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Biomedical subjects

T Tsuji

Publications and source records attributed to T Tsuji.

At least 73 records · Page 4Linked to original sources

The formation of capsule and septum in human hepatocellular carcinoma.

The formation of fibrous capsule around the cancer nodule and of the septum in the tumor is frequently observed with the development of hepatocellular carcinoma (HCC). We aimed to clarify how the capsule and septum were formed during the growth of HCC. Liver samples surgically resected from 25 patients with HCC were studied with in situ hybridization for type-I, -III, and -IV procollagen. Type-I and -III procollagen-expressing cells, mostly alpha-smooth muscle actin (SMA)-positive, were increased in the fibrous capsule and in the septum between HCC nodules. These cells were also found at the invasion front of HCC and around the necrotic cancer tissues. Type-IV procollagen gene expression was mainly observed in mesenchymal cells localized in both HCCs and non-cancerous liver. Cancer cells or hepatocytes did not express any of these procollagen genes. The present study reveals that the capsule and septum are mainly formed by alpha-SMA-positive mesenchymal cells at the interface between two different tissues (e.g., cancer nodule vs non-cancerous liver or another cancer nodule). The wound healing occurs even in HCC. The capsule formation may result from interaction between tumor and host liver and interfere the growth and invasion of HCC.

Actins↗

Circulating sialyl Lewis(x), sialyl Lewis(a), and sialyl Tn antigens in colorectal cancer patients: multivariate analysis of predictive factors for serum antigen levels.

Preoperative serum levels of sialyl Lewis(a) (CA 19-9), sialyl Lewis(x) (SLX), and sialyl Tn (STN) antigens in colorectal cancer patients were examined to establish predictive factors for serum levels of these antigens compared with carcinoembryonic antigen (CEA). A total of 308 patients who underwent resection for a colorectal cancer were divided into low and high antigen groups (higher or lower than a selected diagnostic-based cutoff value). The cutoff values were 37 U/ml for CA19-9, 38 U/ml for SLX, 45 U/ml for STN, and 2.5 ng/ml for CEA. The American Joint Committee on Cancer Classification and Stage grouping was used to classify the tumors. Statistical tests were conducted using univariate and multivariate logistic regression analyses. For CA19-9, 81 patients (26.3%) were assigned to the high antigen group: for SLX, 39 (12.7%); for STN, 33 (10.7%); and for CEA, 133 (43.2%). Multivariate logistic regression analysis revealed that predictive factors associated with high antigen levels were female sex (odds ratio [OR], 1.78 vs male sex), T4 (OR, 3.26 vs T1/T2), and M1 (OR, 3.35 vs M0) for CA19-9; M1 (OR, 6.40 vs M0) for SLX; mucinous carcinoma (OR, 8.45 vs well differentiated adenocarcinoma) and M1 (OR, 8.24 vs M0) for STN; and mucinous carcinoma (OR, 7.21 vs well differentiated adenocarcinoma), T3/T4 (OR, 3.84/4.18, respectively, vs T1/T2), and M1 (OR, 6.39 vs M0) for CEA. In conclusion, high serum levels of CA19-9, SLX, and STN are strongly associated with distant metastasis. In addition, high serum levels of CA19-9 may be an independent predictor for female gender and T4, and high serum levels of STN may be an independent predictor for mucinous carcinoma.

Aged↗

Minilaparotomy wound edge protector (Lap-Protector): a new device.

Laparoscopic-assisted or minimally invasive surgery involving minilaparotomy is occasionally complicated by infection of the minilaparotomy wound caused by intestinal bacteria. Furthermore, when this procedure is performed to excise colorectal or gastric cancer, tumor recurrence may develop in the minilaparotomy wound. In an attempt to minimize the risk of these complications, we developed a new, easy-to-use device which we named the "Lap-Protector." Minilaparotomy was performed using the Lap-Protector in 28 patients with colon cancer and eight patients with early gastric cancer who underwent minimally invasive surgery between January and September, 1999. During a median follow-up period of 15.9 (range 12.4-21.0) months, none of the 36 patients showed any sign of wound infection or tumor recurrence in the minilaparotomy wound. These results indicated that the Lap-Protector is a safe and useful device that may help to prevent infections and cancer cell contamination of the minilaparotomy wound.

Aged↗

Surgical treatment and subsequent outcome of patients with carcinoma of the splenic flexure.

Extended resection, comprising extended right hemicolectomy, splenectomy, and distal pancreatectomy, has been advocated for carcinoma of the splenic flexure because the lymphatic drainage at this site is variable. The present study addresses the problems associated with selecting the most appropriate operative procedure to achieve cure of splenic flexure cancers. We conducted a retrospective review of 27 patients with splenic flexure cancer who underwent curative resection. Left partial colectomy was performed in 20 patients and partial resection of the transverse/descending colon was performed in 7 patients. The combined resection of adjacent organs due to tumor adherence was performed in three patients. The spleen and distal pancreas were the organs most frequently resected among a collective total of six adjacent organs. The median duration of follow-up was 60.9 months after resection for splenic flexure cancer. No patient developed local recurrence. There was no significant difference in 5-year survival between patients with splenic flexure cancers and those with colon cancers at other sites. In conclusion, splenic flexure cancer resected by left partial colectomy or partial resection of the transverse/descending colon without routine extended resection was not associated with a worse prognosis than colon cancers at other sites.

Adenocarcinoma↗

Distribution of bone mineral density in the proximal tibia in mid-teens.

The distribution of bone mineral density (BMD) in the proximal tibia was studied in 94 knees from 47 mid-teens. The subjects were healthy high school freshmen (19 male; 28 female) who engaged in daily physical exercise. We measured BMD at six regions of interest (ROI) at the bilateral proximal tibia (three immediately above and three immediately be-low the physeal line) using dual-energy X-ray absorptiometry (QDR-2000; Hologic, Waltham, MA, USA). Subjects were supine during the measurements, with the knee extended and the foot fixed in a special holding device, ensuring correct rotational alignment of the knee. Measurements were performed using the forearm array scan mode. The precision of this method (coefficient of variation) was 1.1%-4.9% (mean 2.5%) for six ROIs. The BMD of the medial side was higher than that of the lateral side, and the BMD at the center of the metaphysis was higher than that of the epiphysis. The subjects in the present study did not show any misalignment of the knee joints. These findings indicate that the medial side of the proximal tibia already has higher BMD than the lateral side in teenagers with normal alignment of the knee joint, and that the increase in epiphyseal BMD may be slower than that of metaphyseal BMD. It is suggested that this phenomenon should be life-long and may play a role in the progression of osteoarthritis of the knee.

Adolescent↗

Epidemiology of low back pain in the elderly: correlation with lumbar lordosis.

We carried out an epidemiologic study to determine the prevalence of low back pain in elderly Japanese and to examine the correlation with lumbar lordosis in sagittal plane radiographs. Low back pain is an enormous clinical and public health problem. With the increasing use of spinal instrumentation, the measurement of lumbar lordosis is thought to be important. However, in elderly Japanese, the prevalence of low back pain and its correlation with lumbar lordosis is not clear. Five hundred and nine people, aged 50-85 years, were examined, and 489 subjects met our criteria. Clinical findings, physical status, and the visual analogue scale (VAS) of pain were examined in these subjects. Measurements and determination of total lordosis from L1-S1 were made from standing radiographs. Forty-eight percent of the subjects had experienced low back pain within the previous 3 months. Women had low back pain more frequently (P = 0.006). There was a significant difference in lumbar lordosis between the groups with and without low back pain (P = 0.0006). Lumbar lordosis was approximately 4 degrees less in the low back pain group and there was no relationship to age or sex in either group. VAS was significantly inversely correlated with lumbar lordosis (P = 0.025, at rest). The body mass index (BMI) of the low back pain group was higher in women, but the difference was not significant (P = 0.06). In conclusion, lumbar lordosis was defined and its prevalence in elderly Japanese was reported together with VAS and physical data used to compare the two groups.

Aged↗

Colectomy for colon cancer via a 7-cm minilaparotomy.

We herein describe our technique for performing a colectomy to resect colon cancer via a 7-cm minilaparotomy using conventional surgical techniques and instruments. By moving the minilaparotomy wound laterally as well as either caudad or cephalad, the mobilization of the relevant segment of the bowel loop was thus made possible. To ensure an adequate visualization of the operative field during a dissection of the lymph nodes, an Omni-Tract retractor system was used. The division of the colonic mesentery, transection of the affected bowel, and bowel anastomosis were performed extracorporeally or at the level of the incision. This same operation was successfully performed in 102 patients with colon cancer. We conclude that a colectomy for colon cancer via a 7-cm minilaparotomy is an attractive alternative to a conventional full laparotomy in selected patients.

Colectomy↗

Adrenomedullin (11-26): a novel endogenous hypertensive peptide isolated from bovine adrenal medulla.

Adrenomedullin (AM) is a potent hypotensive peptide originally isolated from pheochromocytoma tissue. Both the ring structure and the C-terminal amide structure of AM are essential for its hypotensive activity. We have developed an RIA which recognizes the ring structure of human AM. Using this RIA, we have characterized the molecular form of AM in bovine adrenal medulla. Gel filtration chromatography revealed that three major peaks of immunoreactive AM existed in the adrenal medulla. The peptide corresponding to Mr 1500 Da was further purified to homogeneity. The peptide was determined to be AM (11-26) which has one intramolecular disulfide bond. Amino acid sequences of bovine AM and its precursor were deduced from the analyses of cDNA encoding bovine AM precursor. The synthetic AM (11-26) produced dose-dependent strong pressor responses in unanesthetized rats in vivo. The hypertensive activity lasted about one minute, and a dose dependent increase in heart rate was also observed. The present data indicate that AM (11-26) is a major component of immunoreactive AM in bovine adrenal medulla and shows pressor activity.

Adrenal Medulla↗

Ultrasonographic assessment of coronary flow reserve and abdominal fat in obesity.

Recent technological advances in transthoracic Doppler echocardiography (TTDE) have provided noninvasive measurement of coronary flow velocity reserve (CFVR). We aimed to quantitate a correlation between endothelial dysfunction and fat distribution. In 36 patients with obesity, 16 with noninsulin-dependent diabetes mellitus (DM) and 12 healthy volunteers, coronary flow velocity was measured at the distal site of the left anterior descending branch. CFVR was defined as the ratio of hyperemic (IV infusion of 0.15 mg/kg/min adenosine) to basal peak diastolic flow velocity. Abdominal wall fat index (AWFI) was estimated by ultrasonography. Insulin resistance was quantified by the euglycemic hyperinsulinemic clump method. AWFI was significantly related to CFVR (r = -0.46, p = 0.011) and insulin resistance (r = -0.71, p < 0.0001). CFVR could be noninvasively evaluated using TTDE. Coronary endothelial dysfunction indicated as CFVR, body fat distribution and insulin resistance was quantitatively correlated in obesity.

Abdomen↗

Skin premature aging induced by tobacco smoking: the objective evidence of skin replica analysis.

Epidemiological studies have showed that heavy smoking causes premature skin aging. Using a silicone rubber replica combined with computerized image processing, an objective measurement of skin's topography, we investigated the association between wrinkle formation and tobacco smoking in this study. The replica analysis was used to study the changes in the surface furrows of the volar forearm in 63 volunteers. Results confirmed that the depth (Rz) and variance (Rv) of furrows were increased and lines of furrows (Rl) were decreased with age. The replica analytic results showed that Rz and Rv in subjects with a smoking history > or =35 pack-years were significantly higher than non-smokers (P<0.05). Rl in subjects with a smoking history were significantly lower than non-smokers (P<0.05). In addition, the present results gave a good correlation between the parameters from the computerized replica analysis with the clinical grading assessment of wrinkles, which further confirmed that skin replica technique is an objective and efficacious tool in evaluation of skin premature aging.

Aged↗

High prevalence of TT virus in human bile juice samples: importance of secretion through bile into feces.

TT virus (TTV) is much more prevalent than we once imagined. With the use of primers designed from the noncoding regions, a more than 90% rate of TTV infection in the general population by polymerase chain reaction (PCR) has been reported, showing that nonparenteral transmission must play an important role to its epidemiology. We considered that TTV may be secreted through bile juice into feces to establish nonparenteral infection. Paired bile juice and serum samples were obtained from 26 patients who were receiving bile drainage. Feces were also recovered after the drainage tube was removed. TTV DNA was detected from 22 patients in serum (84.6%), and they were all TTV DNA positive in bile juice. Most feces samples recovered from TTV-positive patients were also TTV DNA positive. Secretion of TTV into bile juice appears to be common, and this could play an important role to its transmission and its epidemiology.

Bile↗

Prognostic factors in hepatic metastases of colorectal carcinoma: immunohistochemical analysis of tumor biological factors.

The present study was designed to provide a systemic analysis of prognosis in 62 patients who underwent hepatic resection for colorectal liver metastasis. The analyzed factors included microvessel counts stained by CD34 and expression of two adhesion molecules, E-cadherin and CD44 variant exon 6-(v6) in these tumors. No significant factors related to recurrence were identified and only negative expression of CD44v6 tended to correlate with recurrence (P = 0.075). A short disease-free period to recurrence was noted in patients with high CEA levels (>10 ng/ml) and H2/3 classification. A short surgical margin, H2/3 classification, high microvessel counts (>60/field, x200), and negative expression of CD44v6 and E-cadherin tended to be associated with poor prognosis. A high microvessel count was the most significant prognostic factor by multivariate Cox proportional hazards regression model. Hepatic resection without tumor exposure and a careful follow-up in cases identified with poor prognostic factors are necessary.

Adult↗

T cell repertoire in primary biliary cirrhosis: a common T cell clone and repertoire change after treatment.

T cell repertoire was analyzed in three early-stage primary biliary cirrhosis (PBC) patients, using reverse transcription-polymerase chain reaction and single-strand conformation polymorphism. Multiple expanded clones were demonstrated in livers and peripheral blood lymphocytes (PBL) of all three patients. Comparison of the repertoire of different parts of the liver demonstrated the presence of common clones in various Vbeta families. Comparison of the repertoire between the liver and PBL demonstrated that both CD4 and CD8 T cell clones were expanded. Sequence analysis of complementarity determining region 3 of the expanded clones revealed that relatively conserved amino acids were utilized in each patient and that an identical CD4 T cell clone having Vbeta16 was present in all three patients. The number of expanded T cell clones in PBL decreased markedly after the treatment with prednisolone. These results suggest that common T cell clones may play a pathogenic role in PBC.

Anti-Inflammatory Agents↗

Discovery of a novel serine protease inhibitor utilizing a structure-based and experimental selection of fragments technique.

We report a set of strategies to develop novel ligands (Structure Based and Experimental Selection of Fragments: SbE-SF). First, a docking simulation utilizing DOCK3.5 is performed in order to screen the fragment database, which was generated with the in-house program FRAGMENT++ specifically for docking simulation purposes. Although the affinity of these small molecules (fragments) is expected to be low, the affinity of fragments selected by computation is assayed by experiment to determine which ones can be potent inhibitors. After determining such key fragments. additional fragments are attached to the key ones in order to increase the binding affinity,taking into account the binding modes predicted by computation. This method has been applied to a thrombin inhibitor study, resulting in the discovery of a novel inhibitor exhibiting pIC50 = 7.9.

Drug Design↗

Aberrant expression of cytokeratin 7 as a histological marker of progression in primary biliary cirrhosis.

AIM: We evaluated the aberrant expression of cytokeratin 7 (CK-7) in hepatocytes as a marker of cholestasis and progression in primary biliary cirrhosis (PBC). PATIENTS AND METHODS: The expression of CK-7 was studied by immunohistochemistry in 83 cases of PBC. This expression was compared with biochemical data, the deposition of copper-associated protein, and previous histological classifications. RESULTS: In normal liver, CK-7 was expressed exclusively in bile duct epithelial cells (BDE). In PBC, the expression was also observed in hepatocytes. The expression pattern was classified as follows: Grade 0, BDE as in normal; Grade 1, proliferated bile ductules; Grade 2, periportal hepatocytes in addition to proliferated bile ductules; Grade 3, intralobular hepatocytes; Grade 4, the majority of hepatocytes. The grades correlated with serum bilirubin levels but not with serum levels of biliary enzymes. A discrepancy between the CK-7 grading and Ludwig's classification was noted in cases with Stage 1 of the CK-7 grading who were considered Stage 2 or 3 in Ludwig's classification, suggesting that cholestasis and inflammatory activity might be independent events. CONCLUSIONS: These results suggest that the aberrant expression of CK-7 in hepatocytes may be a marker of chronic cholestasis and progression in PBC.

Alkaline Phosphatase↗

Skin aging induced by ultraviolet exposure and tobacco smoking: evidence from epidemiological and molecular studies.

BACKGROUND: Tobacco smoking, similar to ultraviolet (UV) A radiation exposure, has previously been identified as an important factor contributing to premature aging of human skin. OBJECTIVE AND DESIGN: To investigate the relationship between these two environmental factors, we have conducted a cross-sectional study of 83 subjects (48 males, 35 females, age range 23-95), in which sun exposure, pack-years of smoking history and potential confounding variables were assessed by questionnaire. Facial wrinkles were quantified using the Daniell score. In order to study the molecular mechanism by which smoking caused wrinkle formation, in vitro studies were conducted to assess the alteration of matrix metalloproteinase-1 (MMP-1) mRNA expression in human fibroblasts stimulated with tobacco smoke extract or/and UVA. RESULTS: Logistic statistic analysis of the data revealed that age [odds ratio (OR)=7.5, 95% confidence interval (CI)=1.87-30.161, pack-years (OR=5.8, 95% CI=1.72-19.87), and sun exposure (OR=2.65, 95% CI=1.0-7.0) independently contributed to facial wrinkle formation. When excessive sun exposure (>2 h/day) and heavy smoking (35 pack-years) occurred together, the risk for developing wrinkles was 11.4 times higher than that of non-smokers and those with less sun exposure (<2 h/day) at the same age. The in vitro studies revealed that MMP-1 expression was significantly increased in fibroblasts after the stimulation with either tobacco smoke extract or UVA. Maximum induction was observed when cells were treated with tobacco smoke extract plus UVA, indicating that the two factors act in an additive manner. MMP-1 induction was significantly higher in the low glutathione (GSH) content fibroblast compared to that in the high GSH fibroblast, indicating that the differences in glutathione content define the susceptibility of fibroblasts towards UV- or tobacco smoking-induced MMP-1 expression. CONCLUSION: Tobacco smoke and UVA cause wrinkle formation independently of each other. We propose that both factors cause aging of human skin through additive induction of MMP-1 expression.

Adult↗

Evaluation of spinal cord blood flow during prostaglandin E1-induced hypotension with power Doppler ultrasonography.

STUDY DESIGN: Intraoperative power Doppler ultrasonography was used to evaluate the spinal cord blood flow in cervical spondylotic myelopathy patients during hypotensive anesthesia. OBJECTIVE: To evaluate the effect of prostaglandin E1 (PGE1) induced hypotension on spinal cord blood flow (SBF) during spinal surgery. SUMMARY AND BACKGROUND DATA: Hypotension is frequently induced to decrease blood loss during surgery and to diminish the need for blood transfusion. Prostaglandin E1 (PGE1) is reported to maintain cerebral, liver, and renal blood flow during surgery. However, there are few reports on spinal cord blood flow. METHODS: Eleven patients underwent laminoplasty for cervical spondylotic myelopathy. After a French door type laminoplasty was carried out, hypotension was induced with PGE1. Before and during hypotension, we evaluated blood flow in the anterior spinal cord artery by determining the pulsatility index (PI) and resistance index (RI) using power Doppler ultrasonography. RESULTS: Before hypotension, the mean blood pressure was 80 mmHg. The blood pressure decreased to 60 mmHg using PGE1 (P<0.01), although the PI and RI were significantly higher than before hypotension (PI, P=0.0076 RI, P=0.02). CONCLUSION: The pulsatility and resistance indices during hypotension were significantly higher than before hypotension, suggesting that the autoregulation of the anterior spinal cord artery and anterior spinal cord blood flow were maintained with hypotension using PGE1. Prostaglandin E1 may be a useful drug for hypotensive anesthesia in spinal surgery.

Adolescent↗

cDNA cloning and genetic polymorphism of the swine major histocompatibility complex (SLA) class II DMA gene.

cDNA clones corresponding to the swine histocompatibility complex (SLA: swine leucocyte antigen)-DM alpha chain were isolated using the polymerase chain reaction (PCR) products from the third exon in the human HLA-DMA gene as a probe. Amino acid comparative analysis revealed that these clones were more closely related to the bovine and human DMA genes than to the other swine class II genes alpha chain genes, DRA, DQA and DOA. These results suggest that the SLA-DMA gene is expressed and may function, like HLA-DM, as an important modulator in class II restricted antigen processing in swine. Furthermore, based on the sequences and PCR-restriction fragment length polymorphism (PCR-RFLP) patterns in the SLA-DMA gene, no allelic variation was recognized in the second exon, but five allelic variations were recognized in the third exon in five different breeds of swine. These DMA alleles were defined by variation at four nucleotide positions. Two of these alleles resulted in an amino acid substitution. These results suggest that SLA-DMA has little polymorphism as observed in HLA-DMA and mouse H2-Ma.

Alleles↗