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Biomedical subjects

T Honma

Publications and source records attributed to T Honma.

At least 91 records · Page 5Linked to original sources

The mannose-binding protein A region of glutamic acid185-alanine221 can functionally replace the surfactant protein A region of glutamic acid195-phenylalanine228 without loss of interaction with lipids and alveolar type II cells.

Pulmonary surfactant protein A (SP-A) is a C-type lectin that regulates the uptake and secretion of surfactant lipids by alveolar type II cells and binds dipalmitoylphosphatidylcholine (DPPC) and galactosylceramide (GalCer). We isolated mannose-binding protein A (MBP-A) from rat sera, which is structurally analogous to SP-A, and examined if it was functionally equivalent to SP-A. We found that MBP-A did not possess the ability to interact with lipids and type II cells. The purpose of this study was to investigate the SP-A region involved in binding lipids and interacting with type II cells by using chimeric proteins with MBP-A. Chimeras AM1, AM2, and AM3 were constructed with SP-A/MBP splice junctions at Cys218/Gln210, Lys203/Cys195, and Gly194/Glu185, respectively. All of the chimeras bound DPPC and GalCer with activity comparable to recombinant SP-A. The three chimeras retained the ability to induce phospholipid vesicle aggregation and augment lipid uptake by type II cells, albeit to a lesser extent than wild type SP-A. The chimeras inhibited lipid secretion from type II cells with an IC50 of 0.5 microg/mL and competed effectively for SP-A receptor binding. In addition all these chimeras contained the epitope for monoclonal antibody 1D6, which blocks specific SP-A function. From these results, we conclude that the MBP-A region of Glu185-Ala221 can functionally replace the homologous SP-A region of Glu195-Phe228 without loss of interaction with lipids and type II cells.

Acute-Phase Proteins↗

Changes in plasma lipoproteins as toxicity markers for carbon tetrachloride, chloroform, and dichloromethane.

Effects of single intraperitoneal (i.p.) administration of carbon tetrachloride (CCl4), chloroform (CHCl3), and dichloromethane (CH2Cl2) on lipoproteins in plasma and liver were investigated in rats. Changes in lipoproteins caused by these solvents were compared with changes in traditional hepatotoxicity markers such as GPT (ALT). Following the administration, concentrations of lipoproteins (VLDL, LDL, HDL), triglyceride, cholesterol, and GPT activity in plasma were determined through changes in liver weight, liver content of triglyceride, malon dialdehyde (MDA), and glutathione (GSH). Time-course study revealed that changes in plasma and liver reached their peaks at 19 or 32 hr following the administration of CCl4 or CHCl3. Peaks of changes were observed at 8 or 19 hr following the administration of CH2Cl2. Dose dependency of these changes was investigated at dosages of 3, 30, and 300 mg/kg of CCl4 or CHCl3, and 300, and 1,000 mg/kg of CH2Cl2. Significant decreases in triglyceride and apolipoproteins in VLDL fraction were observed at 3 mg/kg of CCl4. Such VLDL components decreased at 30 mg/kg of CHCl3. HDL decreased significantly at 300 mg/kg of CH2Cl2 and marked increase in LDL occurred at 1,000 mg/kg of the solvent. Liver weight and liver content of triglyceride and MDA significantly increased at 30 mg/kg of CCl4, while significant increase in GPT activity was observed at 300 mg/kg of CCl4 and CHCl3. GPT increased significantly at 1,000 mg/kg of CH2Cl2. These results revealed that changes in plasma lipoproteins can serve as sensitive and simple markers for liver disorders caused by chlorinated hydrocarbon solvents such as CCl4, CHCl3, or CH2Cl2.

Analysis of Variance↗

[Usefulness of helical DIC-CT in pancreaticobiliary maljunction].

[PURPOSE]: To determine the usefulness of helical CT during drip infusion cholangiography (DIC-CT in patients with pancreaticobiliary maljunction. [MATERIALS AND METHODS]: DIC-CT was performed in six patients with pancreaticobiliary maljunction. After drip infusion of 100 ml of Iotroxic acid meglumine, helical CT was performed. One mm or 1.5 mm interval images were reformatted from the raw data. Thereafter, multi-plannar reconstruction (MPR) images were obtained from the reformatted images. The reformatted images and the MPR images were reviewed. [RESULTS]: In all cases, the form of the union was visualized. In two patients, a contrast defect was shown in the common bile duct arising from the union of the pancreatic duct. The defects were considered due to pancreatic juice reflux into the common bile duct. In the other two patients, the contrast medium in the common bile ducts was regurgitated into the pancreatic duct. [CONCLUSION]: DIC-CT was very useful in the evaluation of pancreaticobiliary maljunction, because of its functional characteristics, high resolution and three-dimensional data.

Acute Disease↗

[Non-surgical therapy for ulcerative colitis].

Ulcerative colitis involving primarily the mucosa of the colon and rectum is a diffuse and nonspecific inflammatory disease. Immunocompetent cells infiltrating in the inflammed mucosa are mainly lymphocytes, macrophages and neutrophils. These activated cells produce proinflammatory cytokines such as IL-1, IL-6, IL-8 and TNF alpha and inflammatory activators such as PAF, leukotriene, prostaglandins, free radicals and proteases, resulting in acute on chronic states. Non-surgical therapy for ulcerative colitis includes basic medical therapy with sulfasulphapyridine, 5-ASA, corticosteroids and immune suppressive drugs as well as new therapies, which are leukocytapheresis, granulocytapheresis, anticytokine therapy with antiTNF alpha monoclonal antibody, IL-1ra and IL-10, intravenous treatment of massive immunoglobulins and transdermal nicotine therapy.

Colitis, Ulcerative↗

[A case of juvenile Huntington's disease presenting dystonia and confirmed by DNA analysis].

We reported a 13-year-old boy with juvenile Huntington disease diagnosed by DNA analysis. Symptoms started with dysarthria at 6 years of age, which was followed by progressive dysgraphia and gait disturbance due to dystonia from 7 years, and by epileptic seizures from 12 years. Magnetic resonance imaging revealed atrophy of the bilateral caudate nuclei and T2- and proton-weighted high intensity area in both putamina. The CAG (cytosine-adenine-guanine) trinucleotide repeat on chromosome 4 p16 was markedly expanded to 81. For a child with dystonia with mental deterioration, juvenile Huntington disease should be considered in the differential diagnosis.

Adolescent↗

[Transarterial embolization of a vein of Galen aneurysm: a case report].

This report describes a case of a vein of Galen aneurysm. A 6-month-old baby with a slight head injury was referred to our hospital. CT scans and MR images demonstrated a vein of Galen aneurysm. Left carotid angiogram showed a vein of Galen aneurysm with a large feeding artery from the posterior cerebral artery. Transarterial embolization was performed using Galen coils and Interlocking Detachable Coils. Angiograms after the second embolization revealed complete occlusion of the aneurysm and postoperative course was uneventful.

Cerebral Angiography↗

[Histological findings in aneurysm treated with IDC: scanning electron microscopical study].

We reported the scanning electron microscopic findings of an aneurysm embolized with interlocking detachable coils (IDC). A 78-year-old man was referred to our hospital because of left hemiparesis and dysphagia. CT scan showed multiple lacunar infarction in the bilateral corona radiata. Angiography demonstrated a small incidental aneurysm of the right internal carotid artery (IC-PC junction). The left hemiparesis gradually improved and 2 weeks after admission the aneurysm was treated with IDC. Three coils were placed in the aneurysm and post-operative angiography demonstrated complete embolization. Dysphagia caused by the pseudobulbar pulse did not improve and, 4 weeks after endovascular surgery, the patient died of aspiration pneumonia. An autopsy was performed and the scanning electron microscopical findings of the aneurysm showed development of endothelial cells on the coil surface. Many clinical reports supported the usefulness of Guglielmi detachable coils (GDC) and several experimental reports demonstrated the intimal proliferation in aneurysms embolized with coils. However, pathological changes of the aneurysms treated with coils have been reported in only four clinical cases. There was no evidence of endothelialization in any of these cases. To our knowledge, our case is the first report describing the endothelial proliferation over the coils. It is necessary to accumulate histopathological data and long-term follow-up in humans treated with coils.

Aged↗

[Dissecting aneurysm of the middle cerebral artery with subarachnoid hemorrhage and brain infarction: a case report].

This report describes a surgical case of a dissecting aneurysm of the left middle cerebral artery with subarachnoid hemorrhage and ischemic insult. A 48-year-old man with pure motor aphasia was referred to our hospital. CT scans demonstrated subarachnoid hemorrhage in the left frontal region. CT scans on the next day showed a small brain infarction in the left precentral artery and central artery territories. The first left carotid angiograms showed stenosis at the M2 portion of the middle cerebral artery. On the 16th day, the second left carotid angiograms revealed a pearl and string sign. We diagnosed a dissecting aneurysm of the middle cerebral artery. The dissecting aneurysm was wrapped using the pterional approach and STA-MCA anastomosis was also performed. The postoperative course was uneventful and the motor aphasia improved.

Aortic Dissection↗

[Congenital atresia and stenosis of the intestine].

During the period between 1946 and 1996, 59 patients of intrinsic duodenal obstruction and 67 of intrinsic jejunoileal obstruction were treated in our institute. Analysis of data obtained from the patients revealed that the duodenal obstruction was the most successfully treated by diamond-shaped duodenoduodenostomy, jejunal obstruction by resection of the dilated oral blind end, tapering jejunoplasty and ileal obstruction by resection of the dilated blind end and anastomosis or ileostomy in case with peritonitis. Associated anomalies in duodenal obstruction, anastomotic malfunction and postoperative short bowel syndrome in jejunal obstruction and complicated peritonitis in ileal obstruction were the most effective as prognostic factors.

Duodenal Obstruction↗

Interaction of phospholipid liposomes with plasma membrane isolated from alveolar type II cells: effect of pulmonary surfactant protein A.

Pulmonary surfactant protein A (SP-A) augments the uptake of phospholipid liposomes containing dipalmitoylphosphatidylcholine (DPPC) by alveolar type II cells. The SP-A-mediated uptake process of lipids by type II cells have not been well understood. In the present study we investigated the SP-A-mediated interaction of phospholipids with plasma membrane isolated from alveolar type II cells. SP-A increased the amount of liposomes containing radiolabeled DPPC associated with type II cell plasma membrane by 4-fold compared to the control without SP-A when analyzed by sucrose density gradient centrifugation. This effect is dependent upon the SP-A concentration. The enhancement was inhibited by anti-SP-A antibody and EGTA. When type II cell plasma membrane and liposomes containing [14C]DPPC and [3H]triolein were coincubated with or without SP-A, analysis on sucrose density gradients revealed that the profiles of [14C]DPPC and [3H]triolein in each fraction were almost identical with or without SP-A, indicating that SP-A mediates the binding of liposomes to plasma membrane but not transfer of DPPC. SP-A increased the association of liposomes containing DPPC with the membrane by 2-fold more than that containing 1-palmitoyl-2-linoleoyl-phosphatidylcholine (PLPC). SP-A induced aggregation of phospholipid liposomes containing PLPC as well as those containing DPPC, but the final turbidity of DPPC liposomes aggregated by SP-A was only by 15% greater than that of PLPC liposomes. The amount of DPPC liposomes associated with the plasma membrane derived from type II cells was 2-fold greater than that from liver. We speculate that the SP-A-mediated interaction of lipids with type II cell plasma membrane may contribute, in part, to the lipid uptake process by type II cells.

1,2-Dipalmitoylphosphatidylcholine↗

Effect of exposure to four organic solvents on hepatic cytochrome P450 isozymes in rat.

Changes of cytochrome P450 isozymes in livers of rats after exposure to four solvents at 4000 ppm for 6 h, were studied by enzyme assays and immunochemical detection using antibodies to cytochrome P450 isozymes. Toluene, benzene and trichloroethylene (TRI) exposure resulted in a significant increase in the activities of nitrosodimethylamine demethylase (152%, 134% and 118%) and 7-pentoxyresorufin O-depentylase (14-, 5- and 2.5-fold), respectively. 1,1,1-Trichloroethane (TCE) showed little effect on the activities of the enzymes. Anti-CYP2E1 and anti-CYP2B1/2 inhibitable activity of toluene side-chain oxidase was significantly enhanced in toluene-, benzene- and TRI-treated rats. Anti-CYP2C11 inhibitable activity was greatly reduced as compared with control. The change in CYP2E1 and CYP2C11 was confirmed by the increase and decrease in the activities inhibited by 4-methylpyrazole and cimetidine, respectively. Western blot analysis revealed that the increase in peak area of bands recognized by anti-CYP2E1 was consistent with toluene inhibition results. CYP2B1/2 was not detectable in control rats, but it was strongly induced by toluene, followed by benzene and TRI. Some increases in the peak areas of bands recognized by anti-CYP2A1 and CYP-4A1 were also observed in the three solvents exposed rat microsomes. Little immunoreactivity was found with anti-CYP1A1 in all microsomes, and no obvious change in peak area of bands recognized by anti-CYP3A and anti-CYP2C13 was observed. TCE exposure showed little effect on these bands. The formation of phenol and hydroquinone from benzene was enhanced to different degree by toluene, benzene and TRI. The hydroxylation of testosterone at 6 beta and 7 alpha was increased by benzene, and benzene and TRI, respectively. However, the metabolism at 16 alpha and 2 alpha was profoundly suppressed by the solvents except TCE. These results showed that the four solvents have different effects on specific cytochrome P450 isozymes and on the metabolism of both endogenous and exogenous substances.

Animals↗

Ultrastructure of multinucleated giant cell apoptosis in foreign-body granuloma.

To elucidate the role of apoptosis in the disappearance of multinucleated giant cells from the granulation tissue in cases of foreign-body granuloma, we induced a foreign-body reaction by implanting a collagen sponge into the dorsum of the rat and observed apoptotic changes within the multinucleated giant cells using electron microscopy. Two types of multinucleated giant cells were identified presenting apoptotic characteristics morphologically. One was characterized by apoptosis of only one nucleus, followed by cytoplasmic changes, rupture of the plasma membrane and necrosis evoking an inflammatory reaction. The other showed typical apoptotic changes in the majority or in all of the nuclei, followed by phagocytosis of the apoptotic syncytia. The results of the present study suggest that apoptosis occurring within only one nucleus might be triggered by overexpression of the p53 protein, because DNA abnormalities are confined to this single nucleus. In contrast apoptosis occurring simultaneously in the majority or all of the nuclei is most probably due to cell death caused by senescence.

Animals↗

Effect of K-ras mutation on morphogenesis of colorectal adenomas and early cancers: relationship to distribution of proliferating cells.

The authors evaluated the association of the K-ras mutation with the distribution of proliferating cells and the macroscopic appearance of colorectal tumors. A total of 122 colorectal adenomas and 96 early cancers were classified macroscopically as follows: (1) polypoid, exceeding 3 mm in height; (2) flat or hemispherically elevated 3 mm or less; and (3) depressed. The intramucosal areas of these tumors were examined by Ki-67 immunostaining and nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to detect proliferating cells and the K-ras codon 12 mutation. The distribution pattern of the Ki-67-positive cells was of two types: diffuse (D), being positive throughout the crypts, and superficial (S), being positive mainly in the superficial areas of the crypts. The K-ras mutation and the D type distribution of the Ki-67-positive cells were significantly less common (P < .005) in the nonpolypoid, depressed, or elevated tumors versus the polypoid tumors. The incidence of the K-ras mutation was significantly (P < .0001) associated with the D type distribution. The K-ras mutation may involve a disorder of cell proliferation that leads to the polypoid growth of colorectal tumors.

Adenocarcinoma↗

[Characteristics of hyperthermia-induced apoptotic cell death].

Hyperthermia shows considerable promise as a treatment modality for cancer. It is widely accepted that hyperthermia at doses that fall within the therapeutic range triggers cell death by apoptosis in susceptible cell populations, higher heat loads producing necrosis. The hyperthermia-induced apoptosis is characterized both by its distinctive ultrastructural features and by the occurrence of internucleosomal DNA cleavage. The thermosensitivity to apoptotic induction varies enormously from cell type to cell type. The molecular mechanism which makes a cell sensitive to induction of apoptosis by hyperthermia is not at present clear, however, understanding why some cell types are sensitive or resistant to apoptotic induction is important to achieve the immediate cell killing effect of hyperthermia on each individual cell type.

Animals↗