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M Tsujimoto

Publications and source records attributed to M Tsujimoto.

At least 19 recordsLinked to original sources

Molecular cloning of adipocyte-derived leucine aminopeptidase highly related to placental leucine aminopeptidase/oxytocinase.

In the current study, we report the cloning and initial characterization of a novel human cytosolic aminopeptidase named adipocyte-derived leucine aminopeptidase (A-LAP). The sequence encodes a 941-amino acid protein with significant homology (43%) to placental leucine aminopeptidase (P-LAP)/oxytocinase. The predicted A-LAP contains the HEXXH(X)18E consensus sequence, which is characteristic of the M1 family of zinc-metallopeptidases. Although the deduced sequence contains a hydrophobic region near the N-terminus, the enzyme localized mainly in cytoplasm when expressed in COS-7 cells. Northern blot analysis revealed that A-LAP was expressed in all the tissues tested, some of which expressed at least three forms of mRNA, suggesting that the regulation of the gene expression is complex. When aminopeptidase activity of A-LAP was measured with various synthetic substrates, the enzyme revealed a preference for leucine, establishing that A-LAP is a novel leucine aminopeptidase with restricted substrate specificity. The identification of A-LAP, which reveals strong homology to P-LAP, might lead to the definition of a new subfamily of zinc-containing aminopeptidases belonging to the M1 family of metallopeptidases.

Adipocytes

Clinicopathological significance of poorly differentiated thyroid carcinoma.

The clinicopathological importance of a heterogeneous group of poorly differentiated thyroid carcinomas is not fully understood. Using data obtained from 303 surgically treated patients with differentiated thyroid carcinomas, the correlations between the aggressive histologic features and the clinicopathological findings, postoperative recurrences, and prognosis were retrospectively examined. In 201 cases, the carcinomas were well differentiated. The remaining 102 cases of poorly differentiated carcinomas were divided into two groups: focal-poorly differentiated (<10%) and diffuse-poorly differentiated (> or = 10%) carcinomas according to the extent of the poorly differentiated component. These poorly differentiated carcinomas were associated with high age (focal-poorly differentiated and diffuse-poorly differentiated versus well differentiated: 55 years and 59 versus 49; p < 0.0001), frequent presence of lymph node metastases (70% and 66% versus 48%; p = 0.0099) and distant metastases at diagnosis (11% and 11% versus 2%; p = 0.0098), and extrathyroidal invasion (53% and 53% versus 21%; p < 0.0001). There was independent correlation with age and the presence of extrathyroidal invasion. Cases of diffuse-poorly differentiated carcinomas showed frequent relapse (diffuse-poorly differentiated versus focal-poorly differentiated and well differentiated: 45% versus 30% and 24%; p = 0.0062) and poor prognoses (mean survival period = 9.15 versus 19.03 and 20.87 years; p < 0.0001) compared with the well and focal-poorly differentiated carcinomas. These data suggest that diffuse-poorly differentiated carcinoma is an important clinicopathological entity.

Adenocarcinoma, Follicular

Expression of CD44 variant 6 and lymphatic invasion: importance to lymph node metastasis in gastric cancer.

Lymph node metastasis is a critical prognostic factor for gastric cancer. In the present investigation we examined clinicopathologic factors influencing the metastatic processes to the lymph mode and their prognostic importance. A randomly selected group of 98 patients with adenocarcinomas of the stomach who underwent gastrectomy plus systematic lymph node dissection at Osaka Police Hospital from 1991 to 1996 were analyzed. Altogether 37 (38%) cancers were positive for CD44 variant 6 (v6) staining, 31 (32%) were intermediately stained, and 30 (30%) were negative. CD44-v6 expression correlated well with lymph node metastasis. Expression of CD44-v6 and lymphatic invasion were independent risk factors for metastatic lymph nodes. Among the patients with CD44-v6-positive and lymphatic invasion-positive cancers, 88% had lymph node metastasis, whereas only 13% of patients negative for both factors had lymph node metastasis. Although CD44-v6 expression and lymphatic invasion have been reported to be risk factors for recurrence and a poor prognosis, in this investigation these factors were found not to be significant for hematogenous and lymphatic recurrences or overall survival rates. Thus expression of CD44-v6 and lymphatic invasion may regulate lymph node metastases from gastric cancer.

Adenocarcinoma

Significance of biologic aggressiveness and proliferating activity in papillary thyroid carcinoma.

Papillary thyroid carcinoma is a frequent thyroid cancer. Many factors have been reported to be of prognostic importance, but the significance of biologic factors suggesting aggressiveness and proliferating activity has not been sufficiently documented. Conventional prognostic factors such as age, extrathyroidal invasion, lymph node and distant metastasis, and biologic factors including histologic differentiation, DNA ploidy, S-phase and G2M-phase fractions, and expression of CD44 variant 6 (CD44-v6) obtained from 131 patients who underwent surgery for papillary thyroid carcinoma at Osaka Police Hospital were analyzed retrospectively. Age was closely related to extrathyroidal invasion, G2M-phase fraction, and CD44-v6 expression. Extrathyroidal invasion was independently related to age, gender, and lymph node metastasis. The grade of lymph node metastasis was related to extrathyroidal invasion, gender, distant metastasis, and CD44-v6 expression. Distant metastasis was associated with aneuploid tumors. Cause-specific survival was independently related to biologic factors including extrathyroidal invasion, distant metastasis, DNA ploidy and S-phase fraction. These results suggest that biologic factors indicating aggressiveness and proliferating activity are important for papillary thyroid carcinoma.

Aged

Independent prognostic factors in breast cancer patients.

BACKGROUND: Recently tumor microvessel density has been shown to be a powerful prognostic tool in breast cancer. We attempted to assess its significance as a prognostic factor. METHODS: We analyzed the medical records of 100 patients using univariate and multivariate analyses of nine factors as follows; age, tumor size, nodal status, estrogen receptor, C-erbB2, p53, microvessel density, DNA ploidy pattern, and S-phase fraction. RESULTS: Nodal status and microvessel density were independent prognostic indicators for both survival and relapse-free survival. Microvessel density was independent in the node-negative subgroup for survival, but not independent in the node-positive subgroup, while it was independent in both the node-negative and node-positive subgroups for relapse-free survival. Short-term survival rates in the high and low vessel density subgroups were almost the same, and all patients with early death were node-positive. CONCLUSION: Microvessel density was an important prognostic factor especially in node-negative patients and more significant in long-term survival.

Age Factors

Carcinosarcoma of the breast: molecular-biological study for analysis of histogenesis.

The histogenesis of carcinosarcoma of the breast is controversial. In the current case, the demarcation between the carcinomatous and sarcomatous components was distinct in all microscopic fields. Immunohistochemical analysis was negative for epithelial membrane antigen (EMA) and keratin in the sarcomatous component and was negative for desmin in the carcinomatous component, suggesting that this tumor could be derived from the two different stem cells. To determine the histogenesis of this tumor, both carcinomatous and sarcomatous lesions were microdissected from formalin-fixed tissues and DNAs were prepared by proteinase K digestion. PCR amplification of the human androgen receptor (HUMARA) short tandem repeat (STR), after Hpa II digestion of the genomic DNA, indicated that the patterns of X-chromosome inactivation were identical in both components. Moreover, both components contained the identical TGT --> TTT transversion in codon 275 of the p53 gene. These observations strongly support the hypothesis that this tumor is derived from a single totipotent stem cell.

Breast Neoplasms

[Clinical evaluation of lung abscess diagnosed by transtracheal aspiration].

We have diagnosed lung abscess according to findings of infiltration with cavity formation on chest X-ray and/or CT-scan and pathogens isolated from transtracheal aspirates. We evaluated the clinical features of 20 patients with lung abscess (18 males and 2 females, mean age; 54.3 years). Diabetus mellitus and periodontal diseases were prominent underlying diseases in patients with lung abscess. Cough was complained in 13 patients, chest or back pain in 9, purulent sputum in 8 and hemosputum in 5 when the patients admitted to our hospital. A temperature higher than 38 degrees C was present in 12 patients but temperature les than 37 degrees C in 2. Multiple microorganisms were cultured from TTA in 15 patients. A mean of 2.7 bacterial species per patient was isolated, aerobes alone being isolated in 2 patients, anaerobes alone in 3, and mixed aerobic and anaerobic isolates in 10. Seventeen strains of aerobes and 35 of anaerobes were isolated. Major pathogens were Streptococcus pneumoniae, Streptococcus intermedius and other in aerobes, and Peptostreptococcus micros, Fusobacterium necrophorum, Prevotella melaninogenica and others in anaerobes. Abnormality of chest X-ray was located on the right upper lobe in 6 patients, the right lower lobe in 6, the left upper lobe in 6, the left lower lobe in 4 and the right middle lobe in 1. All patients were cured only by treatment of antimicrobial agents, but cavity formation on chest X-ray remained in 4 patients after the treatment.

Adult

[Clinical analysis of patients with sepsis--comparison between underlying diseases].

We evaluated the clinical data in 83 patients with sepsis, which was diagnosed by both Bone's definition of sepsis and positive isolates from blood culture, according to their underlying diseases. This study enrolled a total of 117 septic episodes in 83 patients (57 males and 26 females, mean age: 52.0 years). We classified 3 groups, including hematological malignancies (46 patients, 72 episodes), solid malignant tumors (23 patients, 25 episodes) and non-malignancies (14 patients, 20 episodes), by the underlying diseases. Of the total number of isolates from blood culture, 53.0% were single gram-positive bacteria, 33.3% were single gram-negative bacteria, 7.7% were single fungus and 6.0% were polymicrobial organisms. In addition, coagulase negative staphylococci was isolated most often in patients with hematological malignancies. Sepsis was often caused by infectious focuses of hemorrhoid, stomatitis or intravenous catheter in patients with hematological malignancies, by pneumonia in patients with solid malignant tumors and by urinary tract infection in patients with non-malignancies. Mortality of sepsis in patients with solid malignant tumors (48%) was highest in 3 groups. Septic patients, who were complicated with shock and/or DIC, has poor prognosis in all groups. Serum albumin level was significantly lower in dead patients than patients who survived. These results suggest that clinical features may be different according to the underlying diseases of patients with sepsis.

Aged

[An epidemiological investigation for MRSA and PRSP in Kinki area. Kinki Infection Working Group].

Recent trends in the development of resistance of the Staphylococcus aureus and Streptococcus pneumoniae to antibiotics were investigated, using a questionnaire delivered to participants at a meeting of the Kinki District Society of Infections. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 55.4% of all isolated S. aureus, and more than 80% of MRSA was detected within hospitals. In outpatients, MRSA was often detected in pus, while in hospitalized patients, MRSA was often detected in sputum. Further, MRSA was accompanied by some other organisms (most frequently Pseudomonas aeruginosa) in 64.7% of MRSA positive patients. The sensitivity of MRSA to vancomycin (VCM) was 100%, to sulfamethoxazole-trimethoprim (ST) 99.2%, and to arbekacin, 98.6%. In contrast, Penicillin-resistant Streptococcus pneumoniae (PRSP) accounted for 42.4% of all isolates of Streptococcus pneumoniae. About 50% of PRSP was detected in out-patients. For both hospitalized patients and outpatients, PRSP was most frequently detected in sputum. PRSP was accompanied by some other organisms (most frequently Haemophilus influenzae) in 49.3% of PRSP positive patients, PRSP had high sensitivity to cephems, carbapenems and VCM.

Aminoglycosides

[Leydig cell tumor of the testis: a case report].

A 63-year-old male visited our hospital with a complaint of painless swelling of the left scrotum. Left high orchiectomy was performed since ultrasonography suggested a testicular tumor. Histologically, this testicular mass was a Leydig cell tumor. We reviewed 47 cases of this tumor previously reported in Japan.

Humans

Somatic mutations of multiple endocrine neoplasia type 1 gene in the sporadic endocrine tumors.

Endocrine tumors of the parathyroid and pancreas are encountered either as sporadic type or as part of multiple endocrine neoplasia type 1 (MEN 1). A high frequency of the loss of heterozygosity (LOH) has been observed in tumors of the sporadic type in the locus of the MEN 1 gene, which has recently been cloned and designated the menin gene. It would be of great interest to determine whether somatic mutations in the menin gene are responsible for the sporadic endocrine tumors. For this purpose, we have investigated the menin gene mutations in 21 sporadic parathyroid adenomas, 2 parathyroid carcinomas, 4 sporadic insulinomas, and 1 malignant VIP (vasoactive intestinal polypeptide)oma with WDHA (watery diarrhea, hypokalemia, and achlorhydria) syndrome, using PCR-single strand conformation polymorphism analysis and DNA sequencing. In none of these cases did the patient have a family history or other possible association with MEN 1. We have discovered somatic point mutations in two parathyroid adenomas (A340T and A541T), in one insulinoma (T429K), and in the malignant VIPoma (W198X). In addition, we have found two polymorphisms (D418D and V367V) in two parathyroid carcinomas and two parathyroid adenomas. Of these mutations and polymorphisms, three (A340T, T429K, and V367V) are first reported here, in the present article. Our results indicate that somatic mutations of the menin gene are responsible for a proportion of the sporadic parathyroid adenomas and pancreatic islet cell tumors.

Adenoma

[Primary carcinoma in situ of the ureter: a case report].

A 55-year-old male visited our hospital with a complaint of gross hematuria and right lower abdominal pain. Cytological findings of voided urine suggested the presence of malignant cells. Cystoscopic examination revealed bloody urine discharge from the right ureteral orifice and no abnormality in the bladder wall. The retrograde pyelogram showed no tumor masses. However, malignant cells were detected cytologically in the right ureteral catheteral urine twice. Under the preoperative diagnosis of primary urothelial tumor of the right upper urinary tract, right total nephroureterectomy was performed. A histological study revealed transitional cell carcinoma in situ in the lower portion of the ureter. We reviewed 46 cases of primary carcinoma in situ of the upper urinary tract previously reported in Japan.

Carcinoma in Situ