to 40% are found in B cell zones. By contrast, murine bone marrow-derived DC display 14-fold less CXCR5, do not migrate to BLC in vitro, and migrate strictly to T cell zones in LN. We propose that activated skin DC utilize CXCR5 and BLC as a possible mechanism to home to B cell zones of LN, where they may have direct effects on B cells.

Animals↗

Current status of cancer patients' perception of alternative medicine in Japan. A preliminary cross-sectional survey.

Since there are no large-scale surveys of how cancer patients perceive unproven therapy in Japan, we wanted to clarify this issue by means of a cross-sectional questionnaire conducted among cancer patients. The survey revealed that 32% of cancer patients used unproven therapy without having sufficient information about it. There was a lack of communication between cancer patients and their physicians on topics relating to alternative medicine. Issues that we have to solve are concerned with the education of cancer patients, lay people and physicians on the meaning and role of alternative medicine and on the necessity for scientific evaluation of medical treatments in Japan.

Complementary Therapies↗

Pulmonary function after lobectomy: video-assisted thoracic surgery versus thoracotomy.

BACKGROUND: Whether video-assisted thoracic surgery (VATS) improves postoperative pulmonary function is still controversial. We compared postoperative pulmonary function after VATS lobectomy and standard lobectomy. METHODS: Eleven patients who had undergone standard lobectomy and 10 patients who had undergone VATS lobectomy were studied. Arterial blood gas analyses were performed on the 4th, 7th, and 14th postoperative days. Pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1.0), and peak flow rate (PFR) were measured on the 7th and 14th postoperative days (early phase), and approximately 1 year after surgery (late phase). RESULTS: Pulmonary function, as assessed with arterial oxygen partial pressure (PaO2) (p = 0.054), arterial oxygen saturation (O2SAT) (p = 0.063), FVC (p = 0.10), and FEV1.0 (p = 0.08), was better after VATS lobectomy than after thoracotomy on the 7th postoperative day. PFR was significantly better after VATS on both the 7th and 14th postoperative days (p = 0.008 and p = 0.03, respectively). CONCLUSIONS: VATS lobectomy had advantages on early postoperative pulmonary function. We conclude that VATS lobectomy is a beneficial alternative to standard thoracotomy, especially for patients with poor pulmonary reserve.

Aged↗

Preparation of neoglycoprotein from carp myofibrillar protein and alginate oligosaccharide: improved solubility in low ionic strength medium.

Alginate oligosaccharide (AO) was conjugated with carp myofibrillar protein (Mf) by using the controlled Maillard reaction, and the change in the solubility of Mf in low ionic strength media as affected by the glycosylation was investigated. AO was prepared by degrading sodium alginate using alginate lyase, which was purified from the culture supernatant of Pseudoalteromonas elyakovii. When a lyophilized Mf and AO mixture was incubated at 40 degrees C and 65% relative humidity, the conjugation of AO was confirmed at myosin heavy chain, actin, and tropomyosin. When >30 microg/mg of AO was conjugated to Mf, the protein solubility in a low ionic strength medium was greatly improved without significant loss of available lysine. These results indicate that the conjugation with AO is a superior manner for improving the water solubility of Mf in view of its nutritional aspect.

Alginates↗

Alcohol consumption and cigarette smoking in relation to high frequency of p53 protein accumulation in oesophageal squamous cell carcinoma in the Japanese.

We investigated levels of p53 protein expression in Japanese patients with oesophageal squamous cell carcinoma. A significantly larger proportion of heavy alcohol drinkers and cigarette smokers was evident in the p53-positive group. The combination of drinking and smoking was associated with a high frequency of p53 protein accumulation.

Alcohol Drinking↗

Prognostic factors in patients with submucosal carcinoma of the oesophagus.

To clarify the prognostic factors in patients with submucosal carcinoma of the oesophagus, we examined the results of surgical treatment for 78 cases over the last decade. The clinicopathological factors including age, sex, location of the tumour, length of the tumour, histological differentiation, subclassification of depth, lymphatic or blood vessel invasion, intramural metastasis and lymph node metastasis were all analysed. Then the correlation between these factors and prognosis was investigated. As a result, significant differences were observed in the survival rates between the groups regarding lymphatic vessel invasion (P = 0.0003), intramural metastasis (P = 0.0051) and lymph node metastasis (P = 0.0026). According to a multivariate analysis, intramural metastasis (P = 0.0038, relative risk 9.17), vessel invasion (P = 0.0033, relative risk 6.25) and lymph node metastasis (P = 0.0187, relative risk 3.62) were found to be independent prognostic factors. The prognosis of the patients with at least one of these factors was significantly poorer than that without. The five-year survival rate of the patients without these factors was as good as that with mucosal carcinoma of the oesophagus. Based on our findings, vessel invasion, intramural metastasis and lymph node metastasis are thus considered to be significant prognostic factors in patients with submucosal carcinoma of the oesophagus.

Age Factors↗

Effects of presurgical local infiltration of bupivacaine in the surgical field on postsurgical wound pain in laparoscopic gynecologic examinations: a possible preemptive analgesic effect.

OBJECTIVE: A randomized, double-blind, controlled study was designed to evaluate the effect of presurgical local infiltration of bupivacaine in the surgical field on postsurgical wound pain relief and analgesic requirements in 28 healthy patients scheduled for laparoscopic gynecologic examinations. INTERVENTIONS: After induction of general anesthesia by routine methods, the patients were randomly divided into two groups. In the bupivacaine (B) group (n = 15), patients were injected with 5 ml of 0.25% bupivacaine at each incisional area (four sites, total of 20 ml) approximately 15 minutes before skin incision. In the control (C) group (n = 13), the surgical field was injected with an equal volume of physiologic saline solution (four sites, total of 20 ml). OUTCOME MEASURES: Postsurgical wound pain at rest was evaluated by a 10-cm visual analog pain scale at 1, 10, 24, and 72 hours and 1 month after surgery. The patients were interviewed via telephone 1 month after hospital discharge for re-evaluation of resting pain. RESULTS: The results indicated that the incidence of postsurgical wound pain for up to 10 hours after surgery in group B was significantly lower (p < 0.05) than in group C. Pain intensity ranged from mild to moderate (2-5 cm). In addition, the mean visual analog pain scale pain intensity was significantly less for group B (0.31 +/- 0.85 cm) than for group C (2.62 +/- 2.06 cm) for up to 10 hours after surgery (p < 0.05). The number of patients who requested analgesics and complained of sleep disturbances was significantly higher in group C (p < 0.05). The mean cumulative dose of diclofenac sodium at 24 hours was significantly (p < 0.05) lower in group B (6.67 +/- 17.6 mg) than in group C (30.8 +/- 25.3 mg). Prolonged postsurgical wound pain persisting 1 month after surgery was observed in one patient in group C. CONCLUSIONS: It is concluded that presurgical infiltration of 0.25% bupivacaine in the surgical field is a useful method for decreasing postsurgical wound pain for up to 10 hours and analgesic consumption for up to 24 hours after laparoscopic gynecologic examination.

Adult↗

Two cases of atypical carcinoid of the thymus.

We describe two cases of atypical carcinoid of the thymus. One was an 82-year-old woman with complaints of nonproductive cough and back pain, and the other a 64-year-old woman with no symptoms. Computed tomography scans of the chest in both cases revealed a large mass in the anterior mediastinum. Multiple metastases to bone and liver were also noted in the former case. Histological examination of their tumors revealed that the tumor cells were arranged in a nested, trabecular, or pseudorosette pattern, with increased numbers of mitoses, nuclear pleomorphism, and presence of necrosis. In addition, immunohistochemically, the cells stained for neuron-specific enolase, synaptophysin and chromogranin A. Combination chemotherapy consisting of carboplatin and etoposide was performed as initial chemotherapy in the former case and as adjuvant therapy in the latter. The former patient achieved a short-term partial response. It is important to differentiate atypical carcinoid from other thymic tumors, since such tumors including thymoma have a much better prognosis than does atypical carcinoid.

Aged↗

[Changes in the antibacterial activity of chemotherapeutic agents (especially carbapenems) for 10 species of clinical isolates between 1994 and 1996. Surveillance group of the sensitivities of clinical isolates to antibacterial agents].

During October and December of each year of from 1994 to 1996, 3,849 strains of 10 species of bacteria were isolated from clinical materials in 21 institutions nationwide. The minimum inhibitory concentrations (MICs) for these bacteria of four carbapenems (imipenem [IPM], panipenem [PAPM], meropenem [MEPM], and biapenem [BIPM]) and other representative antibacterial agents were measured to investigate annual changes in antibacterial activity. Carbapenems showed potent activity against methicillin-sensitive S. aureus (MSSA), S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, S. marcescens, and the B. fragilis group, with the activity being stable. However, these drugs showed weak activity against methicillin-resistant S. aureus (MRSA) and P. aeruginosa. The antibacterial activity (MIC90) against the tested organisms generally remained stable. Particularly, there was annual improvement of the MIC90 values of IPM and BIPM for S. pneumoniae, as well as the values of IPM and PAPM for H. influenzae, and those of IPM, PAPM, and BIPM for S. marcescens. On the other hand, the activity of carbapenems (including IPM) against MRSA was not necessarily strong, but there was annual improvement of MIC90 values.

Bacteria↗

Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes.

Dendritic cells (DCs) emigrate to regional lymph nodes (LNs) during immune responses via afferent lymphatic channels. Secondary lymphoid-tissue chemokine (SLC), a CC chemokine, is expressed in secondary lymphoid organs and mediates the chemotaxis of lymphocytes and DCs via its receptor, CC chemokine receptor 7 (CCR7). By dual-label fluorescence confocal microscopy, we showed MHC class II-positive cells within SLC-staining lymphatic channels in the mouse dermis. SLC was a potent in vitro chemoattractant for cultured, migratory skin DCs, and it enhanced the emigration of MHC class II-positive DCs from mouse skin explants by an average of 2.5-fold. Mature or cytokine-activated, but not resting, Langerhans cells expressed CCR7 mRNA by RT-PCR. Anti-SLC Abs, but not control or anti-eotaxin Abs, blocked the in vivo migration of 51Cr-labeled, skin-derived DCs from footpads to draining LNs by 50% (n = 9, p < 0. 005). Thus, we provide direct evidence that SLC and CCR7 participate in the emigration of DCs from peripheral tissue to LNs via lymphatics.

Animals↗

Fractalkine, a CX3C chemokine, is expressed by dendritic cells and is up-regulated upon dendritic cell maturation.

The lone CX3C chemokine, fractalkine (FK), is expressed in a membrane-bound form on activated endothelial cells and mediates attachment and firm adhesion of T cells, monocytes and NK cells. We now show that FK is associated with dendritic cells (DC) in epidermis and lymphoid organs. In normal human skin, dual-color fluorescence microscopy co-localized FK expression with Langerhans cells expressing CD1a. In tonsil, FK-positive DC expressed CD83, a marker for mature DC. Human and murine cultured DC up-regulated FK mRNA expression with maturation. Furthermore, CD40 ligation, but not TNF-alpha or lipopolysaccharide treatment, of activated, migratory DC that had migrated from skin explants resulted in a 2.5-fold increase of surface expression of FK without significant alterations of expression of CD80, CD86, CD54 or MHC class II. Since FK mediates adhesion of T cells to activated endothelial cells, the increased expression of FK during DC maturation (and particularly by CD40 ligation) may play a role in the ability of T cells and mature DC to form conjugates and engage in cell-cell communication.

Animals↗

Esophageal carcinoma showing a long stricture due to prominent lymphatic permeation: report of a case.

Some esophageal diseases such as carcinoma, esophagitis, and collagen diseases have often been reported to show a diffusely thickened esophageal wall in the roentogenogram findings. In the current report, a preoperative upper gastrointestinal series and an endoscopic examination showed a diffusely infiltrative type carcinoma, but other examinations did not suggest any diseases such as esophagitis or collagen diseases which might cause a thickening of the esophageal wall or a constriction of the esophagus. A postoperative histological examination revealed the primary carcinoma to remain only within the mucosal layer, while a large degree of lymphatic vessel permeation reached the adventitia over a wide area. An extraordinary degree of lymphatic permeation spread through the esophageal wall, and stromal fibrosis developed as a result of such lymphatic permeation. These histological phenomena might thus have led to the macroscopic appearance of infiltrative type esophageal carcinoma.

Carcinoma, Squamous Cell↗

Clinical investigation of atypical adenomatous hyperplasia of the lung.

The clinicopathologic characteristics of atypical adenomatous hyperplasia (AAH) remain unclear. A total of 137 patients underwent resection for adenocarcinoma of the lung at our institution. Examination of resected lung tissue showed that in addition to adenocarcinoma AAH was present in 26 cases and was not present in 111 cases. All nonsmokers with AAH (n = 13) had earlier-stage disease (stage IA, IB, IIA, and IIB) and no history of respiratory disease. Among patients with stage IA disease, the relapse-free and overall survival curves for those with AAH (n = 14) tended to be better than for those without AAH (n = 40), but the difference was not statistically significant (P = 0.056 and 0.087, respectively). Concurrent presence of AAH may be a favorable prognostic indicator in patients with stage IA adenocarcinoma.

Adenocarcinoma↗