[HCV infection among cirrhotic patients as a risk factor for generation of hepatocellular carcinoma: preliminary report].
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Biomedical subjects
Publications and source records attributed to T Nakao.
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From the relationship between the molar ratio of nucleosides calculated stoichiometrically from modified nucleoside occurrences in major RNA species and the proportion of rRNA to all of RNA contents in average tissues, the increase of rRNA contents in cancer tissues growing rapidly was found. Thus, we found that selected urinary modified nucleoside levels were very useful as a biological marker of cancer and AIDS, as well as a good indicator of whole-body metabolic conditions of RNAs.
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Coronary artery bypass grafting using the right gastroepiploic artery and cholecystectomy were simultaneously performed on a 62-year-old woman with both angina pectoris and cholecystolithiasis, with good results being obtained. No case of combined surgery with such coronary bypass has been reported yet. The present simultaneous surgery from our recent experience was regarded as a very useful surgical approach because of only one possible risk of surgical complications such as anesthetic accident, infection, etc, and of easy availability of the right gastroepiploic artery at laparotomy for coronary artery bypass grafting requiring some arterial graft.
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Coronary artery bypass grafting (CABG) was performed in a 67-year-old woman with aortitis. She had a past history of right radical mastectomy. Preoperative coronary angiogram showed diffuse stenotic lesions in both right and left coronary arteries. The pressure gradient between ascending aorta and peripheral radial artery was 90 mmHg and the cause of coronary stenosis seemed to be hypertension due to stenotic distal aorta. The aortogram showed occluded bilateral internal thoracic arteries (ITA) and stenotic abdominal aorta. The cephalic artery was supplied by a large meandering artery via dilated gastroepiploic artery (GEA). And thus the GEA was not useful for CABG. Quadruple CABG was performed with mild varicose saphenous vein (saphenous vein grafts to left anterior descending artery and third branch, and sequential saphenous vein graft to right posterior descending and atrioventricular branches). It seemed to be important to demonstrate the arterial lesion of ITA and GEA before CABG in patients with aortitis.
Modified nucleosides from pooled normal human urine were extracted using a boronate affinity gel column and fractionated by reversed-phase high-performance liquid chromatography (RP-HPLC). The major constituents in each of the 30 RP-HPLC fractions were determined by gas chromatography-mass spectrometry of the trimethylsilyl derivatives of the fractions. The same RP-HPLC method was used in the synthesis of 5'-deoxyxanthosine from authentic 5'-deoxyadenosine. In addition, the simultaneous determination of urinary 5,6-dihydrouridine (D) and pseudouridine (psi) was carried out by RP-HPLC using two ODS columns in series. The level of D in pooled normal urine was 4.87 nmol/mumols creatinine. The RP-HPLC method was applied to the measurement of D and psi levels in urines collected before and after surgery from four patients with gastrointestinal cancer. A large decline in both nucleoside levels in urines after surgery was observed in three of the four cancer patients.
The polymerase chain reaction (PCR) was used to detect hepatitis C virus (HCV) in plasma from chronic non-A, non-B hepatitis patients. By choice of adequate primers, 19 of 24 samples (79%) were found positive. Sequence analysis of amplified 400 bp cDNA fragments encoding a portion of NS5 gene suggested that HCV can be classified into two types (named K1 and K2) in Japan. Slot blot hybridization of the fragments indicated that 13 were HCV-K1 and 6 were HCV-K2, which show 80% and 67% nucleotide sequence homology, respectively, with that of the prototype.
In addition to ganglioside GM1b, an unusual and extremely minor ganglioside, GD1 alpha, was efficiently isolated from bovine brain by combination of Q-Sepharose and Iatrobeads column chromatographies. In the course of purification steps, the presence of the sialidase-labile ganglioside was proved by a highly sensitive TLC/enzyme-immunostaining method. The structure was characterized by gas-liquid chromatography, permethylation study, sialidase degradation, immunostaining with specific antibodies, fast atom bombardment-mass spectrometry, and proton magnetic resonance spectrometry. The content of the ganglioside was very small (0.016%) in the total gangliosides. This finding suggests that a synthetic pathway of asialo GM1----GM1b----GD1 alpha may exist in mammalian brains. A monoclonal antibody NA-6 that was obtained by immunizing mice with purified GM1b reacted specifically with GM1b but showed no cross-reactivity with other structurally related gangliosides such as GM1a, GD1a, and so on. Using the method of TLC/immunostaining with NA-6, GM1b was found to be strongly expressed during embryonic days 14-17 in chick brains. Thus, it is assumed that extremely minor gangliosides like GM1b and GD1 alpha found in adult brains are characterized as embryonic molecules.
An immunohistochemical study was performed to observe cellular proliferation on the surface of implanted intraocular lenses (IOLs) in rabbit eyes. Rabbits were killed at intervals of 3 days and 1, 2, and 4 weeks after the operation. The IOLs were removed and examined by an immunoperoxidase staining method using antifibronectin (anti-FN) antibodies. The FN immunoreactivity was detected in macrophages and giant cells attached to the IOL surface. Prominent staining was observed in these cells 1 week after the operation, and staining for FN was less intense in the specimens obtained 2 and 4 weeks after implantation. These findings suggest that FN is produced by macrophages and giant cells on the IOL surface and may play an important role in cellular adhesion and motility. FN immunoreactivity decreased with time, which might be related to cellular activity.
The major cellular components on intraocular lenses experimentally implanted in the rabbit eye and in the mouse peritoneal space were examined. They consisted of macrophages and their metamorphosed epithelioid cells with occasional formations of foreign-body giant cells from the fusion of the macrophage-related cells. Lymphocytes, individually and in clusters, were also seen on the lenses implanted in the mouse peritoneal space but rarely on those implanted in the rabbit eye. Macrophages, epithelioid cells, and giant cells exhibited active phagocytosis on the implanted intraocular lenses. These cells phagocytized not only minor foreign particles such as artificially fed latex or carbon colloids but also living cells including erythrocytes, leukocytes, and lymphocytes. The nuclear pattern of the giant cell formation process initially assumed a centrally located nuclear distribution of a foreign-body giant cell type, and then a peripherally located Langhans type distribution when the number of nuclei reached about five in both the mouse peritoneal space and the rabbit eye chamber. Ultra-large giant cells containing a number of nuclei, however, were only observed on lenses implanted in the rabbit eye, demonstrating a difference between the two environments.
Three-piece poly(methyl methacrylate) intraocular lenses (IOLs) were implanted in rabbit eyes with and without lens extraction to examine the cellular response on the IOL surface without the effects of the residual lens cortex. Each rabbit had extracapsular lens extraction (ECCE) with IOL implantation in the posterior chamber of one eye. In the second eye, the IOL was implanted in the anterior chamber without lens extraction. The lenses were removed and studied with light microscopy and scanning electron microscopy one week after surgery. Light microscopic findings revealed a similar cellular response on the surface of the IOLs in both groups. Scanning electron microscopy suggested that the cellular adhesiveness on the IOL surface in the eyes without lens extraction was weaker than in the eyes that had ECCE. Cells on the IOLs in the eyes without lens extraction were flatter and had membranous pseudopodia. It appears that the cells on the IOL surface were caused by a foreign body reaction and that their adhesiveness to the IOL was affected by residual lens cortex.
To find out if cows with the downer cow syndrome have enhanced or exhausted adrenocortical function, fifteen downer cows were examined for adrenocortical response to 25 IU of adrenocorticotropic hormone (ACTH) between 1 and 9 days postpartum. Of the 15 cows, only two cows recovered following treatment, 10 cows were slaughtered due to poor prognosis and 3 cows were found dead. Four cows with milk fever also were investigated for adrenocortical function. Both the downer cows and cows with milk fever had significantly higher basal and ACTH-stimulated plasma glucocorticoid concentrations than cows without any postpartum complications on day 1 to 2 postpartum (P less than 0.05). There was a tendency that the downer cows which recovered later did not show enhanced adrenocortical function on day 4 to 5 and day 7 to 9 postpartum, while the downer cows with poor prognosis had significantly enhanced adrenocortical activity on the same days postpartum. The enhanced adrenocortical function shown in the milk fever cows on day 1 to 2 postpartum returned to a nearly normal state after their recovery. The results indicate the downer cows with poor prognosis had greatly enhanced adrenocortical function.
The binding site of a monoclonal antibody, M45-80, against the alpha-subunit of horse Na,K-ATPase was determined. Various sizes of DNA fragments derived from rat Na,K-ATPase alpha 1-subunit cDNA were cloned into pUC19 expression vector and some fragments of horse genomic DNA were cloned into pUC18. Escherichia coli JM83 cells harboring the plasmids were grown and the cell lysates were used as antigens. An enzyme-linked immunosorbent assay revealed that M45-80 recognizes the hexapeptide Glu-Tyr-Thr-Trp-Leu-Glu (which is identical to the rat and horse alpha 1-subunits) at the M3-M4 junction located on the extracellular side. The ouabain-binding site is discussed in relation to the recognition site of M45-80.
A series of 6H-(1)benzothiopyrano[3,4-e][1,2,4]triazolo[4,3- b]pyridazines and 6,7-dihydro-(1)benzothiepino[4,5- e][1,2,4]triazolo [4,3-b]pyridazines were prepared and tested for their ability to displace [3H] diazepam from rat brain membranes. An approximately planar shape of these molecules was essential for high affinity to the benzodiazepine receptor. Among them, 11-aryl compounds in the latter series were found to have high affinity to the benzodiazepine receptor. 11-Phenyl- and 11-thienyl- 6,7-dihydro-(1)benzothiepino[4,5-e][1,2,4]triazolo[4,3- b]pyridazine (3b-5 and 3b-11 respectively) showed the potent affinity comparable to that of diazepam. The structure-activity relationships are also discussed.
A series of 2-substituted-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones and related compounds were synthesized and tested for their ability to displace [3H]diazepam from rat brain membranes. Among them, compounds bearing 4-methoxyphenyl, 4-chlorophenyl, or 4-methylphenyl group at the position-2 were found to have high affinity to the benzodiazepine receptor. 2-(4-Methoxyphenyl)-9-methyl- and 2-(4-methoxyphenyl)-9-methoxy-4,4a,5,6-tetrahydrobenzo[h]cinnolin- 3(2H)-ones (8b-14 and 8b-15, respectively) showed a potent affinity comparable to that of diazepam. These results suggest that a topographical planarity or pseudoplanarity of these molecules is essential for high affinity to the benzodiazepine receptor. The structure-activity relationships are discussed.
A series of 2-aryl-4,4a,5,6-tetrahydropyridazino[4,3-c]quinolin-3(2H)- ones, 2-aryl-4a,5-dihydro-2H-(1)benzothiopyrano[4,3-c]pyridazin-3( 4H)-ones, and related compounds were synthesized and tested for their ability to displace [3H]diazepam from rat brain membranes in vitro, and to prevent bicuculline-induced convulsions in mice in vivo. Among them, 2-(4-chlorophenyl)-4a,5-dihydro-2H-(1)benzothiopyrano[4,3-c]pyr idazin-3(4H)- one (16b) showed remarkable activities both in vitro (Ki 48 nM) and in vivo (ED50 12.4 mg/kg, p.o.). The trans sulfoxide (19a) of 16b exhibited anxioselective pharmacological activities. Compound 19a was equipotent with diazepam in the anticonflict assay (Vogel type, rat, MED 10 mg/kg, p.o.) while exhibiting reduced muscle relaxation (rotarod test) and narcotic potentiation. The structure-activity relationships are discussed.