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Biomedical subjects

T Higashi

Publications and source records attributed to T Higashi.

At least 181 records · Page 10Linked to original sources

Cathepsin B in the growth of colorectal cancer: increased activity of cathepsin B in human colorectal cancer.

Cathepsin B, a thiol protease, is involved in cancer metastasis. To clarify the role of cathepsin B in tumor progression in human colorectal cancer, the relationship between its activity, immunohistochemical staining, and clinical tumor progression was investigated. Cathepsin B activity in adenocarcinomas was significantly elevated compared with that in the tumor-bearing tissue. Furthermore, the tumor/tumor-bearing tissue (T/Tb) ratio of the activity was significantly higher than that of colorectal adenoma. Immunohistochemical studies demonstrated intense staining in the cancerous tissue. With respect to the clinical stage of tumors, the activity tended to be higher in tumors that had invaded the serosa or subserosa than in those that invaded the proper muscle. The results suggest that cathepsin B participates in the progression of human colorectal cancer, and its increased expression is a sensitive marker of the differentiation between colorectal adenoma and adenocarcinoma.

Adenocarcinoma↗

Usefulness of indocyanine green injection during ultrasound-guided liver biopsy for the diagnosis of small hepatocellular carcinoma.

To diagnose hepatocellular carcinoma (HCC) functionally and immediately, we examined the usefulness of indocyanine green (ICG) injection during ultrasound-guided liver biopsy. Liver specimens were obtained after intravenous ICG injection by ultrasound-guided biopsy from 251 space-occupying lesions (SOL) in 136 patients. The tissues were immediately examined for ICG uptake using an infrared Vidicon camera and were also subjected to histopathological examinations. Of the 112 ICG-negative biopsy specimens, 105 were histologically diagnosed as HCC, 6 as dysplastic nodules (DN) and 1 as a regenerative nodule (RN). Of the 139 ICG-positive specimens, 18 were diagnosed as HCC, 1 as DN and 120 as RN. The sensitivity of the absence of ICG uptake (SEAIU), the specificity of the absence of ICG uptake (SPAIU), and the positive predictive value of the absence of ICG uptake (PPAIU) for the diagnosis of HCC were 85.3%, 94.5% and 93.8%, respectively. Of the 251 SOLs, 184 were less than 2 cm. SEAIU, SPAIU and PPAIU for the diagnosis of these small HCC were 85.3%, 94.5% and 91.4%, respectively. These results support the reliability of ICG injection during ultrasound-guided liver biopsy to diagnose even small HCC.

Aged↗

Advanced glycation end products and their recognition by macrophage and macrophage-derived cells.

Modification of proteins by long-term incubation with glucose leads to the formation of advanced glycation end products (AGEs). AGE proteins are taken up by macrophages via the AGE receptor, which is similar to the macrophage scavenger receptor (MSR). In the present study, we compared the ligand specificity of the AGE receptor with that of MSR by three different experiments. The endocytic uptake of 125I-acetyl-LDL by RAW cells was effectively inhibited by unlabeled AGE-bovine serum albumin (BSA), whereas the inhibitory effect of acetyl-LDL on 125I-AGE-BSA was partial. Polyanions showing an effective inhibition for endocytic uptake of AGE-BSA were not always inhibitory for endocytic degradation of acetyl-LDL. These data, together with those obtained by three-dimensional fluorescence-activated cell sorter analysis, indicate that AGE proteins are recognized by more than two receptors, of which MSR is at least one. Finally, we examined whether MSR could mediate the endocytic uptake of AGE proteins by Chinese hamster ovary cells overexpressing bovine type II MSR (CHO-SRII cells). 125I-AGE-BSA underwent endocytic degradation by CHO-SRII cells, and this was effectively inhibited by unlabeled acetyl-LDL. These results clearly show that MSR mediates the endocytic uptake of AGE proteins, suggesting a new role of MSR in biological recognition of AGE in vivo.

Animals↗

Aortic valve replacement for aortic regurgitation due to Kawasaki disease. Report of two cases.

Two cases of severe aortic regurgitation due to Kawasaki disease are reported. Both patients were diagnosed as having Kawasaki disease in their infancy, and were followed up by a pediatrician. Aortic regurgitation was detected 18 months in one case and 36 days in the other case after onset of the illness. With the passage of time, the aortic regurgitation increased and aortic valve replacement was scheduled in both patient at the age of 13. On admission, two-dimensional echocardiography showed thickening of the aortic cusps, and severe aortic regurgitation was detected by color flow Doppler studies. Successful aortic valve replacement was performed, and histological studies of the cusps showed sequelae of valvulitis. In conclusion, aortic regurgitation is a rare complication of Kawasaki disease, and the aortic valve function, especially occurrence of aortic regurgitation, should be carefully observed in patients with a past history of Kawasaki disease.

Adolescent↗

[Imaging of somatostatin receptor using 111In-pentetreotide].

Recently radiolabeled somatostatin analog, [111In]pentetreotide, was developed and its usefulness for the diagnosis and localization of neuroendocrine tumors has been described. In this paper, we reported the results of [111In]pentetreotide scintigraphy in four patients with gastroenteropancreatic endocrine tumors. Two patients with metastatic gastrinoma, one patient with gastric carcinoid, and one patient suspected with gastrinoma, were injected with 119-156 MBq of [111In]pentetreotide. Planar and SPECT images were obtained 4, 24, and 48 hours postinjection. Both primary and metastatic tumors were well visualized in patients with metastatic gastrinoma. Especially in one patient small liver metastases which were not detected by CT or MRI were imaged. We could not obtain positive images in the other two patients. Four-hour or 24-hr images were better than 48-hr images because of higher count density and lower gut activity. No significant adverse effect were seen in any patient. [111In]pentetreotide scintigraphy is a useful procedure for the localization of gastroenteropancreatic endocrine tumors.

Aged↗

[Surgical treatment for active infective endocarditis].

Between April 1975 and December 1995, 33 patients with active infective endocarditis underwent surgical treatment at our hospital. The location of diseased valve was shown as ; 18 in aortic, 11 in mitral, and 4 in aortic and mitral position. Of these, 14 patients had an annular abscess or mycotic aneurysm. All patients achieved antibiotic therapy previously, and predominant indication for operation was congestive heart failure. All patients underwent valve replacement. The reconstructive procedures for 14 patients with paravalvular involvement were as follows ; direct closure : 5 cases, direct closure+tilted prosthesis technique : 5 cases, and another 4 cases were, patch closure of VSP resulting from a septal abscess, patch closure+translocation, translocation, and reconstruction of annulas with pericardial patch. There were five (15.2%) operative and hospital deaths and actuarial survival rate was 81% and 61% at 5 and 10 years after operation. Including one who died early after operation, there were 5 cases with postoperative paravalvular leakage and its main cause were persistent infection. In conclusion, it considered that the principles of treating active infective endocarditis is to decide the optimal timing for operation, debride the infected tissue, and close the defect completely.

Adolescent↗

[Immunodeficiency with thymoma (Good's syndrome) similar to sino-bronchial syndrome].

A 58-year-old man was admitted to our hospital because of recurrent pulmonary infections that began three years previously. Laboratory data showed hypogammaglobulinemia and a chest computed tomogram showed diffuse bilateral micronodular shadows and an anterior mediastinal tumor. Immunodeficiency with thymoma (Good's syndrome) was diagnosed. After undergoing a thymectomy, he received intravenous gamma-globulin injections once a month for prophylaxis. Good's syndrome occurs rarely in Japan. A solid tumor-like shadow is not necessarily observed in routine chest X-ray studies, and hypogammaglobulinemia is one sign of this syndrome. The hypogammaglobulinemia of Good's syndrome should be carefully differentiated from that of other immunodeficiency diseases such as common variable immunodeficiency, the acquired immunodeficiency syndrome, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and multiple myeloma (non-secretory type).

Agammaglobulinemia↗

[Anesthesia for cesarean section: drug transfer to fetus during anesthesia].

One case of prenatally diagnosed congenital diaphragmatic hernia was reviewed in terms of the anesthetic managements. Concentrations of diazepam, pancuronium and fentanyl were measured in maternal, fetal and umbilical serum. As expectedly, the transition of diazepam through the placenta was large and the concentration of diazepam in the fetal serum was equal to that of maternal serum, but only a small amount of pancuronium was transferred.

Adult↗

Cellular distribution of 92-kd type IV collagenase/gelatinase B in human hepatocellular carcinoma.

To examine the possible involvement of gelatinase B in human hepatocellular carcinoma (HCC), cellular localization of transcripts and protein of gelatinase B were studied by using in situ hybridization and immunohistochemistry. Transcripts for gelatinase B were observed in tumor cells in 22 cases of 27 HCCs and also in dysplastic nodules. However, there was no significant difference in the expression among histological grades of HCC. The expression was mostly homogeneous, but the intensity varied with the nodules. Of 13 cases with capsular invasion, 12 expressed gelatinase B, whereas 10 of 14 without capsular invasion did (P < 0.05). Gelatinase B transcripts were commonly observed in the sinusoidal cells of the hepatic lobules, in mesenchymal cells both in fibrous capsules and around the necrosis, and also in some undefined cells of the portal tracts of noncancerous liver. Localization of gelatinase B protein was mostly similar to but sometimes different from that of the transcripts in cancer nodules. In conclusion, the expression of gelatinase B appears to be an important characteristic of malignant transformation of hepatocytes. The findings suggest that gelatinase B synthesized by cancer cells plays an important role in the growth and invasion of HCC by degrading surrounding extracellular matrices.

Adult↗

[A case of recurrent squamous cell carcinoma of cervix successfully treated with BOMP].

Combination chemotherapy consisting of bleomycin, vincristine, mitomycin C and cisplatin (BOMP) was applied to a case (57 years old) with recurrence of squamous cell carcinoma of the cervix. The patient with FIGO stage IIIb cervical carcinoma had been treated with radiotherapy seven years ago. She was affected by malignant pericardial effusion, and was treated with direct intrapericardial administration of cisplatin (20 mg). After instillation, ultrasonography and computed tomography showed the wall thickening of colon and marked ascites. Barium enema showed the circumferential narrowing and serrations of colon, and it was diagnosed to be carcinomatous peritonitis. She was treated with BOMP consisting of BLM (5 mg, i.m., days 1 - 5), VCR (1 mg, i.v., day 5'), MMC (8 mg, i.v., day 5), and CDDP (70 mg, d.i.v., day 5). After three courses of BOMP therapy, she achieved a complete response with few toxic effects and did not require special care. She has been free of disease for six months and her performance status is 0. This encouraging result warrants the use of this combination chemotherapy regimen in other patients with recurrent squamous cell carcinoma of the cervix.

Antineoplastic Combined Chemotherapy Protocols↗

Activation of heat shock factor 1 in rat brain during cerebral ischemia or after heat shock.

Recently, many studies have demonstrated the induction of stress proteins in the mammalian nervous system under various pathological conditions. These altered genetic programs may function to protect individual cells against stressful conditions. However, little is known about the molecular mechanisms regulating these stress responses in animals. We report here the activation of a heat shock factor (HSF) in the rat brain during cerebral ischemia or after heat shock. Gel mobility shift assays revealed an increase in DNA binding activity to the heat shock element (HSE) during the early phases of ischemia. Supershift experiments using specific antisera against HSF1 and HSF2 showed that the ischemia-induced HSE-binding activity was mainly due to HSF1. In the heat-shocked brain, HSF1 was also activated, and the HSE-binding activity was higher in the cerebellum than in the cerebral cortex or hippocampus; Western blot analysis also showed that HSF1 was more abundant in the cerebellum than in the other two brain regions. Our results indicate that heat shock gene transcription is regulated by the activation of HSF1 in both cerebral ischemia and heat shock, and that different brain regions display differential sensitivities in their stress response. The cellular signals for heat shock gene transcription under in vivo pathological conditions will also be discussed.

Animals↗

Advanced glycation end products stimulate plasminogen activator activity via GM-CSF in RAW 264.7 cells.

The effects of advanced glycation end products (AGE) on the plasminogen activator (PA) activity were investigated with murine macrophage cell line RAW 264.7 cells. AGE-bovine serum albumin (BSA) showed a dose-dependent induction for the urokinase-type PA (uPA) activity. The uPA induction by AGE-BSA was effectively suppressed by the antibody against granulocyte-macrophage colony-stimulating factor (GM-CSF). The uPA activity of these cells was also induced by ligands for the macrophage scavenger receptor (MSR). These data provide evidence that AGE-BSA stimulates the uPA activity via GM-CSF through MSR in RAW cells. These findings, taken together with a recent demonstration of endocytic uptake of AGE-proteins by MSR in vitro and the presence of AGE-proteins in atherosclerotic lesions, strongly suggest that the uPA induction by AGE-proteins via MSR plays an important role in human atherogenesis.

Animals↗

Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end products of the Maillard reaction.

Modification of proteins by long-term incubation with glucose leads to the formation of advanced glycation end products (AGE). Recent immunological demonstration of the presence of AGE proteins in several human tissues suggests that they may be involved in aging, diabetic complications and atherosclerosis. AGE proteins are taken up by macrophages via the AGE receptor, which is similar to the macrophage scavenger receptor (MSR). In the present study, we examined whether MSR could mediate the endocytic uptake of AGE proteins by using Chinese hamster ovary (CHO) cells overexpressing bovine type II MSR (CHO-SRII). 125I-labelled AGE bovine serum albumin (125I-AGE-BSA) as well as 125I-acetylated low-density lipoprotein (125I-acetyl-LDL) underwent endocytic degradation by CHO-SRII cells, but not by control CHO cells. Endocytic degradation of 125I-acetyl-LDL and 125I-AGE-BSA by CHO-SRII cells was significantly inhibited by unlabeled AGE-BSA, as well as by acetyl-LDL. Immunoelectron microscopic studies using both AGE-BSA conjugated with gold particles and anti-(bovine MSR) antibody (D2) revealed co-localization of gold particles and the reactive sites for the antibody at coated pits of plasma membranes as well as in endosomes. These results clearly show that MSR mediates the endocytic uptake and degradation of AGE proteins, suggesting a new role of MSR in biological recognition of AGE in vivo.

Animals↗

Beta-migrating very low density lipoproteins induce foam cell formation in mouse mesangial cells.

To elucidate whether beta-migrating very low density lipoproteins (beta-VLDL) induce foam cell formation in mesangial cells or not, surface binding and foam cell formation with beta-VLDL were studied in mouse mesangial cells. Specific binding kinetics for beta-VLDL and low density lipoproteins (LDL) on the mesangial cells were observed with Kd = 3.8 and 13.7 micrograms/ml, and Bmax = 65.9 and 71.9 ng/ml cell protein at 4 degrees C, respectively. The binding of beta-VLDL was inhibited by excess amounts of LDL or beta-VLDL, but not by acetyl-low density lipoproteins. Ligand blotting using beta-VLDL or LDL and immunoblotting using anti-human LDL receptor monoclonal antibody detected the same apparent single protein (approx. 130 kDa). Incorporation of [14C]oleate into cholesteryl ester in mouse mesangial cells was enhanced by beta-VLDL to 3-fold higher than that by LDL, and it was inhibited by chloroquine or anti-human LDL receptor monoclonal antibody. The light microscopic findings also demonstrated that cholesteryl ester deposition increased in these cells incubated with beta-VLDL, but not with LDL. In conclusion, beta-VLDL was specifically taken up by receptor-mediated endocytosis in mouse mesangial cells through LDL receptors, resulting in foam cell formation.

Animals↗

Localization of advanced glycation end products of Maillard reaction in bovine tissues and their endocytosis by macrophage scavenger receptors.

In aged bovines, the accumulation of advanced glycation end-products (AGEs) in macrophages, endothelial cells, adventitial cells, or pericytes; epithelial or parenchymal cells of some organs such as the liver, adrenals, and kidneys; neuronal cells in the brain; and extracellular matrix was demonstrated by immunohistochemistry using anti-AGE monoclonal antibody 6D12. Immunoelectron microscopy demonstrated the localization of AGEs in the endosomal and lysosomal compartments of various types of cell and in the extracellular matrix. By biochemical characterization of the interaction of AGEs with bovine alveolar macrophages using [125I]AGE-bovine serum albumin (BSA), the cell association and subsequent endocytic degradation of [125I]AGE-BSA were confirmed. To investigate the possible participation of scavenger receptors in the endocytosis of AGEs, these cells were incubated with AGE-BSA conjugated with colloidal gold particles (AGE-BSA-Au particles) and examined by immunoelectron microscopy with a monoclonal antibody for bovine macrophage scavenger receptors, D2. In these macrophages, AGE-BSA-Au particles were bound to the D2-positive scavenger receptors on the surface membrane, endocytosed, and directed to secondary lysosomes. The scavenger receptors were dissociated from the ligands in late endosomes and recycled via a trans-Golgi system to the cell surface membrane. These data suggest that scavenger receptors participate in the endocytic process of AGEs by macrophages.

Aging↗

Acetone excretion into urine of workers exposed to acetone in acetate fiber plants.

To develop a proper protocol for biological exposure monitoring of acetone, we evaluated whether exposure to acetone on the previous day affects the biological monitoring value at the end of a work day. One hundred and ten male workers exposed to acetone in three acetate fiber manufacturing plants were monitored using a liquid passive sampler on two consecutive working days after 2 days without exposure. Urine samples were collected at the start of the workshift and the end of the shift on both days for each subject. For ten exposed workers urine samples were collected approximately every 2 h during and after the first working day until the following morning. Acetone concentrations in urine (Cu) at the start of the first working day were 1.3 +/- 2.4 (range: ND-14.1) mg/l in nonexposed workers and 2.4 +/- 5.6 (range: ND-40.3) mg/l in exposed workers. The urinary acetone concentration at the beginning of the second working day indicated that urinary levels of acetone do not decline to background level by the following morning when exposure concentration exceeds 300 ppm. However, linear regression analysis demonstrated that the relationship between environmental exposure level and urine level was similar on the 1st day and the 2nd day. Thus, although urine acetone levels did not return completely to baseline after high exposures, under the present exposure levels the exposure on the previous day did not significantly affect urinary acetone at the end of the workshift of the next day.

Acetone↗

Effects of nickel oxide on the production of tumor necrosis factor by alveolar macrophages of rats.

To evaluate the effect of green nickel oxide (NiO) on the production of tumor necrosis factor (TNF) by alveolar macrophages, alveolar macrophages were exposed to NiO in vitro and in vivo. For the in vitro study, rats alveolar macrophages were incubated with NiO on a microplate for 24 h. TNF activity in the culture supernatant was determined by the L929 bioassay. Rats alveolar macrophages cultured with 100 and 200 micrograms/mL of NiO in vitro induced the production of TNF, however, it was not statistically significant compared with the control that was free from NiO exposure. For exposure in vivo, rats were divided into two groups. Five were exposed to a daily concentration of 11.7 +/- 2.0 mg/m3 of NiO for an 8-hr/d, 5 d/wk, for 4 wk, and five rats (control) were kept in a cage and not exposed to NiO. Bronchoalveolar lavage was performed and the recovered alveolar macrophages were incubated on a microplate for 24 h. TNF production by exposed alveolar macrophages was significantly higher than that of controls.

Acid Phosphatase↗

Multiple channels for occupational health services to small-scale enterprises in Japan.

This study was performed to clarify the characteristics of multiple channels for occupational health services (OHS) to small-scale enterprises (SSEs) in Japan employing less than 50 workers by reviewing relevant research papers. OHS were provided to SSEs by both government organizations and non-government organizations. Government organizations included the Japanese Industrial Safety & Health Association, regional occupational health centres, prefectural occupational health promotion centres, and other health centres. Non-government organizations were parent companies, occupational health organizations, hospitals, medical associations, trade associations and health insurance societies. The quality of OHS in terms of provision of health personnel and the nature of their services differed greatly between the organizations. Health care programmes were more popular than management of the work environment or working practices in OHS to SSEs. Few organizations provided comprehensive OHS to SSEs. At present, parent companies and occupational health organizations appear to provide the best OHS available to SSEs in Japan.

Commerce↗