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Biomedical subjects

M Katoh

Publications and source records attributed to M Katoh.

At least 109 records · Page 6Linked to original sources

Recurrence of giant adrenocortical carcinoma in the contralateral adrenal gland 6 years after surgery: report of a case.

We report herein the case of a patient in whom a giant adrenocortical carcinoma was found to have recurred in the contralateral adrenal gland and intrapelvic cavity 6 years after his initial operation. A 52-year-old man had consulted our hospital complaining of right upper abdominal pain and weight loss, and was subsequently diagnosed as having a giant adrenal tumor by computed tomography scans and echography. A laparotomy was performed and the tumor, located in the right retroperitoneal cavity and infiltrating the liver and right kidney, was surgically removed. The lesion, 29 x 19 x 10 cm in size and 4700 g in weight, was histopathologically diagnosed as an adrenocortical carcinoma. Adjuvant chemotherapy with mitotane was given for 3 months and his postoperative course was uneventful until a recurrence in the contralateral adrenal gland and peritoneal cavity was found 6 years later. The second resection was successful, and he is currently alive with no further sign of recurrence 8 years after his first operation. We report this unusual case as it provides much useful information on the biological features of adrenocortical carcinomas and the state of tumor dormancy.

Adrenal Cortex Neoplasms↗

Rapid growth of a retroperitoneal rhabdomyosarcoma following right hemicolectomy for ascending colon cancer: report of a case.

We report herein the case of a 69-year-old man in whom rapid growth of a retroperitoneal rhabdomyosarcoma occurred following hemicolectomy for ascending colon cancer. On his first admission for surgery, a small lesion, 1.5 cm in diameter, was detected adjacent to the inner side of the left kidney by abdominal axial computed tomography (CT), which was initially suspected to be a benign lesion; however, a postoperative follow-up CT scan done 5 months later revealed that the lesion had enlarged remarkably to 8 cm in diameter. Thus, total resection was performed under the presumed diagnosis of a malignant retroperitoneal tumor. The tumor was found to be adjacent to the inner portion of the left kidney and covered by Gerota's fascia. As it involved the ileolumbar muscle and had a metastatic lymph node, complete resection was performed. The resected specimen was 8.5 x 6.5 x 5 cm in size and was histologically confirmed as a retroperitoneal rhabdomyosarcoma of embryonal type. Two courses of adjuvant chemotherapy with adriamycin, vincristine, and cyclophosphamide were given, and the patient has shown no signs of recurrence for 2 years since his second operation.

Adenocarcinoma↗

Inhibitory potencies of 1,4-dihydropyridine calcium antagonists to P-glycoprotein-mediated transport: comparison with the effects on CYP3A4.

PURPOSE: Recently, we clarified the inhibitory effects of 13 kinds of 1,4-dihydropyridine calcium antagonists on human cytochrome P450 (CYP) 3A4. It has been reported that the substrates and/or inhibitors are overlapped between CYP3A4 and P-glycoprotein (P-gp). The purpose of this study was to investigate the inhibitory effects of 13 kinds of 1,4-dihydropyridine calcium antagonists on P-gp-mediated transport in order to evaluate the overlapping specificity of the inhibitors between P-gp and CYP3A4. METHODS: The transcellular transports of [3H]daunorubicin or [3H]digoxin by monolayers of LLC-GA5-COL150 cells in which P-gp was overexpressed were measured in the presence or absence of the 1,4-dihydropyridine calcium antagonists. RESULTS: The transport of [3H]daunorubicin was strongly inhibited by manidipine, barnidipine, benidipine, (-)-efonidipine, nicardipine, (+)-efonidipine, and amlodipine with the IC50 values of 4.6, 8.6, 9.5, 17.3, 17.5, 20.6, and 22.0 microM, respectively. The transport of [3H]digoxin was strongly inhibited by benidipine, nicardipine, barnidipine, and manidipine. CONCLUSIONS: It was clarified that 13 kinds of 1,4-dihydropyridine calcium antagonists have different inhibitory potencies and substrate specificities to the transport of [3H]daunorubicin or [3H]digoxin. Some compounds did not demonstrate the overlapping specificity for inhibition between P-gp and CYP3A4. It was also clarified that nicardipine, benidipine, manidipine, and barnidipine were strong inhibitors of P-gp as well as CYP3A4.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Stability of transferred human chromosome fragments in cultured cells and in mice.

Chromosome fragments represent feasible gene delivery vectors with the use of microcell-mediated chromosome transfer. To test a prerequisite for a gene delivery vector, we examined the stability of human chromosome fragments (hCFs) in cultured cells and in trans-chromosomic (Tc) mice. Fragments of human chromosomes 2 (hCF(2-W23)), 11 (hCF-11) and 14 (hCF(SC20)) tagged with neo were introduced into the TT2F mouse ES cells, and retention of the hCFs was examined by FISH during long-term culture without selection. In contrast to the gradual loss of hCF(2-W23) and hCF-11, hCF(SC20) remained stable over 70 population doublings in the ES cells. The hCF(SC20) was also stable in cultured human tumor cells and chicken DT40 cells. We have previously generated chimeric mice using the ES cells harboring the hCF(2-W23) or hCF(SC20), followed by production of Tc mice. Although both the hCF(2-W23) and hCF(SC20) persisted in cells of Tc mice as an additional chromosome and were transmitted to offspring, the hCF(SC20) was more stable than the hCF(2-W23) in F1 and F2 mice. The present study shows that the stability of hCFs in Tc mice differs with tissue types and with genetic background used for successive breedings. Thus, the hCF(SC20), which was relatively stable in both mouse and human cells, may be a promising candidate for development as a gene delivery vector.

Animals↗

Liposome-encapsulated OK-432 specifically and sustainedly induces hepatic natural killer cells and intermediate T cell receptor cells.

BACKGROUND: OK-432 is a biological response modifier used in Japan to augment host immunity and is known to increase the host antitumour response. By using liposomes, which are vesicles made from phospholipids that have a structure resembling the cell membrane, we encapsulated OK-432. METHODS AND RESULTS: Encapsulated OK-432 was injected into the tail veins of mice, and its effect was compared with that of unencapsulated OK-432 given intravenously. In mice that received either form of OK-432, both the number of natural killer (NK) and intermediate T cell receptor (intTCR) cells (intrahepatic T cells generated by extrathymic differentiation) increased markedly in the liver, with the peak level occurring 3 days after administration. Both forms of OK-432 also increased cytotoxic activity against Yac-1 cells. The increase in numbers of cells and in cytotoxic activity in the liver persisted for longer in mice that received encapsulated OK-432 than in animals that received unencapsulated OK-432. CONCLUSIONS: Because it has been shown that both NK and intTCR cells play an important role in tumour immunity, an increase in the number of such cells can be considered likely to have an increased antitumour effect. Encapsulated OK-432 elicited liver-specific augmentation of cytotoxic activity and the effect was more persistent than that produced by OK-432 given in the conventional form; therefore, it may be useful for the treatment of tumours, particularly those arising in the liver.

Animals↗

Asymptomatic schwannoma of the oculomotor nerve: case report.

Intracranial oculomotor schwannoma without neurofibromatosis is rare and is usually symptomatic. Only one case of asymptomatic oculomotor schwannoma has been previously reported. We present a case of intracranial oculomotor schwannoma which caused no signs or symptoms. Microsurgical resection of this tumour resulted in oculomotor palsy. We reviewed 7 reported cases and the findings indicated that radical removal of the tumour invariably caused or worsened the oculomotor palsy. The reason why the tumour caused no symptoms in this case was unclear. However, improvements in diagnostic methods such as magnetic resonance imaging (MRI) may increase the detection of such asymptomatic cases. Indications for surgical treatment should be established.

Aged↗

Bilateral medial medullary infarction.

We present a case of bilateral medial medullary infarction demonstrated by magnetic resonance imaging (MRI) and review 12 previously reported cases. We classify these 13 cases (including the present case) into two groups according to the extent of the ischemic region: type 1, the ischemic lesion developed from the medullary pyramid to the medial longitudinal fasciculus; type 2, the lesion was confined to the medullary pyramid.A 71 year old man presented with slight disturbance of consciousness, dysarthria, disturbance of leftward gaze, no gag reflex and tetraparesis. He developed nearly complete horizontal ophthalmoplegia. MRI revealed upper medial medullary infarction bilaterally that extended to the pontomedullary junction. We propose that the prognosis of type 2 bilateral medial medullary infarction is better than that of type 1. Furthermore, the prognosis of bilateral medial medullary infarction itself may be better than previously indicated.

Aged↗

Differential effects of imidapril and candesartan cilexetil on plasminogen activator inhibitor-1 expression induced by prolonged inhibition of nitric oxide synthesis in rat hearts.

We investigated effects of the angiotensin-converting enzyme (ACE) inhibitor imidapril and the angiotensin II type 1 (AT1) antagonist candesartan cilexetil on cardiac plasminogen activator inhibitor-1 (PAI-1) expression in rats. Cardiac PAI-1 mRNA levels were increased after a 7-day treatment with the nitric oxide (NO) synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). PAI-1 immunoreactivity was increased in the coronary arteries. Treatment with imidapril significantly prevented the L-NAME-induced increase in the gene expression and immunoreactivity of PAI-1, but candesartan cilexetil showed no such effect. This study provides the first evidence of differential effects of ACE inhibition and AT1 antagonism on cardiac PAI-1 expression in vivo.

Actins↗

[Research and development of novel modified tissue-type plasminogen activator (t-PA), pamiteplase].

Tissue-type plasminogen activator (t-PA) is a potent thrombolytic agent that, owing to its strict fibrin specificity, is superior to urokinase and streptekinase. However, due to its extremely short half life (approximately 5 min), it is necessary to administer this drug by high-dosage infusion, increasing the possibility of systemic bleeding. We therefore considered it clinically desirable to create a thrombolytic agent with a prolonged plasma half life that can be administered by bolus injection. To this end, we created several genetically modified t-PA analogues and screened them for thrombolytic activity and in vivo pharmacokinetics. Of these, Pamiteplase (YM866) showed an improved plasma clearance profile without a reduction in fibrinolytic potency and fibrin specificity. In clinical studies on acute myocardial infarction (AMI), patients were injected with bolus Pamiteplase intravenously at dosages of 0.05, 0.1, or 0.2 mg/kg-body weight. Angiographical examination of coronary artery showed that high incidence (70-76%) of reperfusion evaluated as TIMI grade II or III was achieved by the injection of 0.1 or 0.2 mg/kg of Pamiteplase. No anti-Pamiteplase antibodies have thus far been detected in the blood of patients. From these results, we conclude that it is of great clinical significance that Pamiteplase can be administered by single bolus injection to AMI patients.

Animals↗

Intrapleural administration of a large amount of diluted fibrin glue for intractable pneumothorax.

OBJECTIVE: Pleurodesis using chemical agents has been applied to high-risk patients with pneumothorax. This treatment, however, is sometimes unsuccessful in patients with intractable pneumothorax or intrapleural dead space. We developed a technique for the intrapleural administration of diluted fibrin glue as a treatment for such patients. METHODS: Fibrin glue was diluted fourfold with saline solution and/or contrast medium. Pleurodesis with a large amount of the diluted fibrin glue was performed in 40 high-risk patients with intractable pneumothorax and in 13 postthoracotomy patients with persistent air leakage associated with an intrapleural dead space. RESULTS: The air leaks were stopped by administration of the glue in all patients of both groups. During the follow-up period, a recurrence rate of 12.5% was observed in the former group. These recurrent pneumothoraces also were successfully treated by glue administration with no further recurrence. In the 13 postthoracotomy patients, there was no recurrence after the initial treatment. Pyrexia (12.5%) and chest discomfort (4.1%) were observed as side effects, but there were no findings of severe chest pain or thoracic empyema. CONCLUSIONS: These results suggest that intrapleural administration of a large amount of diluted fibrin glue is a useful treatment for intractable pneumothoraces in high-risk or postthoracotomy patients who have an intrapleural dead space.

Adult↗

Bactericidal activity of a monoclonal antibody against a recombinant 40-kDa outer membrane protein of Porphyromonas gingivalis.

BACKGROUND: We have cloned the gene for a 40-kDa outer membrane protein (40-kDa OMP) from Porphyromonas gingivalis 381. The recombinant (r)40-kDa OMP has become the subject of considerable interest because of its potential role in the development of a vaccine useful for passive immunization. To develop such a vaccine, it is essential to fully understand the functions of anti-r40-kDa OMP antibody in the host defense against P. gingivalis. To that end, we developed a panel of monoclonal antibodies by immunizing mice with purified r40-kDa OMP. The objective of this study was to determine the bactericidal activity on P. gingivalis by the IgG1 monoclonal antibody Pg-ompA2. METHODS: Bacterial growth measurement, a complement-mediated anti-P. gingivalis assay based on [3H]thymidine uptake, and a 14C-release assay were performed to test the bactericidal activity of Pg-ompA2 to P. gingivalis. RESULTS: In the presence of complement, Pg-ompA2 was lethal to P. gingivalis 381 as well as to the more virulent P. gingivalis strains, including ATCC 53977 and W83. Using component-deficient complement, we determined that Pg-ompA2 killed P. gingivalis by activating both the classical and alternative complement pathways. CONCLUSIONS: Pg-ompA2 has an in vitro complement-mediated bactericidal activity to P. gingivalis. Pg-ompA2 may contribute to the development of a local immunotherapy that can be applied in the gingival crevice of a patient with P. gingivalis-related periodontitis, or be a vaccine candidate.

Animals↗

Postmortem findings in two familial amyloidosis patients with transthyretin variant Asp38Ala.

Postmortem findings in 2 familial amyloidosis patients with the transthyretin variant (ATTR), Asp38Ala, are described Both showed cardiac failure, and progressive peripheral and autonomic neuropathy and died at the ages 82 and 57, respectively. TTR immunoreactive amyloid deposition was observed to be extensive in the myocardium, peripheral nerves, sympathetic ganglia and gastrointestinal tract. The pulmonary parenchyma was also diffusely involved, but renal glomeruli, follicular tissues of the thyroid, and the leptomeninges and subarachnoidal vessels of the central nervous system showed little deposition. The latter findings are not usually seen in the patients with ATTR Val30Met, the most common form of familial amyloidosis. Additionally, the clinicopathological findings of familial amyloidosis with ATTR Asp38Ala seem to vary in the different individuals.

Aged↗

Two types of aggregate in the cerebral cortex of a seizure-sensitive strain of the Mongolian gerbil.

A 70-kDa protein, P70, found mostly in the pyramidal cells of the cerebral cortex of cobalt-induced epileptogenic rats, has been implicated in epileptogenesis. The presence of a P70-like substance was searched for immunohistochemically in the cerebral cortex of MGS/ldr, a seizure-sensitive strain of the Mongolian gerbil (Meriones unguiculatus) that we previously established. Immunoreactive aggregates were observed in the pyramidal neurons of the motor cortex and the primary somatosensory cortex. Analysis using confocal laser scanning microscopy revealed that the aggregates were often colocalized with a second type of aggregate with red autofluorescence at the marginal zone of the cell somata. Both aggregates appeared and increased before the appearance of generalized tonic-clonic convulsion. These may be involved in some change of physiological function of the cerebral cortex but their presence itself is not enough to determine the occurrence of epileptic seizure because the gerbils that showed no such seizure had both aggregates.

Animals↗

Molecular cloning and characterization of human Frizzled-4 on chromosome 11q14-q21.

The WNT receptors, encoded by the Frizzled genes, are implicated in a variety of cellular processes such as cell fate determination, cell polarity control, and malignant transformation. Human Frizzled-4 (FZD4) cDNAs have been cloned and characterized. FZD4 spans a total of 7392 nucleotides and encodes a 537-amino-acid protein with the N-terminal cysteine-rich domain, seven transmembrane domains, and the C-terminal S/T-X-V motif. The FZD4 mRNA of 7.7 kb in size were detected almost ubiquitously in normal human tissues and larger amounts in fetal kidney, adult heart, skeletal muscle, and ovary. Among cancer cell lines, the FZD4 mRNA level was higher in HeLa S3. The FZD4 gene has been mapped to human chromosome 11q14-q21. FZD4 is homologous to FZD9 and FZD10, and overall amino acid identity is as follows: FZD4 vs FZD9, 51.6%; FZD4 vs FZD10, 51.2%; FZD9 vs FZD10, 65.7%. FZD4 consists of two exons, while FZD9 and FZD10 consist of a single exon. FZD4 might belong to rather the independent FZD subfamily than the FZD9-FZD10 subfamily.

Adult↗

Telomerase activity correlates with histo-pathological factors in uterine endometrial carcinoma.

Telomerase activity has been implicated in the progression of various human tumors. Our aim was to evaluate telomerase activity and to compare it with histo-pathological factors in uterine endometrial carcinoma, to look for possible correlations. Telomerase activity was measured by dilution analysis using a PCR-based telomeric repeat amplification method and detected in 31 of 35 primary endometrial carcinoma tumor specimens. High telomerase activity, detected after 100-fold dilution of extracts, was identified in 15 specimens. There was no significant correlation between the positive telomerase activity and tumor surgical stage or histo-pathological factors. However, high telomerase activity was significantly correlated with advanced surgical stage and with pelvic lymph node metastasis. Our findings suggest that an increase in telomerase activity may be associated with tumor progression and that its level may have a prognostic value in endometrial carcinoma.

Adult↗