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Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 19 recordsLinked to original sources

Partially folded state of the disulfide-reduced form of human serum albumin as an intermediate for reversible denaturation.

The conformation of the fully disulfide-reduced state of human serum albumin was investigated by tryptophan fluorescence spectrum, CD analyses, and size-exclusion chromatography. Both the reduction of the native disulfide-bonded form under nondenaturing conditions and the refolding of the urea-denatured disulfide-reduced form under reduced conditions yielded almost exactly the same disulfide-reduced state with partially folded unique conformation that was clearly distinguished from either the native or fully denatured state. In addition, the interconversion between the urea-denatured reduced form and the partially folded reduced form was reversible with each other; by reoxidation, the partially folded reduced form was converted to the disulfide-bonded form. The conformation of disulfide-reduced serum albumin was highly variable depending on pH and ionic strength conditions. Thus, we concluded that the disulfide-reduced state with partially folded variable conformation is involved in the reversible interconversion between the denatured reduced form and the native disulfide-bonded form of human serum albumin.

Chromatography, Gel

Reversible denaturation of disulfide-reduced ovalbumin and its reoxidation generating the native cystine cross-link.

The authors in a previous report (Klausner, R. D., Kempf, C., Weinstein, J. N., Blumenthal, R., and van Renswoude, J. (1983) Biochem. J. 212, 801-810) have argued that native folding of ovalbumin occurs during translation, but not in a renaturation system of the denatured form. To re-examine the possibility, we searched for the conditions of correct oxidative refolding of denatured disulfide-reduced ovalbumin. Data of trypsin resistance, CD-spectrum, and selective reactivity of cysteine sulfhydryls revealed that the fully denatured protein can refold into the native conformation under disulfide-reduced conditions. The interconversion between the native and denatured forms was fully reversible with a free energy change for unfolding of 6.6 kcal/mol at 25 degrees C. Subsequent reoxidation under a variety of redox conditions generated only one disulfide bond in the reduced refolded protein with six cysteine sulfhydryls. Furthermore, the regenerated disulfide was found by peptide analyses to correspond to the native disulfide pairing, Cys73-Cys120. We, therefore, concluded that co-translational folding, if any, is not requisite for the correct oxidative folding of ovalbumin.

Amino Acid Sequence

[Evaluation of transcatheter arterial embolization with coaxial microcatheter and micro-coil for vascular lesions].

Transcatheter arterial embolization using a coaxial microcatheter and micro-coil was performed in eight patients with vascular lesions; one each with aneurysm of the basilar artery, cerebellar artery, and pancreatic artery, pseudoaneurysm of the common hepatic artery, gastroduodenal artery, and gluteal artery, carotid-cavernous fistula, and thoracic paraspinal arteriovenous malformation. Complete occlusion was achieved in five patients with aneurysm and pseudoaneurysm by occluding the aneurysmal cavity and/or the orifice. A patient with recurrent carotid-cavernous fistula was also completely embolized. A case of basilar artery aneurysm resulted in partial occlusion because the posterior cerebral artery originated from the aneurysm. The unsatisfactory result in a case of paraspinal AVM was due to its wide extension with multiple feeding arteries. No apparent complication was seen. In conclusion, super-selective arterial embolization therapy with coaxial microcatheter and micro-coils was found to be a useful method for vascular lesions that would have been technically difficult to embolize with the standard catheter and coils.

Adult

Reversibility of catechol-induced rat glandular stomach lesions.

The potential reversibility of glandular stomach lesions induced by the clastogen, catechol, was examined in groups of male F344 rats treated continuously with 0.8% catechol in the diet for 12, 24, 48, 72, or 96 weeks. After a return to basal diet for 84, 72, 48, 24, and 0 weeks, respectively, the animals were killed for histopathological examination. Incidences of submucosal hyperplasia, adenomas and adenocarcinomas, average number of tumors per rat, and the size of tumors in rats treated with catechol for 12, 24, 48, 72, and 96 weeks increased time dependently. After cessation of catechol treatment, although average number of tumors per rat slightly decreased, the size of tumors tended to increase. Labeling indices in both tumorous and nontumorous areas decreased after cessation of catechol treatment. The results thus indicate that whereas some submucosal hyperplasias or adenomas may regress, others have the potential to develop into adenomas or adenocarcinomas. However, tumor growth does depend to a certain extent on continued catechol treatment.

Adenocarcinoma

Influence of CRT workstation on observer's performance.

The effects of the operability of the prototype CRT workstation and room illumination upon observer's performance were studied. In the experiment of reading CT images as a routine daily work at the CRT workstation, the average time required to analyse one CT image under a room illuminance of 100 lux was longer than that on the film viewbox. Prolongation occurred due mainly to the longer time required to retrieve and to arrange images as observers desired, and the limitation to the number of images simultaneously displayed on two CRT monitors. In the ROC studies to detect small pulmonary nodules on CRT images of computed radiography with imaging plate, illuminance around 170 lux showed the best result and a statistically significant difference (P less than 0.05) as compared with that of 480 lux. In addition to the radiologist's visual performance, room illumination must also be taken into consideration as it influences the observer's performance and diagnostic efficiency.

Computer Systems

Influence of caffeic acid and other o-dihydroxybenzene derivatives on N-methyl-N'-nitro-N-nitrosoguanidine-initiated rat forestomach carcinogenesis.

Promotion effects of the o-dihydroxybenzene derivatives, protocatechuic acid (PCA), dopamine hydrochloride (DAH), dl-dopa and caffeic acid on forestomach and glandular stomach carcinogenesis were investigated in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Groups of 20 male F344 rats were given a single intragastric administration of 150 mg/kg body wt MNNG and starting 1 week later than received diet containing 1.5% PCA, 1.5% DAH, 1.5% dl-dopa or 1% caffeic acid or basal diet alone for 51 weeks and then killed. Other groups of 10-15 rats were given PCA, DAH, dl-dopa or basal diet alone without the MNNG pretreatment. On histological assessment, the incidences of forestomach papillomas and squamous cell carcinomas were significantly enhanced in the group treated with caffeic acid (95 and 100%) as compared with the control values (35 and 10%). Although the incidence was not different, the number of papillomas per rat in the group given DAH (0.79 +/- 0.79) was also significantly increased (0.35 +/- 0.49). PCA and dl-dopa treatments did not modify the development of neoplastic lesions in the forestomach epithelium to any significant extent. None of the four chemicals enhanced glandular stomach carcinogenesis. The results thus demonstrated that whereas caffeic acid and DAH respectively, exert strong and weak promotion activity for rat forestomach carcinogenesis this promotion potential is not shared by all dihydroxybenzene derivatives. An influence of substituents in the para position in addition to the o-dihydroxy moiety is indicated.

Adenocarcinoma

Enhancing effects of diallyl sulfide on hepatocarcinogenesis and inhibitory actions of the related diallyl disulfide on colon and renal carcinogenesis in rats.

It has been reported that diallyl sulfide (DS) and diallyl disulfide (DDS), major volatile compounds in garlic (Allium sativum), exert anticarcinogenic activity in several organs in rodents. The modifying effects of these two chemicals were therefore assessed using two-step liver and multi-organ carcinogenesis models. In experiment 1, male F344 rats were given a single i.p. injection of N-diethylnitrosamine (200 mg/kg body wt) and then received DS or DDS by intragastric intubation at doses of 200 and 50 mg/kg body wt, respectively, three times a week for 6 weeks. All rats were subjected to two-thirds partial hepatectomy at experimental week 3. In experiment 2, male F344 rats were sequentially treated with five carcinogens with different organ target sites for 4 weeks, and then administered DS or DDS as in experiment 1 for 24 weeks. DS demonstrated clear enhancing effects on the development of glutathione S-transferase placental form positive foci in both experiments. On the other hand, an inhibitory potential in colon and renal carcinogenesis was observed in rats treated with DDS. Therefore, while DDS may act as a chemopreventive agent, DS may promote hepatocarcinogenesis.

Allyl Compounds

Three-dimensional structure of soybean beta-amylase determined at 3.0 A resolution: preliminary chain tracing of the complex with alpha-cyclodextrin.

The three-dimensional structure of a complex of soybean beta-amylase [EC 3.2.1.2] with an inhibitor, alpha-cyclodextrin, has been determined at 3.0 A resolution by X-ray diffraction analysis. Preliminary chain tracing showed that the enzyme folded into large and small domains. The large domain has a (beta alpha)8 super-secondary structure, while the smaller one is formed from two long loops extending from the beta 3 and beta 4 strands of the (beta alpha)8 structure. The interface of the two domains together with shorter loops from the (beta alpha)8 structure form a deep cleft, in which alpha-cyclodextrin binds slightly away from the center. Two maltose molecules also bind in the cleft. One shares a binding site with alpha-cyclodextrin and the other is situated more deeply in the cleft.

Binding Sites

Mechanism underlying the changes in plasma potassium concentration during infusion of isosmotic nonelectrolyte solution.

Generally, during infusion of an isosmotic nonelectrolyte solution that permeates the cell membrane, plasma K+ concentration ([K+]pl) either does not change or it increases slightly. The mechanism underlying this [K+]pl change has not been clarified. We continuously monitored the [K+]pl and plasma Na+ concentration ([Na+]pl) for 10 min during isosmotic mannitol infusion of 1.6 ml/100 g body weight in rats with intact kidney function (intact mannitol group). In addition, in nephrectomized rats, we compared the [K+]pl change during infusion with isosmotic mannitol (which permeates the cell membrane; mannitol nephrectomized group) with that during infusion with isosmotic sucrose (which does not permeate the cell membrane; sucrose nephrectomized group) to evaluate the effect of cell volume regulation. In the intact mannitol group, [Na+]pl decreased with dilution, and [K+]pl remained relatively constant. In the sucrose nephrectomized group, [K+]pl decreased by the same percentage as [Na+]pl and gradually increased to greater than the control level. In the mannitol nephrectomized group, however, [K+]pl increased immediately after the beginning of the infusion and reached the same level as that in the sucrose nephrectomized group. To confirm that the difference in [K+]pl between the mannitol and sucrose nephrectomized groups was dependent on cell volume regulation, we investigated the changes in mean corpuscular volume of red blood cells, using a Coulter counter. This value remained constant during isosmotic sucrose infusion but increased during isosmotic mannitol infusion, returning to the original volume after the infusion. We kept [HCO3-] and pH constant throughout the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Suppression of diethylnitrosamine-initiated preneoplastic foci development in the rat liver by combined administration of four antioxidants at low doses.

Potential synergism between 4 antioxidants acting at low doses on development of glutathione S-transferase placental form (GST-P)-positive liver cell foci was examined in male rats initially given diethylnitrosamine (200 mg/kg, i.p.). Beginning 2 weeks after the initiation, rats received the antioxidants, individually or in combination, in the diet for 6 weeks. All rats were subjected to two-thirds partial hepatectomy at week 3 and killed at week 8. The numbers and areas of GST-P-positive foci were significantly decreased by single treatment with butylated hydroxyanisole (BHA, 1%), tert-butylhydroquinone (TBHQ, 1%) and catechol (0.8%), but not with sesamol (0.5%). Combined treatments (BHA + TBHQ, catechol + sesamol, or all 4 chemicals) at a quarter of the above dose levels resulted in decrease in numbers and areas of foci to levels less than the sums of individual inhibition data obtained with the one-quarter levels. Although these combined effects were not statistically significant in the additive model, the results indicate possible synergistic suppression of carcinogenesis by low-dose combined treatment with anti-cancer agents and the usefulness of the present protocol for this type of analysis.

Animals

The modifying effects of indomethacin or ascorbic acid on cell proliferation induced by different types of bladder tumor promoters in rat urinary bladder and forestomach mucosal epithelium.

The effects of indomethacin (IM) or L-ascorbic acid (AsA) on cell proliferation induced by bladder tumor promoters such as butylated hydroxyanisole (BHA), sodium L-ascorbate (Na-AsA), sodium citrate (Na-Cit), and diphenyl (DP) in rat bladder and forestomach epithelium were investigated. Treatment with IM in combination with BHA or Na-AsA diminished DNA synthesis levels of bladder epithelium as compared to the BHA or Na-AsA alone values. On the other hand, AsA further amplified the increase of bladder epithelial DNA synthesis caused by Na-Cit treatment. Histopathologically, administration of Na-AsA in combination with IM reduced the incidence of simple hyperplasia. In contrast, simultaneous treatment with Na-Cit and AsA caused an increase of the hyperplasia development. No apparent combination effects were observed in the DP-treated groups. In forestomach epithelium, AsA enhanced the BHA-induced increase in DNA synthesis and epithelial hyperplasia, characterized by marked basal cell proliferation. The present results thus suggested that IM may exert inhibitory effects on promotion of bladder carcinogenesis by certain tumor promoter types, and AsA may enhance BHA forestomach carcinogenesis.

Animals

Forestomach neoplasm induction in F344/DuCrj rats and B6C3F1 mice exposed to sesamol.

Sesamol was administered at a dietary level of 2% to groups of 30 male and female F344/DuCrj rats and B6C3F1 mice for 104 and 96 weeks, respectively. Squamous cell carcinomas in the forestomach were induced in nine of 29 (31%) effective male rats, three of 30 (10%) female rats, eleven of 29 (38%) male mice and five of 30 (17%) female mice treated with sesamol. Papillomas developed in ten of 29 (34%) male rats and fourteen of 30 (47%) female rats, but not in any of the mice. Hyperplasias developed in almost all rats and mice of both sexes. Significant differences from control values were found for all three lesions in rats and for carcinoma and hyperplasia categories in mice. The incidences of other tumors in the 2% sesamol group were comparable with control values. In conclusion, sesamol induces squamous cell carcinomas in the forestomach of rats and mice, males being more susceptible than females.

Animals

Elevated mean systemic filling pressure due to intermittent positive-pressure ventilation.

To clarify the effect of intermittent positive-pressure ventilation (IPPV) on systemic circulation, mean systemic filling pressure (Psf) and circulating blood volume were measured together with other hemodynamic parameters of capacitance vessel. Change in circulating blood volume was determined by dilution with 51Cr-labeled erythrocytes. Vascular compliance (Cvas) was measured from the change in Psf caused by a bolus injection of blood. These parameters were measured during both spontaneous respiration and IPPV in male Wistar rats anesthetized with pentobarbital sodium. The shift from spontaneous respiration to IPPV reduced cardiac output (CO) by 20.9%. Psf increased significantly, from 7.1 +/- 1.2 to 8.6 +/- 1.1 mmHg. Central venous pressure (Pcv) also increased significantly. The pressure gradient for venous return decreased by 15.6% (from 6.4 to 5.4 mmHg). The resistance to venous return did not change significantly, but there was a significant increase in total peripheral resistance. Neither Cvas nor circulating blood volume was changed significantly by IPPV. These results indicate that during IPPV the increased Pcv attenuates the pressure gradient for venous return and decreases CO and that the compensatory increase in Psf is caused by a blood shift from unstressed to stressed blood volume.

Animals

Dose-dependent renal tubular toxicity of harman and norharman in male F344 rats.

The renal toxicity of harman and norharman, administered for 2 or 4 weeks at dietary levels of 1,000, 500, or 0 parts per million (ppm), was investigated in 6-week-old male F344/DuCrj rats. Although rats fed 1,000 ppm harman or norharman, but not the 500 ppm level, demonstrated marked body weight retardation from 1 week to termination, no mortalities occurred. Marked elevation of water consumption was evident in rats given harman or norharman at 1,000 ppm, but not at 500 ppm, together with large increases in urine of low specific gravity. Urinary lysosomal enzymes (N-acetyl-beta-D-glucosaminidase, NAG, and lactate dehydrogenase, LDH) and sugar levels were increased, and the brush border enzymes (gamma-glutamyl transpeptidase, GGT, and alkaline phosphatase, ALP) decreased. Furthermore, serum biochemistry revealed clear elevation of parameters indicating renal toxicity in these rats. Histopathologically, rats fed 1,000 ppm harman or norharman, but not 500 ppm, demonstrated focal toxic renal degenerative/necrotic and regenerative lesions in proximal, distal, and collecting tubules. These changes were associated with a clearly increased labeling index (LI) of the nuclei of renal tubular epithelial cells on immunohistochemical staining for 5-bromo-2'-deoxyuridine (BrdU). Chemical specific crystal formation within tubular lumina was evident in rats fed 1,000 ppm, but not 500 ppm, this being considered the cause of the renal tubular lesions. It was concluded that harman and norharman exert renal toxicity at the dietary level of 1,000 ppm, but not 500 ppm, in male F344 rats.

Acetylglucosamine

Biphasic change in plasma potassium concentration by mannitol infusion in rats.

Changes in plasma Na+([Na+]pl) and K+([K+]pl) concentrations were continuously measured in nephrectomized rats consequent to intravenous infusion of isosmotic mannitol (M group) or sucrose (S group) at 1.6 ml/100 g body wt. for 10 min, and for the following 30 min. The effect of a Ca2+ channel blocker (diltiazem, 0.1 mg/100 g body wt.) was also evaluated. In the S group, [K+]pl decreased during the infusion and rose above the control level after the discontinuance of infusion. In the M group, [K+]pl gradually increased even during the infusion and reached the same level as the S group at the end of the experiment. In both the S and M groups, [Na+]pl decreased, while PaCO2, pH, and HCO3- did not change. The increase in [K+]pl in the M group had two components. The first was a transient component as presented by the difference of [K+]pl between the M and S group. It might be attributable to K+ release from the intracellular space during a regulatory volume decrease consequent to cell swelling induced by isosmotic mannitol infusion. The second component of the increase in [K+]pl after the infusion was observed in both groups, and this increase might be related to the dilution of ions induced by the large amount of infused nonelectrolyte solution. Diltiazem suppressed both of these changes in [K+]pl, suggesting that they are related to Ca2+ channels. The results suggest that increase in [K]pl by isosmotic mannitol infusion is related to the effects of regulatory volume decrease and dilutional effect.

Animals