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Biomedical subjects

H Utsumi

Publications and source records attributed to H Utsumi.

At least 91 records · Page 5Linked to original sources

In vivo ESR studies of antioxidant activity on free radical reaction in living mice under oxidative stress.

In vivo antioxidant activity seems to be quite complicate due to multiple interaction with biomaterials and differs from results by in vitro experiments. In vivo estimation of antioxidant activity is performed by measuring TBA reactive substances in blood or hydrocarbon gases in breath, but these systems do not measure free radical reaction but the final products of oxidative reaction. In the present study, we applied in vivo ESR to evaluate antioxidant activity by monitoring the redox reaction of nitroxide radical and clearly found that the nitroxide is very susceptible to oxidative stress in vivo and quite useful to evaluate antioxidant activity non-invasively.

Animals↗

[A 71-year-old woman with progressive gait disturbance and dementia].

We report a 71-year-old woman with progressive gait disturbance and dementia. The patient was well until 61 years of age (1980) when she noted a gradual onset of gait disturbance. A year later, she noted slurring of the speech and forgetfulness. In 1982, she noted difficulty in looking down and progression of her gait disturbance. In 1983, she became unable to walk alone unless supported. She was admitted to our service in 1984; neurological examination at that time revealed moderate dementia, limitation in the vertical gaze, slurred speech, and wide based ataxic gait. She was discharged for out patient follow up. Cranial CT scan in 1989 revealed cortical, brain stem, and cerebellar atrophies. On March 10, 1990, she fell down and hit her head. She developed headache on April 1, vomited on April 8, and was admitted to our service again. On admission, she was somnolent, she was unable to follow an object to any direction; oculocephalic response was elicited to horizontal directions, however, it was difficult to induce in the vertical direction. Rigidity was noted in the extremities except in the left lower extremity. Rapid alternating movement was difficult and dysmetria was noted in the finger-to nose test. Deep reflexes were exaggerated without clonus; the plantar response was extensor bilaterally. Cranial CT scan revealed bilateral subdural hematoma. She was treated with intravenous infusion of glycerol, and she became alert after this treatment; however, she was markedly demented. She was unable to walk alone. She was discharged to home, but she showed progressive loss of activities, and became bed ridden in December 1992. In January of 1993, she developed fever, dyspnea, and disturbance of consciousness, and was admitted again on January 26, 1993. On admission, her blood pressure was 70 mmHg by palpation and body temperature 38.5 degrees C. The lungs were clear. On neurologic examination, she was semicomatose; the optic fundi were unremarkable; only incomplete eye movements elicited by the oculocephalic reflex. She was passive supine in position; some spontaneous movements were observed in the extremities. Lead-pipe rigidity was noted in both upper extremities, but the muscle tone was decreased in the lower extremities. No abnormal involuntary movements were seen. Deep reflexes were exaggerated except for the ankle jerk which was diminished bilaterally. The plantar response was extensor on both sides.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Inhibitors of poly (ADP-ribose) synthesis inhibit the two types of repair of potentially lethal damage.

PURPOSE: The purpose of this study was to examine whether 3-amino-benzamide (3ABA), an inhibitor of poly (ADP-ribose) synthesis, inhibits the two types of potentially lethal damage (PLD) repair, termed slow and fast. METHODS AND MATERIALS: The fast-type PLD repair was measured by the decrease in survival of V79 Chinese hamster cells by postirradiation treatment with 3ABA. The slow-type PLD repair was measured by the increase in survival by posttreatment with conditioned medium (CM), which became conditioned by growing a crowed culture of cells and supports the slow-type PLD repair. RESULTS: Up to 1 mM, 3-ABA inhibited the slow type repair; at doses of 2 mM and above, it inhibited the fast type of PLD repair. CONCLUSION: There are quantitative differences in cellular effects of 3ABA dependent on concentration. Poly (ADP-ribose) appears to play an important role in the PLD repairs and has little effect on the repair of sublethal damages.

Animals↗

Highly polarized expression of carbohydrate-binding protein p33/41 (annexin IV) on the apical plasma membrane of epithelial cells in renal proximal tubules.

p33/41 is a Ca(2+)-dependent carbohydrate-binding protein and is identical to annexin IV, a member of the annexin protein family. The localization of p33/41 in bovine kidney specimens was investigated immunohistochemically by use of specific polyclonal antibodies. The most interesting finding on immunostaining was that p33/41 was highly concentrated in the apical plasma membrane of the epithelial cells in the proximal tubules contrary to the distribution throughout the cytoplasm in the papillary ducts and papilla epithelium. The enrichment of p33/41 in the apical membrane was confirmed by immunoblotting of the brush border membrane fraction prepared from a kidney homogenate. Sequential extraction with EDTA and Triton X-100, and a partition experiment with Triton X-114 revealed that most p33/41 associates with the renal brush border membrane in a Ca(2+)-independent manner and is integrated into the membrane like intrinsic membrane proteins.

Animals↗

A comparative ESR study of some paramagnetic materials as probes for the noninvasive measurement of dissolved oxygen in biological systems.

The ESR properties of three types of paramagnetic material, active charcoal, fusinite and a stable nitroxide radical 4-oxo-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPONE), were examined in order to evaluate their suitability as probes to measure dissolved intra- and extra-cellular oxygen. Although, with changes in oxygen concentration, a greater change in the linewidth of ESR signals was observed with fusinite or active charcoal, it took a long time (15 min for active charcoal and more than 6 h for fusinite) for equilibrium to be achieved. On the other hand, equilibrium was reached very rapidly in the case of the TEMPONE spectra although the sensitivity to changes in oxygen concentration was only moderate. Furthermore, since lipid bilayers are permeable to TEMPONE, this compound can be used to measure intracellular oxygen concentration when employed in combination with membrane-impermeable spin-broadening reagents which act on ESR signals arising from extracellular probes. A perdeuterated derivative of TEMPONE is useful in that it gives a greater signal-to-noise ratio and greater sensitivity to changes in oxygen concentration. In conclusion, active charcoal is suitable as a probe for extracellular oxygen in a system where changes are slow, while nitroxide is a versatile probe for measuring rapidly changing intra- and extra-cellular oxygen concentrations.

Charcoal↗

[Difference of thallium-201 kinetics between VX-2 tumors and inflammatory lesions in rabbits].

To evaluate the difference of thallium-201 chloride (201Tl) kinetics between malignant tumors and inflammatory lesions, 201Tl scintigraphy was performed in the 30 rabbits with variable sized VX-2 tumors; and in the 27 rabbits with variable sized inflammatory lesions induced by turpentine oil and the solution of auto-feces. The degree of 201Tl uptake was expressed as the count ratios of the lesions over the contralateral normal muscle tissue, and the early uptake ratio (1 min after the injection) and the delayed uptake ratio (30 min) were acquired. The retention index derived from these ratios was used to assess the degree of 201Tl washout from the lesions. When dividing both the tumors and inflammatory lesions into the large lesions (more than 40 mm in diameter) and smaller ones, different 201Tl kinetics according to the size of the lesions were demonstrated. In the small lesions, the VX-2 tumors showed higher early and delayed uptake ratios and a faster washout than the inflammatory lesions. In contrast, in the large lesions, both the early and delayed uptake ratios were not significantly different; however, the retention index in the tumors was higher compared to the inflammatory lesions. Thus, our animal study indicates that 201Tl kinetics are different according to the size of the tumor and inflammatory lesions, and that in the small lesions the higher tumor uptake compared to the inflammatory lesions may be available to differentiate. However, in the large sized lesions, assessment of the 201Tl washout from the lesions is necessary for differentiation.

Animals↗

Antioxidant activity of nitroxide radicals in lipid peroxidation of rat liver microsomes.

Inhibition of lipid peroxidation by nitroxide radicals in rat liver microsomes was studied using several nitroxide compounds which have various lipophilicities. Addition of NADPH to microsomes in an oxygen atmosphere induced lipid peroxidation as indicated by the increase of thiobarbituric acid (TBA)-reactive substances, hydroperoxide, conjugated diene, and oxygen consumption. Lipid peroxidation was inhibited by nitroxides located in both water phase and membrane. Oxygen consumption and the generation of active oxygens were inhibited by water-soluble nitroxides but not by intramembranous ones. Intramembranous nitroxides significantly prevented the production of conjugated dienes and lipid hydroperoxides. The facts suggest that water-soluble nitroxides interfere with the generation of active oxygens as preventive antioxidants, while intramembranous nitroxides inhibit the formation of lipid alkyl radical as chain-breaking antioxidants. The intensity of ESR signals due to intramembranous nitroxide radicals remained constant during the inhibition reaction of lipid peroxidation, suggesting that the prevention of lipid peroxidation is coupled with the reversible redox reaction between nitroxides and the reduced nitroxides in microsomes. The reduced forms of nitroxides, which were prepared by the reduction of intramembranous nitroxides, also inhibited the generation of TBA-reactive substances as well as the parent nitroxide. These facts indicate that either intramembranous nitroxide radicals or their reduced forms, "hydroxylamines," may be useful lipophilic antioxidants.

Animals↗

Aging retards spin clearance from mouse brain and food restriction prevents its age-dependent retardation.

After the nitroxyl radical 3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl (carbamoylPROXYL) was intraperitoneally administered to mice, the time courses of changes in the intensity of signals in L-band electron spin resonance spectra from their brains were measured. The spin clearance rate of old, ad libitum-fed mice was lower than that of young, ad libitum-fed mice. The rate of old, food-restricted mice was significantly higher than that of old, ad libitum-fed mice and was comparable to that of young, ad libitum-fed mice. The spin clearance was found to be due to the one-electron reduction of the nitroxyl radical, because a decreased spin intensity of it in serum was restored to the original level by potassium hexacyanoferrate (III) oxidation in vitro. These results suggest that reducing capacity in the cardiovascular system of mice is decreased with advancing age, and that food restriction prevents an age-dependent decrease in the reducing capacity.

Aging↗

Hyperthermic enhancement of cytotoxicity and increased uptake of cis-diamminedichloroplatinum(II) in cultured human esophageal cancer cells.

Thermal enhancement of cytotoxicity of cis-diamminedichloroplatinum(II) (CDDP) has been well recognized and applied clinically to chemotherapy of various malignancies, but its fundamental mechanism remains to be elucidated. In order to obtain a clue to this mechanism, we analyzed the effect of hyperthermia on the uptake and subsequent distribution of [195mPt]CDDP in two lines of esophageal cancer cells (KYSE-150 and KYSE-170) established from clinical patients. First, we observed a significant increase in [195mPt]CDDP uptake by both types of cells at increasingly higher temperatures. The incorporated CDDP was distributed between the nucleus and the cytosol at a ratio of approximately 3:1, and the ratio remained the same at various temperatures. The CDDP was found in all four molecular fractions, i.e., DNA, RNA, protein, and TCA-soluble, with a slight preference for DNA at higher temperatures. Enhancement of cytotoxicity required simultaneous, and not sequential, treatments with CDDP and hyperthermia; hyperthermia after CDDP treatment increased the efflux of CDDP from the cells, and rather reduced the cytotoxicity of CDDP. These results suggest that thermal enhancement of the cytotoxicity of CDDP is caused mainly by acceleration of the drug entry into the cell, probably due to increased permeability, and a consequent increase in the amount of CDDP binding to DNA. This mechanism gives support for clinical trial of simultaneous treatment with CDDP and hyperthermia.

Carcinoma, Squamous Cell↗

In vivo EPR measurement of radical reaction in whole mice--influence of inspired oxygen and ischemia-reperfusion injury on nitroxide reduction.

In vivo EPR measurements were carried out with whole mice to evaluate the influence of inspired oxygen and ischemia-reperfusion injury on spin-clearance of the nitroxide radicals which were administered intravenously or intramuscularly. Nitroxide radicals in head, abdomen, or muscle domains were composed of sharp triplet lines. The peak heights decreased gradually with time. The reduction of nitroxide radicals depended both on the inspired oxygen concentration and on the domains. Femoral ischemia-reperfusion injury also affected spin-clearance of the nitroxide radical in the thigh. The results were discussed with regard to the generation of active oxygen species.

Animals↗

Whole mouse measurement of paramagnetism-loss of nitroxide free radical in lung with a L-band ESR spectrometer.

Paramagnetism-loss of nitroxide radical in lung of whole mouse was characterized using L-band ESR technique. The nitroxide, hydroxy-TEMPO, which had been injected trans-tracheally into mouse lung was confirmed to lose its paramagnetism in one electron reduction. The reduction activity remained even after lavage of lung. The reduction was inhibited by N-ethylmaleimide, a membrane-permeable sulfhydryl-blocker, though direct reduction of the radical by sulfhydryls was not observed in vitro. Sulfhydryl-blockers floating in membranes also inhibited the reduction, depending on their chain length. The results indicate that the reduction may be done within plasma membranes of alveolar epithelial cells.

Animals↗

[Usefulness of 201TlCl SPECT for evaluation of treatment effect of pancreatic cancer].

To assess the treatment effect of pancreatic cancer, thallium 201 chloride (201TlCl) SPECT was performed in three patients. All of the patients before and after treatment showed the same change between the tumor/liver uptake ratio of 201TlCl and the serum level of CA 19-9. In one of the patients, tumor shrinkage was not observed on CT. However, the uptake ratio decreased, accompanying with a reduced serum level of CA 19-9. These results indicate that 201TlCl SPECT is useful to evaluate therapeutic effect of pancreatic cancer.

Adult↗

Demonstration of inguinal hernia by means of peritoneal 99mTc-MAA scintigraphy with a load produced by standing in a patient treated by continuous ambulatory peritoneal dialysis.

A 45-year-old man receiving continuous ambulatory peritoneal dialysis developed scrotal swelling and edema which was aggravated in the standing position. Physical examination failed to find inguinal hernia and although ultrasonography revealed the patent had processus vaginalias, it failed to prove its continuity to the peritesticular space of the tunica vaginalis. Peritoneal scintigraphy with intraperitoneal instillation of 99mTc-Macroaggregated albumin followed by standing clearly demonstrated the connection. The use of the standing load makes possible faster visualization of a positive finding and more accurate diagnosis than examination in the supine position.

Hernia, Inguinal↗

Intrinsic radiosensitivity and PLD repair in osteosarcoma cell lines.

The response to radiation of seven osteosarcoma cell lines was analysed by in vitro colony-forming assay and compared with that of eight human fibroblast strains. The values of D0, the surviving fraction after 2 Gy (S2Gy), and the mean inactivation dose (D) of osteosarcoma cells in log-phase culture were significantly higher than those of fibroblast strains (p less than 0.01). PLD (potentially lethal damage) repair of osteosarcoma cells evaluated in the plateau phase of growth showed great variation for enhancement of survival, although all of the values were maximized within 12 h after irradiation. In the osteosarcoma, intrinsic radiosensitivity in vitro reflected the clinical response to radiation. However, the capacity for PLD repair might not be a good indicator for predicting the results of radiation therapy.

Cell Survival↗

Bone and gallium scintigraphy in sacral chordoma. Report of four cases.

Bone scintigraphy with Tc-99m HMDP and gallium scintigraphy were evaluated in four patients with a primary sacrococcygeal chordoma. All lesions showed a photon-deficient or cold lesion corresponding to the tumor on bone scintigraphy, with no abnormal accumulation clearly observed on gallium scintigraphy. These findings led the authors to conclude that a midline sacrococcygeal tumor showing reduced uptake or a cold lesion on bone scintigraphy and no increased accumulation on gallium scintigraphy could be a chordoma rather than the malignant neoplasm suspected in this region.

Adult↗

Clinical and experimental studies on the mechanism of abnormal accumulation in lung scanning with 123I-IMP.

To investigate the intrapulmonary kinetics of N-isopropyl-p-I-123-iodoamphetamine (123I-IMP), lung scanning with 123I-IMP was performed in patients with various lung disorders. Compared with the normal lung field, abnormal accumulation of 123I-IMP was detected in all patients in delayed imaging performed 24 h after 123I-IMP injection. These sites were within areas of absent or reduced perfusion observed by pulmonary perfusion scanning using 99Tcm-macroaggregated albumin (99Tcm-MAA). A similar phenomenon was seen in additional experiments in rabbits with regional pulmonary arterial hypoperfusion resulting from a balloon catheter-induced bronchial occlusion. 123I-IMP accumulation in areas where 99Tcm-MAA images are absent or decreased may be explained by the ability of 123I-IMP to penetrate significantly narrowed microvascular beds with reduced perfusion. Our clinical and experimental results indicate that pulmonary arterial perfusion, particularly hypoperfusion, influence the pulmonary kinetics of 123I-IMP. This compound is a potentially useful non-particulate agent for the assessment of pulmonary arterial perfusion.

Aged↗