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H Maezawa

Publications and source records attributed to H Maezawa.

154 records · Page 9Linked to original sources

A low molecular weight binding protein for organic anions (Z protein) from human hepatic cytosol: purification and quantitation.

Human Z protein from liver was purified to homogeneity. The protein has a molecular weight of 11,000 an an isoelectric point of pH 5.8. Circular dichroism spectra of Z protein-bilirubin (unconjugated and diglucuronide) complexes revealed two ellipticity extrema, a negative peak at 460 nm, and a positive peak at 410 nm. Human serum albumin had a higher affinity for bilirubin than did Z protein. Fluorescence studies showed the approximate association constants of this protein and bilirubin, bromosulfophthalein, and indocyanine green were 10(6) M-1, 10(5) M-1, and 10(6) M-1, respectively. Immunofluorescence studies revealed that Z protein was localized in the cytoplasm of hepatocytes, proximal tubular epithelium, and epithelial cells of the small intestine. Radioimmunoassay studies were done to assess the amount of Z protein in controls and in various liver diseases. The highest concentrations of Z protein were found in the liver, kidney, heart muscle, and small intestine, in that order. In cases of acute and chronic hepatitis, hepatic Z protein concentrations were generally decreased, whereas serum Z protein concentrations were increased. In contrast, both serum and hepatic Z protein concentrations were decreased in cases of constitutional hyperbilirubinemia.

Bilirubin↗

Permeability of intracranial extracerebral vessels in stroke-prone SHR.

Permeability of intracranial extracerebral arteries of stroke-prone spontaneously hypertensive rats (SHRSP) was studied using labeling techniques (ferritin and horseradish peroxidase), at the cellular level. In the arterial endothelial cells, the tracer molecules were slowly but constantly transported by the plasmalemmal vesicles to the subendothelial space. This endothelial transportation of the tracers into these cerebral arteries did not seem to be significantly influenced by aging, increased blood pressure, hyperlipidemia or the existence of cerebral bleeding and infarction. Around the adventitia, there were a great number of periadventitial capillaries, especially near bifurcations. In the periadventitial capillaries, the tracer molecules were readily trapped by endothelial cells and were quickly transported to pericapillary spaces. The tracer molecules were then detected in the phagocytes adjacent to the deeper layers of the media, and further in the medial smooth muscle cells. The possibility that large amounts of plasma components are supplied to the media from periadventitial capillaries in the intracranial extracerebral arteries has to be considered in the pathogenic mechanisms of cerebrovascular lesions.

Animals↗

Increased transendothelial channel transport of cerebral capillary endothelium in stroke-prone SHR.

Permeability of brain capillaries of stroke-prone spontaneously hypertensive rats (SHRSP) was studied using labelling (horseradish peroxidase) and cytochemical techniques at the cellular level. In the cerebral capillary endothelium the tracer molecules were quickly transported by abundant transendothelial channels which directly connected the capillary lumen to the subendothelial space. Transendothelial channels are abundant and should be postulated as structural formations engaged in the increased transport of proteins across the capillary endothelium. Ultracytochemical studies revealed that the channels, bounded by indistinct delimiting membranes, initially had no acid phosphatase activity. With the passage of time, however, the channels showed acid phosphatase activity and were lined with distinct membranes. These observations suggested that the lysosomes might fuse with the transendothelial channels and might play an important part in the transport of macromolecules.

Acid Phosphatase↗

Ultrastructural characteristics of occluded perforating arteries in stroke-prone spontaneously hypertensive rats.

We studied ultrastructurally cerebral perforating arteries in 60 stroke-prone spontaneously hypertensive rats (SHRSP), which were sequentially killed at 4-52 weeks of age before showing symptoms of stroke. Another 24 SHRSP were killed soon after they showed symptoms of cerebral infarction. The initial vascular lesions observed in the asymptomatic group included focal cytoplasmic necrosis in the outer layers of the media. This change progressed to widespread medial necrosis with time. In the infarction group, numerous monocytes were seen adhering to the endothelium of the arteries having advanced medial damage. Following the adherence of monocytes to the endothelium, large amounts of plasma components were visible in the arterial wall. The accumulation of the plasma components (especially fibrin) thickened the wall, narrowed the lumen, and resulted in occlusion. These results suggest that monocytes may affect the endothelium, perhaps disturbing the so-called blood-brain barrier to proteins. The monocytes may therefore be closely related to the occurrence of arterial occlusion with resultant cerebral infarction.

Animals↗

Comparative study of thermoradiosensitization by misonidazole and metronidazole in vivo: antitumour effect and pharmacokinetics.

Tumour control by local hyperthermia (43.5 degrees C, 30 min) and radiation (20 Gy) given in combination with misonidazole (MISO) or metronidazole (METRO) was studied using FSa-II murine fibrosarcoma. When MISO or METRO (5 mmol/kg) was given 30 min before heat and subsequently treated with radiation, tumour regression was observed for both agents. Radiation dose-response curves for MISO and METRO with heating at 43.5 degrees C for 30 min were identical. Mouse foot reaction was used to evaluate local toxicity following combined heat, a nitroimidazole and radiation treatment. MISO enhanced the magnitude of foot reaction and prolonged the recovery time compared with heat plus radiation controls. There were no observable differences of foot reaction between animals treated with heat plus radiation and those animals treated with heat, radiation and METRO. Pharmacokinetics of the nitroimidazoles heated at 43.5 degrees C for 30 min in FSa-II tumours were investigated as a possible mechanism of thermal sensitization. Local hyperthermia did not alter the pharmacokinetics of METRO. Tumour concentration and tumour/plasma ratio of MISO were slightly decreased during heating. Since the hypoxic metabolism of the nitroimidazoles did not increase significantly during the heat treatment, the thermal enhancement of MISO or METRO radiosensitization cannot be explained by the increase in hypoxic cytotoxicity of the nitroimidazoles at elevated temperature alone. The two nitroimidazoles also were not accumulated in the tumour after heating. Therefore, alternation of pharmacokinetics is not the major mechanism for the thermal enhancement of nitroimidazole radiosensitization. The METRO radiosensitization effect became identical to that of MISO at elevated temperatures is of particular importance in clinical radiosensitization. The very low local and systemic toxicity together with the high efficacy of METRO at elevated temperatures will make it an attractive candidate as a future clinical radiosensitizer.

Animals↗

Time course of development of metastasis in irradiated Lewis lung carcinoma: relationship between primary tumor volume and metastasis.

The influence of local irradiation on the development of metastases and primary tumor volume was studied in Lewis lung carcinoma growing intramuscularly in the hind leg of C57BL/6 mice. The time course of development of metastases was determined from the size of the lung colonies at autopsy by determining the growth rate of the colonies. Irradiation within five days after tumor cell injection inhibited the incidence of metastases in accordance with irradiation dose. For irradiation more than seven days after the injection, promotion of metastases was observed around the time of the experiment as a function of irradiation dose and tumor volume. After the irradiation phase, the development of metastases was inhibited in accordance with radiation dose. When delay in metastasis was defined as additional days needed to develop two or ten colonies compared with controls, the relationship between delay and dose was linear. At the regrowth phase of the primary tumor, the incidence of metastases from the irradiated tumor was reduced in comparison with that from unirradiated tumors of the same size. Inhibition of metastases was observed only at 5 Gy and showed slight dose-dependency. Mechanisms in the development of metastases as they related to these findings are also discussed.

Animals↗

Survival of mice and hematopoietic stem cells in bone marrow after intermittent total body irradiation.

As a preparative procedure for bone marrow transplantation, intermittent total body irradiation (TBI) has been used in our hospital. The biological significance of this method, in which the instantaneous dose rate is high but the average dose rate is low, has not been evaluated to date. The hematopoietic responses caused by both intermittent and continuous TBI were compared. In the intermittent irradiation, mice in a moving irradiation chamber were exposed under a small field (2 X 35 cm2), and the instantaneous and average dose rates were 1 Gy/min and 0.25-0.12 Gy/min, respectively. The average dose rate was adjusted to the same level in both irradiation methods. LD50/30 and survival of colony-forming units (CFU) in culture and survival of endogenous CFU in the spleen from female BDF1 mice were the same with the two methods. These results show that the response of hematopoietic stem cells depends on the average dose rate, not on the instantaneous dose rate. Our findings suggest that intermittent irradiation, as well as the continuous method, would be useful for preparing patients before bone marrow transplantation.

Animals↗