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Biomedical subjects

S Hatakeyama

Publications and source records attributed to S Hatakeyama.

At least 109 records · Page 6Linked to original sources

Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases.

In most instances, the transfer of ubiquitin to target proteins is catalyzed by the action of ubiquitin protein ligases (E3s). Full-length cDNAs encoding murine E6-associated protein (mE6-AP) as well as Nedd-4, a protein that is homologous to E6-AP in its C terminus, were cloned. Nedd-4 and mouse E6-AP are both enzymatically active E3s and function with members of the UbcH5 family of E2s. Mouse E6-AP, like its human counterpart, ubiquitinates p53 in the presence of human papilloma virus E6 protein, while Nedd-4 does not. Consistent with its role in p53 ubiquitination, mE6-AP was found both in the nucleus and cytosol, while Nedd-4 was found only in the cytosol. Binding studies implicate a 150-amino acid region that is 40% identical between mE6-AP and Nedd-4 as a binding site for the C-terminal portion of an E2 enzyme (UbcH5B). Nedd-4 was determined to have a second nonoverlapping E2 binding site that recognizes the first 67 amino acids of UbcH5B but not the more C-terminal portion of this E2. These findings provide the first demonstration of physical interactions between mammalian E2s and E3s and establish that these interactions occur independently of ubiquitin and an intact E3 catalytic domain. Furthermore, the presence of two E2 binding sites within Nedd-4 suggests models for ubiquitination involving multiple E2 enzymes associated with E3s.

Amino Acid Sequence↗

Csk overexpression reduces several monokines and nitric oxide productions but enhances prostaglandin E2 production in response to lipopolysaccharide in the macrophage cell line J774A.1.

The catalytic activity of src-family protein tyrosine kinases (src-PTK) is suppressed when a C-terminal tyrosine is phosphorylated by an intracellular PTK, C-terminal Src kinase (Csk). In the present report, to study the regulatory functions of the Csk in cells of monocyte/macrophage lineage, we transfected a eukaryotic expression vector containing rat csk cDNA in a macrophage cell line, J774A.1, and examined alterations of the response to lipopolysaccharide (LPS) in the transfectants which overexpressed Csk. Csk overexpression resulted primarily in a down-regulation of Fgr activity, an src-PTK expressed in J774A.1, and hyperphosphorylation of several cellular proteins of 35, 57, 66, 97 and 120-130 kDa. Furthermore, in these Csk transfectants, production of interleukin (IL)-1alpha, IL-6, tumor necrosis factor-alpha, and nitric oxide (NO) following LPS stimulation were reduced compared with those in parental J774A.1 or J774A.1 transfected with the vector alone. The extent of reduction paralleled the amounts of Csk proteins expressed in the Csk-transfected J774A.1. The reduced NO production in these cells was associated with low levels of mRNA of inducible NO synthetase. On the other hand, an enhancement of prostaglandin E2 production was observed in the Csk-transfected J774A.1 cells upon stimulation with LPS, which appeared to result from the high level of prostaglandin-H synthetase in the transfectants. The present findings indicate that overexpression of Csk has differential effects on the regulation of production of chemical mediators and monokines, probably via modulation of signal transduction downstream of LPS-mediated signals.

Animals↗

Correlation between overall pesticide effects monitored by shrimp mortality test and change in macrobenthic fauna in a river.

The relationship between change in benthic fauna in the Suna River and shrimp mortality in the river water samples (test was conducted two times per week from May to September) was investigated to assess the insecticide impact on the benthic community. The river was selected because pesticide application had been restricted for a long time in the upper reaches, while aerial insecticide spraying had been done four times on paddy fields in the lower reaches in summer. Species richness and density of benthos were high at the stations in the upper reaches. High shrimp mortality was measured in the water samples collected from a downstream station during the pesticide spraying period, from late July to late August. Species richness and density of benthos markedly decreased at the stations in the lower reaches in that period. However, several species of chironomids, Cheumatopsyche (Trichoptera), which demonstrated tremendous insecticide resistance, and Baetis sahoensis (Ephemeroptera), which has a high recovery potential, were not affected, even in the insecticide spraying period. The benthic fauna in the lower reaches tended to recover from autumn to spring, although not sufficiently. It is considered that the temporal recovery of the benthic community was brought about through recruitment from the benthic community in the 5-km upper reaches. A close correlation was found between the high mortality of shrimp in the water samples and the deterioration in the benthic fauna in this river which was contaminated with insecticides during the summer.

Animals↗

Right hepatectomy for pyogenic liver abscesses with true multiloculation.

We report the case of 61-year-old woman with cryptogenic liver abscesses who had been profoundly ill with severe upper abdominal pain, impaired consciousness, prostration, continuous high fever secondary to sepsis, and thrombocytopenia (platelets, 1-5 x 10(4)/mm3) since admission. Ultrasonograms and computed tomograms revealed two separate multiloculated lesions in the right lobe of the liver, consistent with the liver abscesses. Immediately after diagnosis, percutaneous abscess drainage was performed under ultrasonographic guidance; however, only a small amount of pus was drained, prompting continuous irrigation of the abscess cavity. Four days later, transcatheter hepatic arterial infusion of antibiotics was attempted. However, the abscesses had enlarged and her general condition had worsened. On hospital day 8, she underwent right hepatectomy because the multiloculated lesions were refractory to drainage. The operation was successful in terms of hepatectomy, although she continued to suffer from sepsis, secondary right subphrenic abscess formation, and prolonged thrombocytopenia with associated coagulation disorders for two months. Examination of multiple cross sections of the resected specimen disclosed that the lesions consisted of aggregations of multiple small locules. There was no communication between the locules and there were true septations, rather than multiloculated lesions with pseudoseptations. The patient has been well for 2 years without recurrent abscess of the liver or any infectious disease.

Drainage↗

A peculiar form of multiple cystic dilatation of the intrahepatic biliary system found in a patient with biliary atresia.

The authors report a peculiar form of intrahepatic multiple cysts of the biliary system in a patient with biliary atresia (BA). An 11-year-old girl was admitted to our institution to be investigated for repeated cholangitis occurring after the age of 10 years. She underwent a hepaticojejunostomy, caused by Type I (cyst-type) BA, in the neonatal period. The radiological examination results showed multiple cystic dilatation of the intrahepatic biliary system with a vascular structure protruding into the cyst lumen. Such cystic dilatation with a protruding vascular structure has been noted in patients with Caroli's disease and congenital hepatic fibrosis, and ductal plate malformation is shown to be responsible for the cyst formation. The authors postulate that such malformation of the intrahepatic biliary system is related to the cyst formation in our case.

Bile Ducts, Intrahepatic↗

Long-term outcome of endoscopic balloon dilation in obstructive gastroduodenal Crohn's disease.

BACKGROUND AND STUDY AIMS: Although balloon dilation is widely used in nonmalignant pyloric stenosis, little information is available on either the short-term or long-term results of this type of therapy in patients with obstructive gastroduodenal Crohn's disease. PATIENTS AND METHODS: Five patients with Crohn's disease who had obstructive gastroduodenal lesions were treated using endoscopic balloon dilation. RESULTS: All the initial dilations successfully provided symptomatic relief. However, three of the five patients developed recurrent obstructive symptoms during a mean follow-up period of 4.2 years. Due to symptomatic recurrence, three patients required successive or regularly scheduled repeat balloon dilations, which were successful without any complications, and all of the patients were able to avoid surgical intervention. CONCLUSIONS: These results suggest that over a prolonged period of time, patients who have undergone balloon dilation for obstructive gastroduodenal Crohn's disease have a high rate of recurrence of symptomatic gastric obstruction. However, repeat dilations are successful in continuing to prevent the need for surgery.

Adult↗

Expression of bone morphogenetic proteins of human neoplastic epithelial cells.

Bone morphogenetic proteins (BMPs) are crucial factors of osteogenesis. We investigated the expressions of BMP subtypes in human salivary adenocarcinoma cell line (HSG-S8), tongue squamous cell (HSC-4) and gingival squamous cell (Ca9-22) carcinoma cell lines, gastric poorly differentiated adenocarcinoma cell (MNK45) and signet ring cell (KATOIII) carcinoma cell lines, rectal adenocarcinoma (RCM-1, RCM-2, and RCM-3), and thyroid (8505C) and bladder (T24) carcinoma cell lines by reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR disclosed that BMP-1 was expressed in all cell lines examined, and BMP-2 was amplified in almost all cells except MKN45. Two squamous cell carcinomas, HSC-4 and Ca9-22, and KATOIII expressed only BMP-1 and BMP-2. MKN45 did not express BMP-2, but expressed BMP-7 and weakly BMP-4 and BMP-5. In addition to the expression BMP-7, and HSG-S8 expressed BMP-6. These findings indicated that the neoplastic epithelial cells possessed a rather great potency to express BMP mRNAs. On the other hand, among these carcinoma cells, HSG-S8 solely induced bone in nude mouse tumors, and HSC-4 and KATOIII contained many calcified masses in tumors while the rest did not induce either.

Adenocarcinoma↗

MRI findings in the liver in biliary atresia patients after the Kasai operation.

To evaluate liver function in biliary atresia (BA) patients after the Kasai operation, magnetic resonance imaging (MRI) was carried out 28 times in 19 BA patients. Sixteen of these were divided into three groups on the basis of the serum level of total bilirubin (t-bil), glutamic pyruvic transaminase (GPT) and gamma-glutamyltransferase (gamma-GTP) in the postoperative follow-up period (2-11 years). In group 1 (n = 7) the t-bil was continuously kept under 1 mg/100 ml. In group 2 (n = 4) the t-bil was continuously kept under 1 mg/100 ml, but GPT and gamma-GTP remained high (GPT > 100 IU/liter, gamma-GTP > 200 IU/ liter) for more than 2 years. In group 3 (n = 5) an increase in the t-bil level reappeared (1-2 mg/100 ml; n = 4, > 2 mg/100 ml; n = 1). The differences between MRI finding in the 3 groups, and the correlation between MRI findings and laboratory data (t-bil, cholinesterase; ChE, GPT and gamma-GTP), which were taken around the time of MRI examinations, were studied. The results were as follows: (1) All 19 patients had normal or high signal areas of various sizes on T1 weighted images (WI). (2) Eighteen of 19 patients had high signal areas of various sizes on T2 WI in the portal system areas and/or liver parenchyma, and these areas were enhanced by gadolinium-DTPA in about half of the patients. (3) Ten of 16 patients had atrophic change over one liver lobe. (4) MRI findings for group 1 and the other groups were significantly different, and MRI findings, except for atrophic change, were correlated with the increase or decrease in laboratory data taken around the time of MRI examinations (p < 0.05). These results indicate that a normal or high signal area on T1 WI shows functional tissue, and that a high signal area on T2 WI shows tissue damaged by inflammation and/or progressive fibrosis. MRI is useful for evaluating liver function, especially in terms of morphological features, in BA patients after the Kasai operation, and will be one method for establishing their prognosis.

Alanine Transaminase↗

[Massive hemoptysis in a patient with a tuberculous thoracic aneurysm].

A 91-year-old man with a history of pulmonary tuberculosis 20 years earlier came to our hospital because of hemoptysis in May 1993. A chest X-ray film showed infiltrative shadows in the left first arch of the cardiac silhouette, and sputum cultures were positive for Mycobacterium tuberculosis. Despite treatment with antituberculosis drugs, chest X-ray films revealed gradual progression, and he had occasional hemoptysis. He was admitted because of massive hemoptysis in December 1993 and a computed tomogram of the chest revealed an aneurysm of the descending aorta. Sudden and massive hemoptysis occurred in January 1994. At autopsy, the wall of the aneurysm and the surrounding tissue were found to have histological changes characteristic of tuberculosis. Tuberculous thoracic aneurysms are quite rare, but may develop in patients with tuberculosis in other areas.

Aged↗

[Etoposide-induced pneumonitis].

A 70-year-old man was given a diagnosis of small cell lung cancer because of the findings of examination of a specimen obtained by transbronchial lung biopsy from the rS4 a. He was treated with 2 courses of neoadjuvant chemotherapy (CBDCA, Etoposide) and underwent right middle lobectomy. He was then given 3 courses of adjuvant chemotherapy (CBDCA, Etoposide) as an inpatient and received oral etoposide (50 mg/day) as an outpatient. He was then admitted to our hospital because of dyspnea and fever. A chest-X-ray film showed reticulonodular shadows in both lung fields and blood gas analysis showed marked hypoxemia. A differential cell count of bronchoalveolar lavage fluid showed a high level of lymphocytes; and examination of a specimen obtained by transbronchial lung biopsy revealed edema of the alveolar walls, lymphocyte infiltration, and marked proliferation of type II alveolar epithelial cells. Administration of etoposide was stopped and steroid therapy was given. The symptoms, hypoxemia, and bilateral reticulonodular shadows resolved. The clinical course along with the findings from examination of bronchoalveolar lavage fluid and of the biopsy specimen, suggest that this patient had drug pneumonitis caused by oral etoposide.

Administration, Oral↗

[Mycoplasma pneumoniae pneumonia with diffuse nodular shadows and right hilar lymphadenopathy].

A 51-year-old man was admitted to our hospital because of fever, a productive cough, and dyspnea. His chest X-ray film revealed diffuse reticulonodular shadows and right hilar lymphadenopathy. A chest CT scan revealed thickened bronchial walls and diffuse centriacinar or centrilobular nodular shadows. Serologic testing provided conclusive evidence of Mycoplasma pneumoniae infection. The diffuse pattern and hilar lymphadenopathy on chest X-ray films are uncommon in this disease, and they caused some uncertainty regarding the correct diagnosis. M. pneumoniae attaches to cells of the respiratory tract and produces a locally acting cytotoxin. Immunologic mechanisms have been shown to play an important role in the pathogenesis of pneumonia. This case suggests that immunologic mechanisms are an important factor in diffuse lung lesions.

Humans↗

[Five cases of pneumonitis induced by sho-saiko-to].

We report five cases of pneumonitis induced by sho-saiko-to. The patients complained of coughing (4/5), dyspnea (4/5), and pyrexia (3/5). The duration of sho-saiko-to treatment ranged from 4 to 1155 days. Abnormal laboratory findings included high levels of C-reactive protein (4/5), leucocytosis (4/5), severe hypoxemia (4/5), low vital capacity (3/5), and low diffusing capacity (5/5). Chest X-ray and CT films revealed diffuse reticulonodular or ground-glass shadows in both lung fields (4/5). Bronchoalveolar lavage was done in three cases, and revealed lymphocytosis in two cases and abnormally low CD4/8 ratios in three cases. The results of lymphocyte stimulation tests against sho-saiko-to and its component were positive in 3 of 5 cases. After discontinuation of sho-saiko-to, corticosteroids were given in all cases. Symptoms were relieved, and laboratory data and chest X-ray findings returned forward normal. Sho-saiko-to toxicity should be included in the differential diagnosis of pneumonitis. If drug-induced pneumonitis is suspected, administration of sho-saiko-to should be stopped and corticosteroid therapy should be given immediately.

Aged↗

[Non-Hodgkin's lymphoma associated with polymyositis].

A 67-year-old man was admitted to with severe nasal congestion. One year previously, he had been suffered from polymyositis (PM) and had been treated with prednisolone. Physical examination and computed tomography revealed a mass in the upper pharynx. Biopsy revealed non-Hodgkin's lymphoma (diffuse medium, B-cell type). Bone marrow aspiration also revealed the infiltration by lymphoma cells. The patient achieved a complete remission after combination chemotherapy (cyclophosphamide, adriamycin, vincristine, prednisolone). However, one month later, he suffered from central nervous system involvement of lymphoma cells, and he died of an aspiration pneumonia. Polymyositis/dermatomyositis associated with non-Hodgkin's lymphoma is extremely rare.

Aged↗

Mechanism for mouse strain differences in the protective effect of Sudan III against the in vivo genotoxicity of 7,12-dimethylbenz[a]anthracene.

The effect of Sudan III-pretreatment on the in vivo genotoxicity of 7,12-dimethylbenz[a]anthracene (DMBA) was investigated using C57BL/6 (B6) and DBA/2 (D2) mice. A significant increase in the frequency of micronucleated reticulocytes was observed in both strains of mice treated with DMBA. The increase was significantly reduced in B6 but not D2 mice by Sudan III-pretreatment. However, enhancement of metabolic activation was found in the Ames assay in the hepatic post-mitochondrial supernatant fraction (S9) from Sudan III-treated animals. It was greater with S9 from B6 than S9 from the D2 group. When the assay was performed in the presence of glutathione, this enhancement was significantly reduced. Sudan III induced some drug metabolizing enzymes, mainly CYP1A and glutathione S-transferase was also induced. The induction of CYP1A was more effective in B6 than D2 mice. These results support our hypothesis that the simultaneous induction of Phase I and II drug metabolizing enzymes is the mechanism for the chemoprevention by Sudan III and suggest that strong induction of CYP1A might be essential for a protective effect.

9,10-Dimethyl-1,2-benzanthracene↗