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Biomedical subjects

T Hasebe

Publications and source records attributed to T Hasebe.

At least 73 records · Page 4Linked to original sources

Factors affecting depth of gastric ulcers.

PURPOSE: We investigated the differences in background factors, clinical features, and gastric function tests among gastric ulcers of various depths. PATIENTS AND METHODS: The subjects were 68 patients (male 64, female 4) who were diagnosed as having a gastric ulcer at the angulus. The ulcers were classified according to depth based on the following: UL2 (shallow) ulceration to the submucosa; UL3 (intermediate), to the muscularis propria; and UL4 (deep excavation), beyond the muscularis propria. The depth of each ulcer was determined by endoscopic ultrasonography and/or ordinary endoscopic findings. We assessed clinical features, age, gender, smoking habit, alcohol consumption, ulcer history, presence of H. pylori, gastric acid secretion, gastric emptying, serum gastrin level, healing rate, and recurrence rate. RESULTS: Patients with UL4-type ulcers had a higher rate of recurrence and a significantly higher incidence of H. pylori infection. Patients with hyperacidity and currently smoking or consuming alcohol were significantly more likely to have UL4-type ulcers than of UL2 or 3 ulcers. Furthermore, a close relationship was recognized between recurrence, intractability and deeply excavated ulcers. Ulcer depth was not correlated significantly with any of the following factors: 1) patient's profile; including gender and hemorrhagic symptoms; 2) gastric function; including gastric emptying and serum gastrin levels. CONCLUSIONS: Smoking, alcohol consumption, recurrence of ulcers, hyperacidity and H. pylori infections are important factors associated with deep ulcers.

Female↗

Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

We investigated the utility of examining biological markers to predict chemoresponse and survival. The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum. The expression of p53, bcl-2, thymidylate synthase (TS), glutathione S-transferase pi (GST-pi), and vascular endothelial growth factor (VEGF) in the formalin-fixed biopsy samples of primary tumors before chemotherapy was examined immunohistochemically. The positive rate for VEGF, bcl-2, TS, p53, and GST-pi was 51, 10, 46, 38, and 69%, respectively. VEGF-positive cases showed a higher response rate than did negative cases (11 of 20 versus 2 of 19 cases; P = 0.0057). The cases that were negative for p53, TS, bcl-2, and GST-pi were more likely to respond to chemotherapy than the cases that were positive for these markers. The 10 cases having 4 or 5 favorable phenotypes (VEGF positive, p53 negative, bcl-2 negative, TS negative, and GST-pi negative) survived longer than the remaining 29 cases (P = 0.0069). Multivariate analysis revealed that the number of favorable phenotypes (> or = 4 versus < or = 3) had a greater impact on survival than performance status (0 versus 1 or 2), age (> 60 years versus < or = 60 years), macroscopic type (scirrhous versus nonscirrhous), histological type (intestinal versus diffuse), or tumor extent (locally advanced versus metastatic). Immunohistochemical examination of biological markers in biopsy samples may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

Adult↗

Dictyostelium IQGAP-related protein specifically involved in the completion of cytokinesis.

The gapA gene encoding a novel RasGTPase-activating protein (RasGAP)-related protein was found to be disrupted in a cytokinesis mutant of Dictyostelium that grows as giant and multinucleate cells in a dish culture. The predicted sequence of the GAPA protein showed considerable homology to those of Gap1/Sar1 from fission yeast and the COOH-terminal half of mammalian IQGAPs, the similarity extending beyond the RasGAP-related domain. In suspension culture, gapA- cells showed normal growth in terms of the increase in cell mass, but cytokinesis inefficiently occurred to produce spherical giant cells. Time-lapse recording of the dynamics of cell division in a dish culture revealed that, in the case of gapA- cells, cytokinesis was very frequently reversed at the step in which the midbody connecting the daughter cells should be severed. Earlier steps of cytokinesis in the gapA- cells seemed to be normal, since myosin II was accumulated at the cleavage furrow. Upon starvation, gapA- cells developed and formed fruiting bodies with viable spores, like the wild-type cells. These results indicate that the GAPA protein is specifically involved in the completion of cytokinesis. Recently, it was reported that IQGAPs are putative effectors for Rac and CDC42, members of the Rho family of GTPases, and participate in reorganization of the actin cytoskeleton. Thus, it is possible that Dictyostelium GAPA participates in the severing of the midbody by regulating the actin cytoskeleton through an interaction with a member of small GTPases.

Amino Acid Sequence↗

Intraductal papillary tumors and mucinous cystic tumors of the pancreas: clinicopathologic study of 38 cases.

Clinicopathological features of 28 patients with intraductal papillary tumor (IDPT) and 10 patients with mucinous cystic tumor (MCT) of the pancreas were studied. Both IDPT and MCT showed papillary projections of the epithelium with abundant mucus secretion in the ectatic ducts or cystic spaces. The patients with IDPT comprised 19 men and 9 women with a mean age of 64.9 years. Three fourths of the IDPTs were located in the pancreatic head, and the mean tumor size was 3.5 cm. Local recurrence was observed in one patient, but none died of IDPT. In contrast, all patients with MCT were women, with a mean age of 49.4 years. None of the MCTs arose in the head, and the mean tumor size was 7.1 cm. One patient died of MCT, but all of the others survived without recurrence. Eight IDPTs and three MCTs showed invasion into the surrounding pancreatic tissue. Muconodular infiltration was mainly observed in five IDPTs and one MCTs and tubular infiltration in three IDPTs and two MCTs. A characteristic histological finding associated with the muconodular infiltration in IDPT was subepithelial "mucin droplets" that appeared to represent a change in polarity of mucus secretion. The formation of such subepithelial "mucin droplets" may be the initial step of muconodular infiltration in IDPT. Muconodular infiltration in IDPT appears different morphologically and biologically from the mucinous carcinoma subtype of conventional invasive ductal carcinoma.

Adenocarcinoma, Papillary↗

Idiopathic granulomatous mastitis: case report and review of the literature.

We report a case of idiopathic granulomatous mastitis in a 35-year-old Japanese woman, who came to our hospital complaining of a tender mass in her right breast. Because the results of initial aspiration cytology were considered highly suspicious for carcinoma, modified radical mastectomy was performed. However, the final histological diagnosis was granulomatous lobular mastitis with no evidence of malignancy. Idiopathic granulomatous mastitis is a rare inflammatory breast disease of unknown etiology. Since the clinical manifestations are similar to those of mammary carcinoma, this condition has been misdiagnosed as carcinoma and treated as such. A review of the literature revealed that idiopathic granulomatous mastitis has tended to occur in young patients with a history of childbirth or oral contraceptive usage. Clinical or imaging diagnosis has often been difficult. Complete resection or corticosteroid therapy can be recommended as the optimal treatment. Since 38% of patients experience recurrence, long-term follow-up is indicated.

Adrenal Cortex Hormones↗

Coxalgia as the initial symptom in Hodgkin's disease: a case report.

Primary Hodgkin's disease in the bone is extremely rare. We report the case of a 41-year-old woman with Hodgkin's disease, who had complained of left coxalgia 17 months prior to nodal involvement becoming evident clinically. She received combination chemotherapy with doxorubicin, bleomycin, vincristine and dacarbazine as well as radiotherapy to the pelvic lesion. Although the lymphadenopathy responded well to this treatment, the bone lesion was never in remission. The large mass of the bone lesion and its pelvic origin may explain the poor response to the cytotoxic therapies this patient received. The 22 cases reviewed showed that: 1, bony pain was the most frequent initial symptom; 2, nodal disease appeared in their clinical course in most cases; 3, the bones most commonly involved were pelvis, femur or tibia, and spine.

Adult↗

Structure and function in Escherichia coli of plasmids containing pyrimidine/purine-biased stretch originated from the 5'-flanking region of the basidiomycete ras gene.

The Basidiomycete ras gene possesses a pyrimidine-rich stretch (CT-motif) with a short (7 bases) mirror repeat in which its major transcription start point is contained. To analyze the tertiary structure induced by the CT/AG-biased sequence and its effect on gene expression in supercoiled plasmids in Escherichia coli, the DNA fragment containing the ras CT/AG sequence was inserted into the EcoRI site on pBR322 in both orientations and the resulting pBR322 derivatives, named pBR-CT[ras] and pBR-invCT[ras] were introduced into E. coli strains DM800 (deltatopA gyrB225) and JM109 (topA+ gyrA96). In pBR-CT [ras] the pyrimidine-rich sequence is on the pBR322 tetracycline-resistance gene (tet)coding strand and in pBR-invCT[ras] the complementary purine-rich sequence is on this strand. DNAs of pBR-CT[ras] and pBR-invCT[ras] isolated from DM800 were frequently cleaved with single-strand-specific S1 nuclease within the CT/AG sequence, showing the formation of extended open structure. Compared with those carrying pBR322, DM800 and JM109 carrying pBR-CT [ras] showed much higher levels of tetracycline resistance (Tcr), while both strains carrying pBR-invCT[ras] showed clearly lower levels of Tcr. pBR-CT [ras] and pBR-invCT [ras], however, conferred reduced activity of beta-lactamase on DM800 and JM109. pBR-CT [ras] derivatives lacking the counterpart of the mirror repeat did not form the S1-cleavable open structure within the CT/AG sequence and conferred pBR322-like Tcr and beta-lactamase activity. The tertiary structure formed in the CT/AG sequence via the mirror repeat was suggested to affect the expressions of pBR322-tet and -bla genes.

Base Sequence↗

Induction of aberrant crypt foci and flat-type adenocarcinoma in the colons of dogs by N-ethyl-N'-nitro-nitrosoguanidine and their sequential changes.

Sequential endoscopic observation of dog colons was performed during colon carcinogenesis. Two beagle dogs were given suppositories containing N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) every day for five months. In month 3, aberrant crypt foci (ACF), a putative preneoplastic lesion, were found in the colons of both dogs, but not in an untreated dog. The frequency of ACF increased until month 10, and then decreased. In month 9, very small lesions, less than 1 mm in diameter, which were similar to human early flat tumors, were first noticed. One of these lesions grew to about 7 mm in size without a change in its shape for 10 months. There were more than ten flat-type tumors in the two dogs, but such lesions were not found in the untreated dog. By biopsy, two of the lesions were proved to be well-differentiated adenocarcinomas histologically. Four polypoid lesions were found in one of the carcinogen-treated dogs. Thus, flat-type adenocarcinomas were induced in the dog colon by ENNG, and their development was followed by magnifying endoscopy.

Adenocarcinoma↗

Application of image analysis and neural networks to the pathology diagnosis of intraductal proliferative lesions of the breast.

We studied whether a computer-assisted system using a combination of data collection by image analysis and analysis by neural networks can differentiate benign and malignant breast lesions. Forty-six intraductal lesions of the breast were studied by pathologists and by the computer-assisted system. Histological evaluation was performed independently by three pathologists, and the lesions were classified into pathologically malignant (n = 12), undetermined (n = 13), and benign (n = 21). Computerized nuclear image analysis was performed using the CAS200 (Cell Analysis Systems, Elmhurst, IL) system to obtain data on nuclear morphometric and textural features. A neural network was constructed using the morphometric and texture data obtained from teaching cases of malignant and benign lesions. Then data for unknown cases were classified by the constructed neural network into neural network-malignant (n = 11), -undetermined (n = 5), and -benign (n = 30). The agreement rate between the diagnosis by pathologists and judgment by the computer-assisted system was 75%, excluding pathologically undetermined lesions. There were four false-negative but no false-positive results. False-negative cases had nuclei that were quite different from those of the teaching cases. The agreement rate obtained using either morphometric data or texture data only was lower than that using a combination of both. Selection of appropriate teaching data and incorporation of both morphometric and textural parameters seemed important for obtaining more accurate results. The present data suggest that development of a computer-assisted histopathological diagnosis system for practical use may be possible.

Breast↗

Fibrotic focus in invasive ductal carcinoma of the breast: a histopathological prognostic parameter for tumor recurrence and tumor death within three years after the initial operation.

We investigated whether the presence of a fibrotic focus (FF) in the primary lesion and in lymph node metastasis is a good predictor of early tumor recurrence or death in patients with invasive ductal carcinoma (IDC). Multivariate relative risk (RR) of tumor recurrence and death according to the presence of FF in the primary tumor was estimated using the Cox proportional hazards regression model with adjustment for other prognostic factors (histologic grade, T classification, nodal status, tumor necrosis, DNA ploidy, c-erbB-2 protein expression, p53 protein expression, and labeling index of proliferating cell nuclear antigen). For the evaluation of the metastatic status in the axillary lymph nodes, RR of multivariate analysis was adjusted for the presence of FF in the metastatic tumor and the number of lymph nodes involved (1-3 and > 3). The presence of FF increased the RR of tumor recurrence significantly for the cases in all stages, and especially for those in stages I and II (RR = 6.9, P < 0.05 and RR = 25.0, P < 0.005, respectively). All cases that died of disease had FF. Among IDCs with FF, 24 cases had FF in lymph node metastasis. Significantly higher RRs of tumor recurrence and death were observed in cases with FF in lymph node metastasis than in those without it (RR = 2.0, P < 0.001 and RR = 5.9, P < 0.05, respectively). It was suggested that the presence of FF is an important predictor of early tumor recurrence or death in patients with IDCs. The presence of FF in lymph node metastatic lesions is also a significant prognostic parameter.

Adult↗

Significance of basic fibroblast growth factor and fibroblast growth factor receptor protein expression in the formation of fibrotic focus in invasive ductal carcinoma of the breast.

A fibrotic focus (FF) is a scar-like area within invasive ductal carcinoma (IDC) of the breast, and has been shown to be a marker of high aggressiveness of IDC. In order to investigate the mechanism of FF formation in IDC, expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor (FGFR) was studied. One hundred and forty-nine IDCs were divided into solid tumors and scirrhous tumors. Immunohistochemistry was used to determine the expression of bFGF and FGFR proteins in both tumor cells and fibroblasts forming FF. Scirrhous tumors with FF showed a significantly higher frequency of bFGF protein expression than those without (P = 0.017), whereas, in solid tumors, the presence of FF was not significantly associated with the frequency of bFGF protein expression (P = 0.143). In addition, scirrhous tumors showed a significantly higher frequency of FGFR protein expression than solid tumors (P = 0.001). Among IDCs having FF and expressing bFGF protein, a significantly larger number of fibroblasts expressing FGFR protein within FF was observed in scirrhous tumors than in solid tumors (P = 0.016). The results of this study suggest that in scirrhous tumors the interaction between tumor cells and stromal fibroblasts plays an important role in the formation of FF, and that there is a paracrine mechanism between bFGF protein from tumor cells and FGFR protein in fibroblasts.

Adenocarcinoma, Scirrhous↗

High frequency of K-ras mutations in human colorectal hyperplastic polyps.

BACKGROUND: Hyperplastic polyps are common benign colorectal polyps, and are thought to have little association with malignant tumours in the colorectum. However, several reports suggest that some hyperplastic polyps may develop into colorectal neoplasms. AIM: To clarify genetic alterations in colorectal hyperplastic polyps. METHODS: Twenty eight colorectal polyps having serrated components were resected from patients endoscopically. The K-ras gene mutations in codons 12 and 13 were analysed by PCR-RFLP. Intranuclear p53 protein was immunostained by the avidin-biotin complex method. RESULTS: A mutation of the K-ras gene was detected in nine (47%) of 19 hyperplastic polyps, and five (56%) of nine adenomas. p53 protein nuclear accumulation was detected immunohistochemically in two (22%) of nine adenomas, but not in any of the hyperplastic polyps. CONCLUSION: Some hyperplastic polyps may be true neoplastic lesions, and could be precursors of malignant neoplasia.

Adenoma↗

A case of extragonadal germ cell tumor with elevated postchemotherapy HCG successfully treated by resection of a solitary metastasis and chronic oral etoposide.

We report a 39 year-old man with disseminated extragonadal germ cell tumor (GCT), whose serum level of human chorionic gonadotropin (HCG) increased again after platinum-based combination chemotherapy, high-dose chemotherapy with autologous bone marrow rescue and radical adjunctive surgery. The increase in the HCG level was progressive in spite of multiple chemotherapy, and after a while, a coin lesion in the right lung was identified by chest roentgenography. The pulmonary lesion was refractory to additional chemotherapy. After a systemic survey to confirm that the lesion was solitary, video-assisted thoracoscopic wedge resection of the right lower lobe was performed. Because the resected tumor included viable tumor cells and the serum HCG level remained slightly high one month after the operation, oral low-dose etoposide was begun. In a short time, the level of the serum tumor marker decreased and remained normal during the subsequent 7 months of therapy and thereafter. The patient remains in complete remission 13 months after completion of the final therapy and 3 years after the initial diagnosis. Even if the level of a serum tumor marker is high, salvage resection can be a promising therapeutic option for operable tumors that are refractory to chemotherapy. The usefulness of chronic oral etoposide for patients with GCT should be examined by further clinical trials.

Administration, Oral↗

Association of p53 protein expression with responses and survival of patients with locally advanced esophageal carcinoma treated with chemoradiotherapy.

Immunohistochemical analysis was performed to determine the clinical role of p53 mutations in patients with locally advanced esophageal carcinomas treated with concurrent chemoradiotherapy. The subjects of this study were 20 patients with previously untreated esophageal carcinomas with evidence of T4 disease and/or distant node metastases. Treatment comprised protracted 5-fluorouracil and 2-h cisplatinum infusions along with radiation treatment with a total radiation dose of 60 Gy. Tumor specimens from 18 of the 20 patients were analyzed immunohistochemically. Mutant p53 protein expression in the biopsy materials from the primary tumors was analyzed by immunohistochemical staining using a polyclonal antibody, RSP53. Expression of p53 was detected immunohistochemically in 10 (56%) of the 18 esophageal tumors, the cancer cell nuclei of which were diffusely stained. There were no significant differences between the patient backgrounds of the p53-"positive" and "negative" groups. Four (40%) of the 10 patients with p53 expression achieved overall complete remissions (CRSs) and 7 (70%) of these 10 achieved CRs of their primary tumors. In contrast, none of the 8 p53-negative patients achieved overall CRs and two (25%) achieved CRs of their primary tumors. The CR rates overall and of primary tumors tended to be higher in the p53-positive than negative group, but the differences were not significant. The survival rate for the 10 patients with p53 expression was better than that for the 8 negative ones (P>0.01): their median survival times were 12 and 4.5 months, respectively. Expression of p53 protein may be an indicator of a favorable prognosis in patients with locally advanced esophageal carcinomas treated with concurrent chemoradiotherapy.

Aged↗

Fibrotic focus in invasive ductal carcinoma: an indicator of high tumor aggressiveness.

Histological examination of invasive ductal carcinoma of the breast often demonstrates the presence of an extensive central fibrotic focus (FF). The clinicopathological significance of the FF, or scar, in primary invasive ductal carcinoma is still ambiguous. One hundred and fifty-three cases of invasive ductal carcinoma (IDC) were classified into two groups, those with and those without FF. The differences in frequency of immunohistochemically detected overexpression of c-erbB-2 protein and nuclear accumulation of p53 protein, and the labeling index of proliferating cell nuclear antigen (PCNA), as well as histopathological parameters were compared between these two groups. IDCs smaller than 50 mm with FF showed a higher frequency of high-grade tumors, a higher frequency of lymph node metastasis, and a significantly higher frequency of c-erbB-2 protein overexpression than those without FF. In tumors of 20 mm or less, the incidence of nuclear accumulation of p53 protein was significantly higher in tumors with than those without FF. Tumors with FF showed a significantly higher PCNA labeling index than those without FF, regardless of tumor size. The present results indicate that the presence of FF is an important clinicopathological parameter associated with a higher degree of malignancy in IDCs, especially those smaller than 50 mm. Therefore, dividing IDCs into those with and those without FF appears to be meaningful clinicopathologically.

Adult↗

Aberrant expression of a hemidesmosomal protein, bullous pemphigoid antigen 2, in human squamous cell carcinoma.

Through yet unidentified mechanisms, squamous epithelial cells become committed to terminal differentiation after detachment from the basement membrane. In squamous cell carcinoma, these mechanisms seem to be disturbed. A murine monoclonal antibody, designated NCC-Lu-226 (IgG1, K), which recognizes an antigen expressed in basal cells of squamous epithelium at the epithelio-connective tissue border, was obtained. A cDNA clone encoding the antigen was isolated from a cDNA library by immunoselection. DNA sequencing and a database search revealed that this cDNA clone was identical to a hemidesmosomal transmembrane protein, bullous pemphigoid antigen 2 (BPA-2; also known as BPAG2, BP180, or type XVII collagen). Immunoelectron microscopy validated the specific reactivity of this monoclonal antibody with skin hemidesmosomes. Enhanced expression and abnormal distribution of BPA-2 was revealed immunohistochemically in various precancerous and cancerous tissues, including solar keratosis (4 of 5), Bowen's disease (3 of 5), invasive squamous cell carcinoma (7 of 7) of the skin, and squamous cell carcinoma of the lung (14 of 14), esophagus (12 of 13), and cervix (14 of 17). The specific expression of BPA-2 protein in squamous cell carcinoma was confirmed by RT-PCR and Northern hybridization. BPA-2 has possible phosphorylation sites and is actually phosphorylated in cultured keratinocytes and squamous cell carcinoma. The aberrant expression of BPA-2 may reflect dysfunction of the hemidesmosome that occurs as a relatively early event in multistep carcinogenesis of squamous epithelium.

Antibodies, Monoclonal↗

Emergence of adenomatous aberrant crypt foci (ACF) from hyperplastic ACF with concomitant increase in cell proliferation.

To investigate the relationship between aberrant crypt foci (ACF) and colon neoplasia in colorectal carcinogenesis, we evaluated 433 ACF, which were collected from the grossly normal mucosa of surgical specimens from 57 patients with colorectal cancer. The ACF ranged in size from 3 to 412 aberrant crypts/focus. Large ACF (> or = 50 crypts/focus) comprised 25% of the total ACF studied. Histopathologically, 65% (67 of 103) of large ACF were diagnosed as hyperplasia, 10% (10 of 103) as adenoma, and 1% (1 of 103) as within normal colorectal mucosa. The remaining 24% (25 of 103) were diagnosed as "stage I abnormality crypts," which were characterized by their extension of the proliferative compartment to the surface of crypts but with no changes in the major site of proliferation, as designated by E. E. Deschner [Pathol. Annu., 18 (Part 1): 205-219, 1983]. Of the 25 stage I abnormality ACF, 7 ACF coexisted with hyperplasia. Of 10 adenomatous ACF, two coexisted with stage I abnormality crypts. A K-ras codon 12 mutation was identified in 85% (93 of 109) of large ACF. The proliferative activity of stage I crypts was significantly higher than that of hyperplastic crypts in the same ACF. These observations suggest that some hyperplastic ACF may develop into adenomatous ACF by way of stage I abnormality ACF with concomitant acquisition of higher proliferative activity through some genetic and/or epigenetic changes.

Adult↗