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Biomedical subjects

M Tsujimoto

Publications and source records attributed to M Tsujimoto.

At least 91 records · Page 5Linked to original sources

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↗

[Small cell lung cancer associated with nephrotic syndrome: remission after chemotherapy].

A 66 year-old man was found to have pointed out a 1-cm tumor shadow, on a chest X-ray film when he underwent a gastrectomy because of advanced gastric cancer. Five months after the operation, edema and proteinuria developed, and a chest X-ray film revealed enlargement of the tumor. There was no sign of recurrence of the gastric cancer. Nephrotic syndrome due to IgA-nephropathy and small cell lung cancer was diagnosed. Chemotherapy (carboplatin and etoposide) was effective against both the lung tumor and the nephrotic syndrome. Small cell lung cancer may have been involved in the pathogenesis of the nephrotic syndrome in this patient.

Antineoplastic Combined Chemotherapy Protocols↗

Expression cloning of a novel scavenger receptor from human endothelial cells.

Scavenger receptors mediate the endocytosis of chemically modified lipoproteins, such as acetylated low density lipoprotein (Ac-LDL) and oxidized LDL (Ox-LDL), and have been implicated in the pathogenesis of atherosclerosis. The evidence that endothelial cells possess scavenger receptor activity is substantial, and this property is widely used in the isolation of endothelial cells from vascular tissues. In the current study, we have isolated, by expression cloning, the cDNA encoding a novel type of scavenger receptor expressed by endothelial cells (SREC), which mediates the binding and degradation of Ac-LDL. The primary structure of the molecule has no significant homology to other types of scavenger receptors, including the recently cloned endothelial cell Ox-LDL receptor, a member of the C-type lectin family. The cDNA encodes a protein of 830 amino acids with a calculated molecular mass of 85, 735 Da (mature peptide). Chinese hamster ovary cells stably expressing SREC bound 125I-labeled Ac-LDL with high affinity (Kd = 3.0 microg/ml, approximately 1.7 nM) and degraded them via an endocytic pathway. Association of DiII-Ac-LDL were effectively inhibited by Ox-LDL, malondialdehyde-modified LDL, dextran sulfate, and polyinosinic acid, but not by natural LDL and heparin. The cloned receptor has several characteristic domain structures, including an N-terminal extracellular domain with five epidermal growth factor-like cysteine pattern signatures and an unusually long C-terminal cytoplasmic domain (391 amino acids) composed of a Ser/Pro-rich region followed by a Gly-rich region.

Amino Acid Sequence↗

Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors.

The pathogenesis of carcinosarcoma is still a subject of controversy. In the present study, molecular techniques were applied to determine the pathogenesis of uterine carcinosarcomas. The patterns of chromosome X inactivation were analyzed, targeting a portion of exon 1 of the human androgen receptor (HUMARA) in malignant epithelial and mesenchymal components. The presence of p53 and K-ras mutations were also analyzed. H&E-stained sections of paraffin-embedded, formalin-fixed tissues were microdissected to obtain both epithelial and nonepithelial lesions from 25 carcinosarcomas, and DNAs were extracted by proteinase K digestion. Following treatment with methylation-sensitive restriction endonuclease (HhaI or HpaII), PCR amplification was performed using nested primers targeted to the HUMARA locus. Mutations in the p53 gene and K-ras gene were found in eight (32%) and six (24%) tumors, respectively. The patterns of chromosome X inactivation were different between the carcinomatous and sarcomatous components of three carcinosarcomas, indicating that these three tumors represent collision tumors. By contrast, the patterns of chromosome X inactivation, K-ras sequence, and p53 sequence were identical in both carcinomatous and sarcomatous components in 21 carcinosarcomas, indicating that these 21 tumors represent combination tumors. One case produced equivocal results that precluded determination of whether it represented a collision or combination tumor. These observations show that although most carcinosarcomas are combination tumors, some develop as collision tumors. The determination of histogenesis in individual cases of carcinosarcoma using molecular markers may be worthwhile, because the result could help predict the prognosis of individual cases and help guide clinical management.

Adult↗

Purification, cDNA cloning, and characterization of a new serpin with megakaryocyte maturation activity.

A new member of the serine protease inhibitor (serpin) superfamily with megakaryocyte maturation activity was purified, and its cDNA was cloned and characterized. The predicted amino acid sequence consisting of 380 residues was unique and was 38% identical to the serpin plasminogen activator inhibitor type 2 (PAI-2). The recombinant factor expressed in Chinese hamster ovary cells showed species-specific activity on the induction of megakaryocyte maturation in vitro. When injected into mice, the factor indeed elicited an increase in the number of platelets in plasma. The sequence alignment indicated that the factor possessed a lysine residue at the P1 position, suggesting that it might function as an inhibitor of Lys-specific proteases. Although we could not show any inhibitory activities toward several known Lys-specific proteases, we detected the activity toward protease activity present in the culture supernatant of COLO 201 cells. These results suggested that the protein might influence the maturation of megakaryocytes via action as a serpin.

Amino Acid Sequence↗

cDNA cloning and expression of chicken aminopeptidase H, possessing endopeptidase as well as aminopeptidase activity.

Chicken aminopeptidase H is a cysteine protease possessing endopeptidase as well as aminopeptidase activity [Rhyu, M. R., Nishimura, T., Kato, Y., Okitani, A. & Kato, H. (1992) Eur. J. Biochem. 208, 53-59]. This enzyme exhibits molecular masses of 400 kDa on gel filtration and 52 kDa on SDS/PAGE, indicating that it consists of eight subunits with the same molecular mass. In the current study, we cloned the cDNA for the catalytic subunit of chicken aminopeptidase H. The open reading frame of the aminopeptidase H gene consists of 1362 base pairs encoding a 52-kDa protein consistent with the molecular mass determined on SDS/PAGE; the deduced amino acid sequence contains all the partial sequences determined for the purified enzyme. The sequence is similar to that of the bleomycin hydrolase of rabbit lung, which has been partially determined. The recombinant 52-kDa protein expressed in COS7 cells exhibited both aminopeptidase and endopeptidase activities, which were inhibited by monoiodoacetic acid. Furthermore, the expression of aminopeptidase H in COS7 cells was also recognized on immunoblotting. This gene is the first one for aminopeptidase H in an animal tissue whose sequence has been completely determined.

Amino Acid Sequence↗

Differential tissue distribution of the beta- and gamma-subunits of human cytosolic platelet-activating factor acetylhydrolase (isoform I).

The cDNA for human platelet-activating factor acetylhydrolase (PAF-AH) beta-subunit was cloned. The complete amino acid sequence deduced from cDNA contains 229 amino acids and is completely identical with that of the bovine subunit. Moreover, the sequence of the human beta-subunit protein shows 62.4% identity with the human gamma-subunit at the amino acid level. Southern blot analysis suggested the presence of multiple genes and we indeed found another closely related pseudo gene. Northern blot analysis showed that the 4.0 kb transcript was expressed in all tissues tested, suggesting the ubiquitous distribution of the subunit protein. Differential distribution of beta- and gamma-subunits might suggest that the oligomeric structure of PAF-AH is different from tissue to tissue.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗