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Biomedical subjects

H Okazaki

Publications and source records attributed to H Okazaki.

At least 181 records · Page 10Linked to original sources
PubMed1992

Possible involvement of cathepsin L in processing of rat liver hexokinase to eliminate mitochondria-binding ability.

A previously found proteinase possibly involved in the modification of hexokinase to eliminate the mitochondria-binding ability without appreciable change in the catalytic activity (called hexokinase-processing enzyme hereafter), was purified by sequential chromatographies from rat liver and its properties were examined. The hexokinase-processing enzyme had carbohydrate moieties as evidenced by adsorption on immobilized concanavalin A, and had a molecular weight of about 23,000 as estimated by SDS-PAGE and gel filtration chromatography. Benzyloxycarbonyl-phenylalanyl-L-arginine-4-methylcoumaryl-7-amide (Z-Phe-Arg-MCA)-hydrolyzing activity was co-purified with this processing activity throughout the purification, while the hydrolyzing activity for benzyloxycarbonyl-L-arginyl-L-arginine-4-methylcoumaryl-7-amide (Z-Arg-Arg-MCA) was not. The processing activity, as well as Z-Phe-Arg-MCA hydrolyzing activity, was highly sensitive to cysteine proteinase inhibition, for example, by leupeptin and N-[N-3-(trans-carboxirane-2-carbonyl)-L-leucyl]agmatine (E-64). Furthermore, the enzyme preparation reacted with an antibody against cathepsin L purified from rat kidney. These results indicated that cathepsin L may be involved in the above-mentioned processing of hexokinase.

Animals↗
PubMed1992

Hepatocellular carcinoma: treatment with percutaneous ethanol injection and transcatheter arterial embolization.

The therapeutic effectiveness of a new combination therapy--pretreatment with transcatheter arterial embolization (TAE) and subsequent percutaneous ethanol injection (PEI)--for solitary large (> 3.0 cm in diameter) primary hepatocellular carcinoma lesions was compared with that of TAE alone. With TAE alone, a partial response of the tumor was seen in only 10% of the patients, and the 1-, 2-, and 3-year survival rates were calculated to be 68%, 37%, and 0%, respectively. Histologic examination of specimens obtained at hepatectomy showed that TAE alone caused complete necrosis in only 20% of the tumors. In contrast, PEI combined with TAE significantly (P < .05) increased the partial response rate (45%) and significantly (P < .01) prolonged the 1-, 2-, and 3-year survival rates (100%, 85%, and 85%, respectively). Combination therapy caused complete histologic necrosis in 83% of the tumors. It also was significantly (P < .05) better than TAE alone in terms of rate of primary tumor recurrence during follow-up.

Aged↗
PubMed1992

Regulation of platelet-derived growth factor ligand and receptor gene expression by alpha-thrombin in vascular smooth muscle cells.

Since the expression of genes for platelet-derived growth factor (PDGF)-A and PDGF beta-receptor are reciprocally regulated in vascular wall cells after balloon injury, we have investigated the ability of specific vasoactive molecules or growth factors to reproduce the injury pattern of gene expression in cultured rat smooth muscle cells (SMCs) and assessed the effect of inactivating alpha-thrombin on injury-induced expression of PDGF-A mRNA by vascular wall cells in vivo. The molecules investigated, to which vascular SMCs may be locally exposed after mechanical injury, included vasoactive factors (alpha- and beta-adrenergic agonists, serotonin, histamine, angiotensin II, and endothelin) and growth factors (PDGF-AA, PDGF-BB, basic fibroblast growth factor, insulin-like growth factor, epidermal growth factor, and alpha-thrombin). In cultured rat SMCs, only alpha-thrombin (0.1-100 nM), among these compounds, produced the pattern of transiently increased PDGF-A and decreased PDGF beta-receptor mRNA. PDGF-B chain mRNA levels remained undetectable in these cultured SMCs. The dependence of these changes in gene expression on the proteolytic activity of alpha-thrombin was shown by the interruption of altered gene expression or DNA synthesis after incubating the cultured SMCs with covalently inactivated alpha-thrombin using D-Phe-Pro-Arg chloromethyl ketone, a synthetic direct active-site irreversible inhibitor of alpha-thrombin. Continuous intravenous infusion of this synthetic antithrombin into baboons for 6 hours (100 nmol/kg per minute maintaining constant plasma levels of 3.0 +/- 0.5 microns/ml) after inducing balloon-catheter arterial injury also prevented the threefold increase in expression of PDGF-A mRNA characteristically exhibited by untreated mechanically injured vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1992

Structures of americanol A and isoamericanol A having a neurotrophic property from the seeds of Phytolacca americana.

The structures of new neo-lignans, isoamericanol A (1) and americanol A (2) isolated from the seeds of Phytolacca americana have been elucidated on the basis of spectroscopic data and then confirmed by chemical correlation with the previously known isoamericanin A (3) and americanin A (4). Isoamericanol A, americanol A, and americanin A have been found to enhance choline acetyltransferase activity at 10(-5) M in a cultured neuronal cell system derived from fetal rat hemisphere.

Animals↗
PubMed1992

Renal potassium wasting in distal renal tubular acidosis: role of aldosterone.

The pathogenesis of renal potassium wasting and hypokalemia in classic renal tubular acidosis (type 1 RTA) remains uncertain. The prevailing theory is that K(+)-Na+ exchange is stimulated due to an inability of the distal tubule to establish a normal steep lumen-peritubular H+ gradient. We encountered a 42-year-old woman with type 1 RTA associated with Sjögren's syndrome, in whom renal potassium wasting and hypokalemia persisted despite sustained correction of systemic acidosis with alkali therapy and increased intake of potassium. In addition, plasma renin activity was markedly increased and the serum aldosterone level was upper-normal despite the hypokalemia. Increased intake of sodium resulted in suppression on the serum aldosterone and correction of renal potassium wasting and hypokalemia. This case shows that secondary hyperaldosteronism, possibly due to an impairment of sodium conservation in the distal tubule, may contribute to the loss of potassium from the distal tubule even after the correction of acidosis.

Acidosis, Renal Tubular↗
PubMed1991

Reduced D2 dopamine and muscarinic cholinergic receptor densities in caudate specimens from fluctuating parkinsonian patients.

Binding of spiperone and 3-quinuclidinyl benzilate (QNB), both labeled with hydrogen 3 (3H), were measured in caudate tissue obtained from 8 living parkinsonian patients at the time of cerebral transplantation. This was clinically homogeneous group of patients. All remained predominantly responsive to levodopa, although with marked disability secondary to clinical fluctuations (short-duration responses) and medication-induced dyskinesias; all were receiving substantial doses of levodopa and 6 of the 8 patients were additionally receiving bromocriptine or pergolide. Binding densities of dopamine D2 receptors, as measured by [3H]spiperone binding, were reduced in this group of patients, compared to caudate specimens from autopsy control subjects. This findings may reflect medication-induced receptor downregulation. Parallel changes occurred with muscarinic cholinergic receptors; [3H]QNB binding was significantly reduced, compared to autopsy control values. This reduction of muscarinic receptors might be due to loss of nigrostriatal terminals that are known to contain muscarinic receptors. Alternatively, muscarinic receptors may have been downregulated by increased corticostriatal glutamatergic input to cholinergic cells, inferred to be present based on the prominent levodopa-induced dyskinesias. Finally, receptor deficits could have been a reflection of more widespread degenerative cerebral disease, although levodopa-refractory symptoms were generally not pronounced in these patients.

Adult↗
PubMed1991

Platelet-activating factor detected in bronchoalveolar lavage fluids from an asthmatic patient.

It recently has been recognized that platelet-activating factor (PAF) may be a mediator of asthma exacerbation. We had the opportunity to analyze bronchoalveolar lavage fluids from an asthmatic infant, which were characterized by neutrophil infiltration. The patient's lungs were washed on three occasions with saline during asthmatic attacks. PAF was found in each case on the basis of its ability to cause the immediate aggregation of washed rabbit platelets. The PAF detected was equivalent to 1-1.4 pmol of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine, three quarters of which were recovered in cell-associated form. By contrast, we did not detect PAF in bronchoalveolar exudates from patients with laryngeal stenosis or with respiratory distress syndrome. LysoPAF, the direct precursor as well as initial metabolite of PAF, was also analyzed after being converted to PAF by acetylation. There was a wide variation in the amount of lysoPAF present in individual patients, suggesting that lysoPAF levels cannot be taken as an indicator for the presence of PAF.

Asthma↗
PubMed1991

Acute effects of intravenous propafenone on the internal ventricular defibrillation threshold in the anesthetized dog.

In 10 treated and 2 control dogs, the short-term effects of intravenous propafenone (2 mg/kg/10 minutes, followed by 1 mg/min [n = 2] or 25 micrograms/kg/min [n = 8]) on the internal ventricular defibrillation energy requirements (DER) were investigated. Multiple stored energy levels were randomly tested and the percent successful defibrillation was plotted against the stored energy, and the raw data were fit by logistic regression. The energy at 50% (E50) and 80% (E80) defibrillation success increased after propafenone by a mean of 75% (8.4 +/- 2.4 to 14.7 +/- 5.9 joules, p less than or equal to 0.05) and 59% (11.1 +/- 3.5 to 17.6 +/- 6.7 joules, p less than or equal to 0.05), respectively. Plasma propafenone levels ranged from 778 to 2554 ng/ml (1495 +/- 592 ng/ml) at the beginning to 833 to 2193 ng/ml (1297 +/- 389 ng/ml) at the end of the defibrillation trials. Two dogs served as controls and received Ringer's solution instead of propafenone and showed the temporal stability of the preparation. In conclusion, intravenous propafenone increases the internal ventricular DER in this canine model. This may have important clinical implications in patients with automatic implantable cardioverter-defibrillators (AICDs) receiving concomitant antiarrhythmic drug therapy and in patients undergoing therapy with intravenous propafenone.

Animals↗
PubMed1991

Intracranial cerebrovascular vasa vasorum associated with atherosclerosis and large thick-walled aneurysms.

Atherosclerotic plaques that develop in the extracranial circulation are usually extensively vascularized by vasa vasorum. However, human vasa vasorum associated with intracranial atherosclerosis has not been adequately addressed. Anterior and posterior circulation specimens from fresh autopsy material were studied under the magnification of a dissecting microscope and proliferative vasa vasorum was found to be frequently associated with intrinsic atheromatous plaques. Vasa vasorum associated with an incidental large aneurysm supports the radiological literature demonstrating that many large and giant thick-walled aneurysms exhibit vascularized walls on contrast computed tomography scans. This information may aid in the preoperative assessment and possible repair of these aneurysms.

Adolescent↗
PubMed1991

High-level secretion of human apolipoprotein E produced in Escherichia coli: use of a secretion plasmid containing tandemly polymerized ompF-hybrid gene.

A gene encoding the mature form of human apolipoprotein E (h-apoE) was fused to the secretion signal coding sequence of the Escherichia coli major outer membrane protein F (ompF) which was preceded by a consensus Shine-Dalgarno sequence. Two copies of this hybrid gene were inserted tandemly into an expression vector and expressed in E. coli under the transcriptional control of two tac promoters regulated by lac repressors. By the addition of isopropyl-beta-D-thiogalactopyranoside (IPTG) to the growth media, cells synthesized h-apoE at the level of 27.2 micrograms per A600 and up to 22% of the total cellular protein. The h-apoE produced by E. coli was processed precisely, secreted into the periplasmic space and formed protein aggregates there. However, despite aggregation, they were easily dissolved in water and actively formed protein-lipid complexes with dimyristoyl phosphatidyl choline (DMPC). These results demonstrated that E. coli cells are able to synthesize and secrete a large amount of active h-apoE using a prokaryotic signal sequence.

Amino Acid Sequence↗
PubMed1991

High-molecular-weight Ly-5 isoforms expressed on T cells: activation-dependent expression.

Interleukin 2 (IL-2)-dependent granular T lymphocyte (GTL) lines derived from murine spleen were shown to express a Ly-5 antigen with the so-called 'B220-epitope' recognized by 6B2 mAbs, which were normally exhibited on B-lineage cells. Immunoprecipitation analysis revealed that the Ly-5 isoform on GTL lines represented the highest-molecular-weight Ly-5 so far described (260 kd), distinct from the B220 isoform on a pre-B cell line (240 kd). The size difference between them was also evident after the endoglycosidase treatment (210 versus 190 kd), strongly suggesting that these Ly-5 isoforms had core proteins of distinct size. Sequential immunoprecipitation by 6B2 and 14.8 mAbs further indicated that the 260 kd Ly-5 on GTL lines predominantly expressed '6B2 epitope' while '14.8 epitope' dominated in the B220 (240 kd) on a pre-B cell line. Northern blot analysis of the Ly-5 transcripts using probes for the known alternative exons failed to show any evidence for mRNA of the 260 kd Ly-5 distinct from that of B220. Polymerase chain reaction analysis, however, suggested that the 260 kd isoform mRNA might be transcribed from a distinct promoter with a yet undefined exon(s). The 6B2+ Ly-5 isoform was hardly detected on normal splenic T cells, but was shown to be induced rapidly on the majority of T cells following IL-2 stimulation in vitro, indicating that this particular Ly-5 isoform behaved as an 'activation antigen' on T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Hepatocellular carcinoma: treatment with a combination therapy of transcatheter arterial embolization and percutaneous ethanol injection.

In an attempt to obtain complete tumor necrosis in large hepatocellular carcinoma (HCC) lesions, the authors studied the clinical and histologic findings of a new combination therapy, percutaneous ethanol injection (PEI) with transcatheter arterial embolization (TAE) (pretreatment with TAE and subsequent PEI) in 15 patients with a single, large (3.0-9.0 cm in diameter), encapsulated lesion of HCC. Two weeks after TAE, PEI was performed under ultrasound guidance. A total of four to 11 injections were administered at a rate of one injection twice a week. During the follow-up period (range, 7-23 months), all lesions were reduced in size and no evidence of HCC was present at contrast material-enhanced computed tomography or angiography in nine of 11 patients who did not subsequently undergo surgery. Six patients had a follow-up of 1 year or more, for a 1-year survival rate of 100%. Four patients subsequently underwent surgical resection; complete necrosis of the tumor was observed in all four. The authors conclude that a combination of PEI and TAE is an appropriate treatment for patients with large, encapsulated HCC lesions who are poor surgical risks.

Aged↗
PubMed1991

Multiple sclerosis: histopathologic and MR and/or CT correlation in 37 cases at biopsy and three cases at autopsy.

The authors retrospectively reviewed the cases of 40 patients with biopsy- or autopsy-proved inflammatory demyelination consistent with multiple sclerosis (MS); each patient underwent magnetic resonance (MR) and/or computed tomographic (CT) imaging. In review of the 32 MR and 30 CT examinations, three predominant radiologic patterns were apparent: (a) relatively small homogeneous lesions with no or minimal diffuse enhancement; (b) hypoattenuating lesions on CT scans and hypointense lesions on short-TR MR images, with a contrast material-enhanced, isoattenuating or isointense ring; and (c) lesions that were more infiltrative and ill defined, with mixed attenuation and signal intensity and scattered enhancement. A common radiologic feature was lack of mass effect or edema in white matter surrounding even large lesions. In all but four patients the lesions were classified as active by using both histologic and clinical criteria. Histologically active lesions had various radiologic appearances; however, in all contrast-enhanced studies they demonstrated some form of enhancement. Inactive lesions were homogeneously hypoattenuating on CT scans, hypointense on short-TR MR images, and hyperintense on unenhanced, long-TR MR images.

Adolescent↗
PubMed1991

Effect of experimental ocular hypertension on macrovacuolation in Schlemm's canal endothelial cells of monkey eyes.

The severance of all the extraocular muscles (tenotomy) caused temporary ocular hypertension, lasting a few days, in Japanese monkey (Macaca fuscata) eyes. We studied the morphology of Schlemm's canal endothelium of the eyes under a light microscope after quick fixation through continuous irrigation of the anterior chamber with a 10% acrolein solution, with precise control of the hydrostatic pressure on the eyes during fixation. A statistically significant increase in macrovacuolation in endothelial cells of Schlemm's canal of normal eyes was observed when additional hydrostatic pressure was applied. However, such an increase was not observed in the case of tenotomized temporary hypertensive eyes.

Animals↗
PubMed1991

Amphiphile-induced erythrocyte shape change and simultaneous tetraethylammonium ion uptake.

Amphiphile-induced tetraethylammonium ion (TEA+) uptake into human erythrocytes was examined along with cell shape change. A TEA(+)-sensitive electrode was used to determine the amount of uptake. TEA+ was preferentially incorporated into erythrocytes when amphiphiles changed cell shape to an invaginated form. This was contrasted with the release of acetylcholinesterase outside cells which occurred markedly with the amphiphiles, causing the crenated form. It was suggested that the invagination of erythrocyte membrane stimulated the formation of vacuoles, in which TEA+ existing in an external medium was entrapped.

Erythrocyte Deformability↗
PubMed1991

TAN-931, a novel nonsteroidal aromatase inhibitor produced by Penicillium funiculosum No. 8974. I. Taxonomy, fermentation, isolation,characterization and biological activities.

A novel nonsteroidal aromatase inhibitor, TAN-931, was isolated from the culture filtrate of a soil isolate fungus, No. 8974. The strain was identified as Penicillium funiculosum No. 8974. TAN-931 inhibited human placental and rat ovarian aromatase activity, and the IC50 value was 17.2 and 162 microM, respectively. The inhibition of human placental aromatase was uncompetitive with respect to androstenedione conversion with a Ki value of 40 microM. When TAN-931 was subcutaneously administered at doses of 25, 50 and 100 mg/kg (once/day, x4) to 20-day-old female Sprague-Dawley rats treated with gonadotropin, the plasma estradiol-17 beta level and the weight of ovaries and uterus were markedly reduced in a dose-dependent manner. The in vivo inhibitory activity of TAN-931 was more potent than that of 4-hydroxyandrostenedione. Consecutive administration of TAN-931 (100 mg/kg, sc, twice/day, x 7) to 9-week-old male Sprague-Dawley rats did not induce any adrenal hypertrophy even though administration of aminoglutethimide caused 2-fold enlargement of the adrenal under the same conditions. Specific binding of TAN-931 to the estrogen receptor from a human breast cancer cell line, MCF-7, was not detected.

Adrenal Glands↗