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T Tsuzuki

Publications and source records attributed to T Tsuzuki.

At least 91 records · Page 5Linked to original sources
PubMed1996

Targeted disruption of the DNA repair methyltransferase gene renders mice hypersensitive to alkylating agent.

Alkylation of DNA at the O(6)-position of guanine is one of the most critical events leading to induction of mutation as well as to cancer. The enzyme O(6)-methylguanine-DNA methyltransferase repairs this and related lesions in DNA. By means of gene targeting, we established mouse lines deficient in the methyltransferase gene and tissues from these mice contained no methyltransferase activity. Administration of methylnitrosourea to these gene-targeted mice led to early death, and normal mice treated in the same manner showed no untoward effects. In mice given methylnitrosourea treatment, the bone marrow became hypocellular and there was a drastic decrease in the number of leukocytes and platelets, thereby indicating an impaired reproductive capacity of hematopoietic stem cells. Methyltransferase apparently protected these mice from the pancytopenia caused by the alkylating agent.

Alkylating Agents↗
PubMed1996

A prospective randomized trial of the preventive effect of pre-operative transcatheter arterial embolization against recurrence of hepatocellular carcinoma.

To clarify whether pre-operative transcatheter arterial embolization (TAE) improves survival after hepatectomy, a prospective randomized comparative study was done. Of a total of 115 registered patients having solitary hepatocellular carcinoma (HCC) 2 to 5 cm in diameter, 18 (15.7%) were excluded after randomization. As a result, 97 patients were chosen as subjects and divided into two groups: hepatectomy with (group A: n=50) and without (group B: n=47) pre-operative TAE. The period of observation of the patients who survived the surgery was between 4.0 and 6.6 years. The randomization appeared to have provided well-balanced groups of patients and the clinico-pathological characteristics of the two groups were quite similar. The necrotic part of the cancerous lesions, as confirmed by operative specimens, amounted to 74.8+/-33.4% (mean +/-SD) in group A and 6.8+/-7.2% in group B (P<0.01). However, the cancer-free survival rates after hepatectomy in both groups showed little difference (39.1+/-7.0 (%+/-SE) and 31.1+/-0.1, respectively). We speculate that TAE is not effective against such HCC accessory lesions as minute intrahepatic metastasis and tumor thrombus and that pre-operative TAE does not improve post-operative survival.

Adult↗
PubMed1996

Primary adenocarcinoma of the renal pelvis with special reference to histochemical observations.

A case of adenocarcinoma of the renal pelvis is presented. The patient was an 84-year-old man suffering from long-standing right-sided nephrolithiasis. Surgical resection of the right kidney revealed adenocarcinoma with slight stromal invasion. A tubulovillous adenoma, which was morphologically similar to an adenoma of the large intestine, was also found adjacent to the adenocarcinoma. The pelvic epithelium neighboring the lesion revealed intestinal metaplasia. Histochemical studies revealed that the tumor in the patient and adenocarcinomas or adenomas of the large intestine have similar properties of cytoplasmic mucin. These findings suggest that the epithelium with intestinal metaplasia may have developed into the adenoma and finally transformed into the adenocarcinoma. In addition, only tumor cells with severe atypia, most of which morphologically corresponded to adenocarcinoma, demonstrated positive nuclear staining for anti-p53. This suggests that p53 may play an important role in the malignant transformation of adenomas into adenocarcinomas, as is the case in the large intestine.

Adenocarcinoma↗
PubMed1996

Alterations of p16/CDKN2, p53 and ras genes in oral squamous cell carcinomas and premalignant lesions.

Exons 1-3 of the p16/CDKN2 gene, exons 4-9 of the p53 gene and exons 1 and 2 of H-, K- and N-ras genes were screened for mutations by a combination of immunohistochemistry and single-strand conformational polymorphism (SSCP) analyses of polymerase chain reaction products from human surgical samples of both frank oral squamous cell carcinomas and premalignant lesions. The samples included 20 squamous cell carcinomas, 10 epithelial dysplasias and 10 epithelial hyperplasias. No identifiable gene mutations were detected in any of the dysplasias or hyperplasias, while 2 (10%) deletions and 2 (10%) mutations of p16/CDKN2, along with 5 (25%) p53 mutations were found in the advanced carcinomas, yielding characteristic p16/ CDKN2 and p53 changes. A mutation in the K-ras gene was found in single carcinoma and dysplastic samples. From the data, it can be argued that p16/CDKN2 and p53 mutations are relatively late occurrences in human oral tumorigenesis and that genetic alterations of the ras genes may not play a significant role in squamous neoplasia.

Carcinoma, Squamous Cell↗
PubMed1996

Tumor cell proliferation and apoptosis associated with the Gamma Knife effect.

In this study, the expression of proliferating-cell nuclear antigen (PCNA) and Bcl-2 protein was examined in neurinomas, meningiomas, pituitary adenomas, and malignant lymphomas before treatment with Gamma Knife radiosurgery. Tumor volume was rapidly reduced by radiosurgery in all malignant lymphomas and in some benign tumors. The latter had been characterized by strong positive immunohistochemical staining for PCNA and Bcl-2. Radiation-induced apoptosis is thought to contribute to the low-dose effects of Gamma Knife radiosurgery. A population with a large proportion of proliferating cells may be susceptible to the induction of apoptosis, and the presence of Bcl-2 may not suppress this Gamma Knife effect.

Apoptosis↗
PubMed1996

Irradiation effects on the metabolism of metastatic brain tumors: analysis by positron emission tomography and 1H-magnetic resonance spectroscopy.

To evaluate irradiation effects on the metabolism of metastatic brain tumors treated by Gamma Knife radiosurgery, positron emission tomography (PET) and 1H-magnetic resonance spectroscopy (MRS) studies were performed on five patients. The tumor origins were lung cancer in three patients and breast cancer in two. Treatment volume was 0.4-10.1 cm3 (mean: 5.5 cm3). The marginal dose to the tumor was 24-30 Gy (mean: 26.2 Gy). The follow-up period was 5-19 months (mean: 13.4 months). No patients had conventional whole-brain radiation therapy. 18F-fluoroboronophenylalanine (18FBPA) or 18F-fluorodeoxyglucose (18FDG) were used as tracers for the PET study. Using 1H-MRS, several metabolites were simultaneously measured in metastatic brain tumor and adjacent brain. In the PET study of the representative case, the uptake rate of 18FBPA that is actively transported to the tumor decreased markedly 15 days after radiosurgery and continued to decrease thereafter. In the 1H-MRS study, choline, which is characteristically high in metastatic brain tumors, also decreased over time. In two cases with suspected radiation injury, the enhanced region, which was decreased in size in early follow-up, enlarged progressively and was accompanied by edema. However, 18FBPA and 18FDG were not transported to the enhanced region. The peak of free lipid, which might show destruction of the cell membrane, was recognized in the enhanced region and adjacent brain in these cases. This study revealed that radiation effects on the metabolism of metastatic brain tumors occur at an early stage after radiosurgery and continue over several months. In particular, in the case of radiation injury, PET and 1H-MRS studies made it possible to distinguish between regrowth of the tumor and radiation injury.

Aged↗
PubMed1996

Primary cardiac lymphoma. No evidence for an etiologic association with Epstein-Barr virus.

OBJECTIVES: To report two cases of primary cardiac lymphoma, a rare extranodal lymphoma with an unknown pathogenesis, and to compare them to secondary B-cell cardiac lymphoma. DESIGN: Clinicopathologic features are described, using histologic and immunophenotypic examinations. The Epstein-Barr virus genome is detected by in situ hybridization. PATIENTS: Of 80 autopsied cases of malignant lymphoma identified at Nagoya (Japan) University Hospital, two patients with primary cardiac lymphoma and five patients with secondary cardiac B-cell lymphoma were selected. RESULTS: None of the seven selected cases showed immunodeficiency, autoimmune disorders, or chronic inflammatory processes. Primary cardiac lymphomas had B-cell phenotypes with mu and lambda chain monoclonality. Immunostaining for Epstein-Barr virus (latent membrane protein-1) and Epstein-Barr virus-encoded RNA-1 in situ hybridization did not demonstrate an association of these lymphoma with Epstein-Barr virus infection. The majority of secondary cardiac B-cell lymphomas were extranodal lymphomas and extranodal or serosal involvement was more prominent than nodal involvement. CONCLUSION: These findings suggest that primary cardiac lymphoma, unlike pyothorax-associated pleural lymphoma, appears to have no association with chronic inflammation or Epstein-Barr virus infection.

Aged↗
PubMed1996

[Nine cases of spontaneous hemopneumothorax with massive bleeding].

We experienced nine cases of spontaneous hemopneumothorax. All the patients were male and six of those had received emergent operations because of massive intrathoracic bleeding. In six of the nine cases we found the bleeding from the ruptured string like tissues between parietal pleura and the apex of the upper lobe. Those string like tissues contained vessels and were suspected to have ruptured when the lung collapsed. In other three cases the bleeding was controlled conservatively but operations were performed because of continuous air leakage and the bleeding were found from the bullous apical tissues of the lung adhered to the thoracic wall. Histopathologically those bullous tissues and string like tissues were revealed grannuromatous and chronic pleuritis rich in microvessels. Early thoracotomy for spontaneous hemopneumothorax was recommended in case of massive intrathoracic bleeding.

Adult↗
PubMed1996

[A case of bronchogenic cyst in the subdiaphragmatic region].

A 62-year-old male who had gallbladder stone was admitted because of an abnormality in abdominal CT. Abdominal CT revealed the mass lesion with smooth margin under the diaphragmatic area, whose density was higher than that of water. Both MRI T1-weighted and T2-weighted images showed a relatively high intensity. On ultrasonography, the lesion was consisted of a thin wall. On the basis of these imaging modalities, the diagnosis was considered to be cyst. The mass was resected via posterior extraperitoneal approach, and its histologic diagnosis was bronchogenic cyst containing turbid fluid. Subdiaphragmatic bronchogenic cyst is rarely reported. The characteristic findings of MRI and ultrasonography was useful for the diagnosis of a cyst with turbid contents.

Bronchogenic Cyst↗
PubMed1995

Mouse MTH1 protein with 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphatase activity that prevents transversion mutation. cDNA cloning and tissue distribution.

8-Oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) is formed in the nucleotide pool of a cell during normal cellular metabolism, and when it is incorporated into DNA causes mutation. Organisms possess 8-oxo-dGTPase, an enzyme that specifically degrades 8-oxo-dGTP to 8-oxo-dGMP. We isolated cDNA for mouse 8-oxo-dGTPase, using as a probe human MTH1 (Escherichia coli mutT homolog) cDNA. The nucleotide sequence of the cDNA revealed that the mouse MTH1 protein (molecular weight of 17,896) comprises 156 amino acid residues. When the cDNA for mouse 8-oxo-dGTPase was expressed in E. coli mutT- mutant cells devoid of their own 8-oxo-dGTPase activity, an 18-kDa protein, which is cross-reactive with an anti-human MTH1 antibody, was formed. In such cells, the level of spontaneous mutation frequency that was elevated reverted to normal. High levels of 8-oxo-dGTPase activity were found in liver, thymus, and large intestine, whereas all other organs examined contained smaller amounts of the enzyme. In embryonic stem cells, an exceedingly high level of the enzyme was present.

Amino Acid Sequence↗
PubMed1995

Serum pyridinolines as specific markers of bone resorption in hemodialyzed patients.

Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline were quantified in uremic patients undergoing maintenance hemodialysis and in healthy subjects. Pre-hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline in the hemodialyzed patients were significantly higher than those in healthy subjects. Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline decreased significantly after hemodialysis with reduction rates of about 40%. Pre-hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline correlated significantly with intact parathyroid hormone, osteocalcin and bone-specific alkaline phosphatase. Lysyl pyridinoline showed better correlations with these parameters than hydroxylysyl pyridinoline. Parathyroidectomy markedly decreased serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline. These results indicate that serum pyridinolines, especially lysyl pyridinoline, may be used as specific biochemical markers of bone resorption in hemodialyzed patients.

Acid Phosphatase↗
PubMed1995

Spatial and temporal expression of the ret proto-oncogene product in embryonic, infant and adult rat tissues.

Immunohistochemical analysis with the anti-Ret antibody was performed to investigate the expression of the c-ret proto-oncogene product (c-Ret protein) in embryonic, infant and adult rat tissues. During embryogenesis, the c-Ret expression became detectable by day 11.5 in the developing peripheral and central nervous systems as well as in the excretory system. In the peripheral nervous system of the trunk, it was expressed at high levels in the enteric neuroblasts and the autonomic and dorsal root ganglia. c-Ret positive cells appeared in the mesenchyme around the foregut and the dorsal aorta at day 11.5 and formed the myenteric plexus of the whole embryonic gut and the sympathetic trunk at later stages respectively. Examination of the cranial region revealed that the c-Ret protein was expressed in neural crest cells migrating from rhombomere 4 at day 11.5 and then became positive in the facial, glossopharyngeal and vagus cranial ganglia at day 12.5-13.5. After day 16.5 of gestation, the c-Ret expression was also observed in the trigeminal ganglion. In the central nervous system, the c-Ret protein was expressed in the neuroepithelial cells of the ventral neural tube (day 11.5-14.5), the motor neurons of the spinal cord (day 18.5) as well as in the embryonic neuroretina (day 18.5). In addition to the nervous system, the c-Ret expression was detected in the nephric duct (day 11.5), the ureteric bud (day 13.5) and the collecting ducts of the kidney (day 16.5). After birth, neurons in the nervous systems mentioned above continued to express the c-Ret protein at variable levels while no c-Ret expression was observed in the kidney of adult rats. Furthermore, the c-Ret expression was found in the acinar cells of the salivary gland, the epithelial cells of the thymus and the follicular dendritic cells of the spleen and lymph node in infant and adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation.

hoxb-5 and hoxb-6 are adjacent genes in the mouse HoxB locus and are members of the homeotic transcription factor complex that governs establishment of the mammalian body plan. To determine the roles of these genes during development, we generated mice with a targeted disruption in each gene. Three phenotypes affecting brachiocervicothoracic structures were found in the mutant mice. First, hoxb-5- homozygotes have a rostral shift of the shoulder girdle, analogous to what is seen in the human Sprengel anomaly. This suggests a role for hoxb-5 in specifying the position of limbs along the anteroposterior axis of the vertebrate body. Second, hoxb-6- homozygotes frequently have a missing first rib and a bifid second rib. The third phenotype, an anteriorizing homeotic transformation of the cervicothoracic vertebrae from C6 through T1, is common to both hoxb-5- and hoxb-6- homozygotes. Quite unexpectedly, hoxb-5, hoxb-6 transheterozygotes (hoxb-5-hoxb-6+/hoxb-5+ hoxb-6-) also show the third phenotype. By this classical genetic complementation test, these two mutations appear as alleles of the same gene. This phenomenon is termed nonallelic noncomplementation and suggests that these two genes function together to specify this region of the mammalian vertebral column.

Alleles↗
PubMed1995

Host intestinal intraepithelial gamma delta T lymphocytes present during acute graft-versus-host disease in mice may contribute to the development of enteropathy.

We reported that T cell receptor (TcR) gamma delta intestinal intraepithelial lymphocytes (i-IEL) of host origin increased transiently, then decreased drastically at the early stage of non-irradiated acute graft-versus-host disease (GVHD) in mice. We investigated the role of the TcR gamma delta i-IEL of host origin in the pathogenesis of the intestinal lesions that occur during acute GVHD. The acute GVHD was induced in mice which had been depleted of TcR gamma delta by in vivo administration of hamster monoclonal antibody (mAb) against TcR gamma delta. Although the degree of splenomegaly after the induction of acute GVHD in mice treated with anti-TcR gamma delta mAb was similar to that in control mice treated with hamster anti-2,4,6-trinitrophenyl mAb, infiltration of donor-derived T cells into the epithelium, and mitosis and apoptosis of crypt cells in the intestinal mucosa were dramatically suppressed in these mice. This suggest that host TcR gamma delta T cells in i-IEL contribute to the development of enteropathy in acute GVHD in mice.

Animals↗
PubMed1995

cDNA and genomic sequences for rat 8-oxo-dGTPase that prevents occurrence of spontaneous mutations due to oxidation of guanine nucleotides.

The enzyme, 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase), is present in various organisms and plays an important role in control of spontaneous mutagenesis. This enzyme degrades 8-oxoguanine-containing deoxyribonucleoside triphosphate, a potentially mutagenic substrate for DNA synthesis, to the corresponding monophosphate. To obtain appropriate probes for expression of the gene in various tissues and also to construct appropriate experimental models for carcinogenesis, we cloned cDNA for rat 8-oxo-dGTPase and elucidated its structure. The nucleotide sequence of the cDNA revealed that the rat 8-oxo-dGTPase protein is composed of 156 amino acid residues. The molecular weight of rat 8-oxo-dGTPase, calculated from the predicted amino acid sequence, was 18,006, and the 8-oxo-dGTPase protein of this size was detected when the cDNA was expressed in 8-oxo-dGTPase-deficient Escherichia coli mutT- cells. The predicted amino acid sequence of the rat 8-oxo-dGTPase has a close homology with those of human and bacterial counterparts. Using the cDNA as a probe, part of the rat gene for 8-oxo-dGTPase was isolated and was found to consist of at least three exons and spanned about 10 kb. A genomic region containing the pseudogene was also isolated.

Amino Acid Sequence↗
PubMed1995

p53 mutations occur in clinical, but not latent, human prostate carcinoma.

To elucidate the role of the p53 tumor suppressor gene in prostate tumorigenesis, we probed for mutations in latent and clinical prostate cancers using single strand conformation polymorphism (SSCP) and restriction fragment length polymorphism (RFLP) analysis in combination with direct gene sequencing and immunohistochemical methodologies. Fifteen cases of subclinical and 32 cases of clinical carcinoma, the latter graded in stages A through D, were available for study. While p53 point mutations were detected in only 5 of 32 (16%) clinical cancers, no mutations were detected in latent disease. Of the carcinomas in stages B, C and D, 15% (2/13), 29% (2/7) and 9% (1/11) were positive for p53 mutations, respectively. Although no specific mutational patterns were observed, the aberrations found were predominantly single base missense substitutions. The data suggest not only an association of p53 mutation and progression of clinical prostate cancer, but also imply that some other mechanism(s) are at work in latent carcinoma.

Base Sequence↗