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Biomedical subjects

I Fukuda

Publications and source records attributed to I Fukuda.

At least 91 records · Page 5Linked to original sources

Characterization of new monoclonal antibodies to human insulin-like growth factor-II and their application in western immunoblot analysis.

Four immunoglobulin G1 class monoclonal antibodies (mAbs; 1D5, 1D9, 2B11, and 2H11) were produced against recombinant human insulin-like growth factor-II (rhIGF-II). Enzyme-linked immunosorbent assay established that these four mAbs specifically recognized rhIGF-II and hIGF-II, but not rhIGF-I. mAbs 1D5, 1D9, and 2H11 did not cross-react with mouse rIGF-II, although there are only six amino acid differences between mouse IGF-II and human IGF-II. The epitope for each mAb was partially defined by enzyme-linked immunosorbent assay using mouse-human chimera IGF-II mutants and other IGF-II mutants that were prepared by site-directed mutagenic procedures. These results indicated that the epitopes of mAbs 1D5, 1D9, and 2H11 are in the C-domain of hIGF-II around Ala32 to Ser36, and that of 2B11 is in the carboxyl-terminal end of the B- and A-domains of hIGF-II. A specific and sensitive RIA was developed using mAb 2H11. In this RIA, IGF-II variant ([RLPG/S29]IGF-II) and rhIGF-II competed equally with [125I]IGF-II for binding to mAb 2H11. Similar results were produced when mAbs 1D5, 1D9, and 2B11 substituted for 2H11. The potential usefulness of mAb 2H11 in an immunoblot procedure to characterize the heterogeneity of IGF-II in the sera and tumor tissues of patients with nonislet cell tumor hypoglycemia was evaluated. A procedure that combined acid-ethanol extraction of serum or tumor tissues and immunoaffinity concentration of the extracted IGF-II with mAb 2H11-immobilized resin was found to be an effective way to prepare the samples. In Western immunoblots, a quantity of rhIGF-II as low as 3 ng could be identified, whereas 200 ng rhIGF-I or rat IGF-II were not recognized. The levels of IGF-II in the sera of 12 patients with nonislet cell tumor hypoglycemia varied from normal to about twice normal. The mol wt (M(r)) of this IGF-II was between 10-17K. There was little of the processed 7.5K M(r) IGF-II in the sera of these patients. Finally, the source of the high M(r) forms of IGF-II was the tumor, because the ratios of high M(r) forms of IGF-II to 7.5K IGF-II changed dramatically from 99:1 and 91:9 to 4:96 and 32:68 in two patients after successful excision of their tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Characterization of insulin-like growth factor II (IGF-II) and IGF binding proteins in patients with non-islet-cell tumor hypoglycemia.

Insulin-like growth factor II (IGF-II) in serum and tumor extracts from five patients with non-islet-cell tumor hypoglycemia (NICTH) has been characterized. These tumors contained large quantities of IGF-II (2.4-14.2 micrograms/g tissues). The serum IGF-II levels in four of five patients were a little high and the serum IGF-I levels in five patients were low. The serum IGF-II/IGF-I ratios in these patients ranged from 24.1 to 64.2, and the values were significantly greater than those in normal subjects (1.7-7.1). When the sera were gel-filtered on a Sephacryl S-200 column under neutral conditions, the proportion of the free form of IGF-II was not increased. However, in four of five patients, an abnormal IGF-II-IGF binding protein complex was found. When serum IGF binding proteins (IGFBPs) were analyzed by Western ligand blotting, serum IGFBP-2 increased in these patients. When the tumor extracts and sera were gel-filtered on a Biogel P-60 column under acidic conditions, the majority of IGF-II in these sera was a big form of IGF-II. As compared to authentic IGF-II, insulin receptor reactivities and IGF-II receptor reactivities of tumor extracted IGF-II increased in two of three patients. These data indicate that in patients with NICTH, heterogenous IGF-II is produced in respect of size and bioactivities, and that the characteristics of IGF binding protein are altered. Thus, to find IGF-II producing tumors among extrapancreatic tumors associated with hypoglycemia, the quality of IGF-II as well as the quantity should be studied.

Aged↗

[Some problems of TS measurement after administration of fluoropyrimidines in colorectal cancer. Kinki Cooperative Study Group of Chemotherapy for Colorectal Carcinoma].

A joint multicenter comparative study of carmofur (HCFU) alone or HCFU+dipyridamole (DP) concurrent administration was conducted by the Kinki Colorectal Cancer Chemotherapy Society. In this study, the drugs were administered five days prior to surgery, and thymidylate synthetase (TS) inhibition rate at the primary lesion of colorectal cancer was determined. In addition, the effect of time after resection of the primary lesion before specimen cooling on the TS inhibition rate was investigated. The subjects were 87 registered patients who received colorectal cancer surgery during 4 months from October 1991 to January 1992. The time before postsurgical cooling was divided into four group; within 10 min (n = 67), 11-20 min (n = 8), 21-30 min (n = 7), and 31 min or longer (n = 5). The TS inhibition rates (mean +/- SD) were 0.45 +/- 0.22, 0.38 +/- 0.19, 0.30 +/- 0.21, and 0.04 +/- 0.05 respectively. The longer the time after resection of the primary lesion before specimen cooling, the more TS inhibition rate decreased. When the time before specimen cooling exceeds 30 min, the major part of TS combined with FdUMP exists in a free state. Therefore, it was considered not suitable as the material for the measurement.

Adult↗

Hemorrhage from spontaneous rupture of a parathyroid adenoma (a case report).

A case of extracapsular hemorrhage from spontaneous rupture of a parathyroid adenoma is reported. In the case presented here, adenoma was revealed by a sudden onset of a huge ecchymosis and hematoma of the entire anterior neck and right chest, causing recurrent nerve paresis. These cases of hemorrhage from rupture of silent parathyroid adenoma mimicking a dissecting thoracic aortic aneurysm are discussed.

Adenoma↗

Delayed washout of intratumor blood flow is associated with good response to intraarterial chemoembolization for liver metastasis of colorectal cancer.

BACKGROUND: We studied stagnation of the blood in hepatic metastatic lesions of colorectal cancer. METHODS: Twenty-two hepatic tumors in 11 patients with liver metastases of colorectal cancers were investigated in this study. With a catheter inserted into the roots of the proper hepatic artery, 5 to 10 mCi 133Xe was injected. The half-time (t1/2) was calculated for the tumor region based on the washout curve by the compartmental method and expressed as the intratumor retention time of the blood. RESULTS: Transcatheter arterial chemoembolization with iodized oil (Lipiodol) and cisplatin was effective in eight (50%) of 16 tumors that were hypervascular but in only one (17%) of six tumors that were hypovascular (p < 0.05). Regardless of the hypervascular tumor, transcatheter arterial chemoembolization was not effective in tumors that had shown a t1/2 of less than 80 seconds. Seven of eight good-responding lesions that were hypervascular and had a long t1/2 (187 +/- 74.6 seconds) revealed characteristic fireworks-shaped accumulation of Lipiodol. CONCLUSIONS: Transarterial infusion chemotherapy for liver metastasis of colorectal cancer was considered effective for hypervascular hepatic tumors with a long t1/2.

Aged↗

[Combination therapy of high dose doxifluridine (5'-DFUR)+mitomycin C (MMC) for advanced or recurrent colorectal cancer. Joint Research Group in the Osaka Area for Combination Therapy of 5'-DFUR with Other Drugs].

A co-study was conducted on treatment with high dose 5'DFUR+MMC in order to determine its effectiveness as a systemic chemotherapy in patients with advanced and recurrent colorectal cancers. The treatment schedule included 5'-DFUR given orally at a dose of 1,600 mg/body/day for five consecutive days, a two-day discontinuation, then repeated medication with the above, and MMC injected intravenously at a dose of 6 mg/m2 once every four weeks. One course consisted of four weeks, and courses were repeated as long as tolerated by the patients. Twenty-nine patients were registered for the study and 28 cases were perfectly capable of anti-tumor responses. The response rate was 25.5%, including: CR, 2; PR, 5; NC, 11; and PD, 10 cases. Responding cases were found in metastases to the lung, cervical lymph node and abdominal wall. Response rate was especially high in pulmonary metastases at 41.7% (5/12 cases). The slight side effects were mostly gastrointestinal in nature and did not necessitate drug discontinuance. The results suggest that treatment with high dose 5'-DFUR+MMC is useful for advanced and recurrent colorectal cancers, especially those with pulmonary metastases.

Administration, Oral↗

[Pseudo-false aneurysm of the left ventricle perforated into the right ventricle--a case report].

A case of pseudo-false aneurysm of the left ventricle perforated into the right ventricle was reported. The patient was 60-year-old male with acute inferior myocardial infarction. Echocardiography showed a thin wall cavity on the apex of the right ventricle. Communication between the left ventricle and the right ventricle was detected on pulsed Doppler echocardiography. Surgery revealed a pseudo-false aneurysm in the free wall of the right ventricle communicating to both ventricles. We emphasize the importance of preoperative morphological and hemodynamic evaluation with Doppler echocardiography in the case of post-myocardial infarction ventricular septal perforation.

Heart Aneurysm↗

Dynamical behavior of psb gene transcripts in greening wheat seedlings. I. Time course of accumulation of the pshA through psbN gene transcripts during light-induced greening.

The time course of the accumulation of the transcripts from 13 psb genes encoding a major part of the proteins composing photosystem II during light-induced greening of dark-grown wheat seedlings was examined focusing on early stages of plastid development (0.5 h through 72 h). The 13 genes can be divided into three groups. (1) The psbA gene is transcribed as a single transcript of 1.3 kb in the dark-grown seedlings, but its level increases 5- to 7-fold in response to light due to selective increase in RNA stability as well as in transcription activity. (2) The psbE-F-L-J operon, psbM and psbN genes are transcribed as a single transcript of 1.1 kb, two transcripts of 0.5 and 0.7 kb and a single transcript of 0.3 kb, respectively, in the dark-grown seedlings. The levels of accumulation of every transcript remain unchanged or rather decrease during plastid development under illumination. (3) The psbK-I-D-C gene cluster and psbB-H operon exhibit fairly complicated northern hybridization patterns during the greening process. When a psbC or psbD gene probe was used for northern hybridization, five transcripts differing in length were detected in the etioplasts from 5-day old dark-grown seedlings. After 2 h illumination, two new transcripts of different length appeared. Light induction of new transcripts was also observed in the psbB-H operon.

Blotting, Northern↗

Clastogenicity of low pH to various cultured mammalian cells.

It has been reported that low pH itself can be clastogenic to Chinese hamster ovary cells or mouse lymphoma L5178Y cells. On the other hand, there was no indication that low pH is clastogenic to rat or human lymphocytes. Therefore, in order to evaluate the generality of clastogenicity of low pH conditions, chromosomal aberration tests were carried out on Chinese hamster cell line cells (CHO-K1, CHL, Don and V79 379A) and human cells (HeLa and peripheral lymphocytes used as whole-blood cultures). The cytotoxicity of low pH to each cell line was also evaluated by counting surviving cells. The treatment medium used was Eagle's MEM containing 15 mM MES or Bis-Tris as an organic buffer to maintain the acidity of the medium for the 6-h or 24-h treatment period, and pH adjustment was done with NaOH or HCl. Chromosomal aberrations were induced at pH 6.5 or below in CHO or CHL cells, and the maximum frequency was 24.7% at pH 6.0 or 34% at pH 6.3, respectively. About 5-10% of Don or HeLa cells had aberrations over the range of pH 6.6-6.0 or pH 6.6-6.3, respectively. In V79 379A cells or human lymphocytes, however, aberrant cells amounted to about 8% at near pH 6.0, where cell survival was low (less than 20%). About 90% of aberrations induced in each cell line examined were chromatid-type gaps and breaks. When CHO or CHL cells were treated with acidic medium for 6 h plus 18 h recovery in fresh medium, about 20% of cells had aberrations including chromatid exchanges at pH 5.5 or pH 5.7, respectively. These results indicate that clastogenicity of low pH is a general finding, although the extent of it varies with cell type, and that the clastogenicity is associated with varying extents of cytotoxicity. The mechanisms of clastogenesis at low pH are not known, but might involve inhibition of DNA or protein synthesis or DNA-repair enzymes.

Animals↗

Identification and characterization of virK, a virulence-associated large plasmid gene essential for intercellular spreading of Shigella flexneri.

Seven virulence loci have been identified by Tn5 insertion mutagenesis on the large 230 kb plasmid (pMYSH6000) of Shigella flexneri 2a. In this study, we used Tn10 insertion mutagenesis and identified a novel virulence locus on pMYSH6000 responsible for bacterial spread. Characterization of the invading bacteria of the Tn10 insertion mutants in the epithelial cells revealed that the bacteria were capable of at least some intracellular spreading but not intercellular spreading. Immunoblot analysis of lysates of the Tn10 insertion mutants with a VirG-specific antipeptide antibody revealed diminished levels of the 116 kDa VirG protein. The virG mRNA in the mutants, however, was expressed at the same level as that in the wild type. The DNA region required for the virulence phenotype was localized to a 1.6 kb DNA sequence in the SalI-K fragment on the plasmid, and thus the locus was designated virK. Expression of virK in Escherichia coli using a T7 RNA polymerase-dependent promoter system yielded a 36 kDa protein. The nucleotide sequence of 1642 bp encoding VirK function was determined, and an open reading frame encoding 316 amino acid residues was shown to encode the VirK protein. The virK region was highly conserved among the large virulence plasmids of shigellae and enteroinvasive Escherichia coli. These results suggest that VirK function is an essential virulence determinant for shigellae involved in the expression of virG gene product at post-transcriptional level.

Amino Acid Sequence↗

Alternatively-spliced p53 mRNA in the FAA-HTC1 rat hepatoma cell line without the splice site mutations.

A novel mutation of the p53 gene has been found in a rat hepatoma cell line, FAA-HTC1. This cell line carried two kinds of abnormal p53 transcripts; one lacked the exon 8 sequence, and the other had a single base substitution G to T which resulted in a new stop codon in exon 8. In the genomic DNA, this base substitution in exon 8 was present, indicating that both transcripts were transcribed from the mutated gene. No mutation was detected in its two flanking introns. In this cell line, the exon-deleted transcript seems to be generated by exon skipping due to an unknown mechanism other than splice site mutations.

Animals↗

[Aortic root reconstruction in the patient with aortic root dissection and aortic valve regurgitation: a case report].

The reported patient was a 60-year-old man with congestive heart failure and recurrent inferior myocardial infarction. The aortogram revealed severe aortic regurgitation, aortic root dilatation and dissection with involvement of the right coronary ostium. Aortic root reconstruction using the valved conduit was performed. The left coronary ostium was reimplanted with Carrel patch method and the right coronary artery was bypassed with the saphenous vein graft. Postoperative course was uneventful and he is asymptomatic in one year after operation. Although aortic root reconstruction with Carrel patch procedure is not widely adopted in Japan, we recommend this procedure because the anastomosis between the coronary ostium and the graft is tight.

Aortic Dissection↗

[A sharp edge of the fractured ribs caused the aortic injury at body-position change: a case report].

The reported patient was a 37-year-old male, who got a blunt chest trauma by a motor vehicle accident. Chest X-ray and computed tomography of the chest revealed bilateral multiple rib-fractures, pneumo-hemothorax, lung contusions, but no evidence of mediastinal hematoma. Since respiratory distress with a flail chest was observed, the patient was placed on an artificial ventilation, and thoracocentesis were also done on both sides, while the hemodynamics was fairly maintained with blood transfusion. On the 10th hospital day, however, he suddenly fell into a deep shock with the left hemothorax by changing the body position. Emergency thoracotomy demonstrated the laceration of the descending aorta, that was considered to be made by the sharp edge of the fractured left 8th rib, which correspondingly protruded into the thoracic cavity toward the aorta. The repair of the aortic injury and the resection of the rib edges were performed. He was discharged on the 45th hospital day. In cases with a blunt chest trauma, the majority of the causes of the traumatic aortic injury are reported to be "deceleration injury". Although the considered mechanism of the traumatic rupture of the thoracic aorta in this case is extremely rare, it should be taken into a consideration for treatment of the cases with a blunt chest trauma and multiple rib-fractures.

Adult↗

[Preoperative hemodilution to reduce homologous blood transfusion--effects on hemodynamics and oxygen flux].

Many problems arise from homologous blood transfusion in operative patients. Preoperative collection of blood with hemodilution is a simple method to allow autologous blood transfusion. Sixty patients who received gynecological operations were divided into three groups. Patients in the first and second groups underwent preoperative blood collection and hemodilution, and collected blood was transfused during operation when bleeding volume had exceeded prefixed value. The volume and speed of blood collection were 20 ml.kg-1 and 30 minutes in the first group, and 20 ml.kg-1 and 15 minutes in the second group. After the collection of blood, HES solution was infused to maintain blood volume. The patients in the third group were transfused with homologous blood as controls. The blood pressure, heart rate, cardiac index and oxygen flux were maintained well in the first group after collection of blood and hemodilution. The hemoglobin concentration was kept at 10 g.dl-1 when the operation was terminated with a mean bleeding volume of 1,014 ml. The results suggest that the method of preoperative blood collection and hemodilution followed by autologous blood transfusion is a promising technic to reduce the amount of homologous blood transfusion in operative patients.

Blood Transfusion, Autologous↗

[Surgical results of two cases of simultaneous surgery of carotid and coronary occlusive disease].

Two cases of symptomatic extracranial carotid artery stenosis associated with ischemic heart disease are reported. The first case was 72-year-old male, who was admitted because of transient ischemic attack due to the stenosis of left internal carotid artery. He had a history of myocardial infarction and coronary angiography revealed three vessel disease. The second case was 74-year-old female with diabetes mellitus. She was admitted because of cerebral infarction. The carotid angiography revealed critical stenosis of bilateral internal carotid arteries. Her coronary angiography revealed three vessel disease. Her chest symptom became unstable after her admission. In both cases, simultaneous carotid endarterectomy and coronary bypass grafting were performed with successful outcome. In the patients with symptomatic extracranial carotid occlusive disease associated with severe ischemic heart diseases, we advocate simultaneous operation both for carotid and coronary artery occlusive disease.

Aged↗

Single sc administration of insulin-like growth factor I (IGF-I) in normal men.

Total and free form of IGF-I in plasma increased in a dose dependent manner after sc IGF-I administration. Peak values of total IGF-I were obtained at 3-4 h after the administration, and then the values decreased gradually. However, peak values of free form of IGF-I were obtained at 2 h, and then rapidly decreased thereafter. The blood glucose, serum insulin and C-peptide levels decreased until 4 h after IGF-I administration in a dose dependent manner. Plasma IGF-II values significantly decreased at 4-12 h after IGF-I administration. Urinary urea nitrogen and sodium excretion decreased after IGF-I administration. Urinary GH excretion also decreased after 0.06 mg/kg IGF-I administration. These data demonstrate that IGF-I may play a role in glucose, protein and electrolyte metabolism, and plasma IGF-II levels and GH secretion might be regulated by IGF-I in man.

Adult↗