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Biomedical subjects

R Kimura

Publications and source records attributed to R Kimura.

At least 19 recordsLinked to original sources
PubMed1992

Proliferating cell nuclear antigen (PCNA) immunostaining as an alternative to bromodeoxyuridine (BrdU) immunostaining for brain tumours in paraffin embedded sections.

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and BrdU using anti-PCNA and anti-BrdU monoclonal antibodies, respectively, was performed in 16 human brain tumours, including 3 glioblastomas multiforme, 2 anaplastic astrocytomas, 1 cerebellar astrocytoma, 2 recurrent meningiomas, 4 non-recurrent meningiomas, 3 neurinomas and 1 medulloblastoma. Patients with brain tumours received an injection of bromodeoxyuridine (BrdU) intravenously during surgery, and tumour specimens were fixed in 70% ethanol and embedded in paraffin. The percentage of positive cells for PCNA was compared with a BrdU labelling index using adjacent paraffin-embedded sections. The percentage of PCNA-positive cells was correlated with the BrdU labelling index and the histological malignancy of the brain tumours. The correlation coefficient was 0.84. This suggests that the immunohistochemical staining for PCNA in paraffin sections is a good alternative to the BrdU labelling index.

Antigens, Neoplasm↗
PubMed1992

Immunological tolerance to hapten prevents subsequent induction of hapten-immune pulmonary interstitial fibrosis (HIPIF).

Pulmonary interstitial fibrosis (PIF) is a morphological term which in part can be defined as accumulation of collagen in the extracellular matrix. Previously we showed that hamsters sensitized with 2,4,6-trinitro-1-chlorobenzene (TNCB) developed PIF 14 days after an intratracheal challenge with 2,4,6-trinitrobenzene sulfonic acid (TNBS). The participation of delayed-type hypersensitivity (DTH) in lung collagen deposition was clearly demonstrated. In this paper, we use an adaptation of this model to mice and show that the lung collagen deposition observed was related to the genetic ability of the strain to maintain a DTH response to the immunizing hapten (TNP). Specifically, the lung collagen deposition on Day 14 in hapten-sensitized, challenged animals in high responder to TNP (BALB/c, H-2d) was higher than that in low responder mouse (C57BL/6, H-2b). Furthermore, aged C57BL/6 strain (retired breeders) possessed a DTH response to TNP and produced significantly higher accumulation of hydroxyproline than that of TNBS-challenged-only animals. A DTH mechanism for the induction of the fibrosis is consistent with the observation that responder mice that were made tolerant to the antigen were unable to respond to the lung challenge with a specific increase in lung index or collagen deposition. These results suggest that effector T lymphocytes that are important in DTH play a key role in the regulation of lung collagen deposition in hapten-immune pulmonary interstitial fibrosis (HIPIF) in mice.

Age Factors↗
PubMed1992

Binding characteristics of naftopidil and alpha 1-adrenoceptor antagonists to prostatic alpha-adrenoceptors in benign prostatic hypertrophy.

Binding properties of naftopidil and alpha 1-adrenoceptor antagonists to alpha-adrenoceptors in prostates from benign prostatic hypertrophy (BPH) were characterized by radioreceptor assays using [3H]prazosin and [3H]rauwolscine. Specific binding of [3H]prazosin and [3H]rauwolscine in human prostatic membranes was saturable and of high affinity, and it showed a pharmacological specificity which characterized alpha 1 and alpha 2-adrenoceptors, respectively. Naftopidil and several alpha 1 antagonists competed for prostatic [3H]prazosin binding in order: R-(-)-YM-12617 greater than prazosin greater than bunazosin greater than terazosin greater than naftopidil greater than urapidil, and the inhibitory effect (Ki = 11.6 nM) of naftopidil was 10 to 45 times less potent than quinazoline derivatives such as prazosin, bunazosin and terazosin. The potencies of these antagonists in competing for [3H]prazosin binding sites in human prostates correlated well with their pharmacological potencies (pA2). Scatchard analysis indicated that the decrease of prostatic [3H]prazosin binding by naftopidil was due to a marked increase in the Kd value without a change in the Bmax value. The inhibition of prostatic [3H]prazosin binding by naftopidil was reversible. Naftopidil also inhibited prostatic [3H]rauwolscine binding (Ki = 70.0 nM). Thus, it is suggested that naftopidil antagonizes alpha 1-adrenoceptors in human prostates in a competitive and reversible manner.

Adrenergic alpha-Antagonists↗
PubMed1992

Nasal absorption of digoxin in rats.

The nasal administration of digoxin was studied in rats and compared to intravenous, intraduodenal and rectal administration of the drug. The results indicated that the plasma level of digoxin after nasal administration was comparable to the level after intravenous injection. Administration by the intraduodenal and rectal routes resulted in considerably lower plasma levels. These data reveal that digoxin absorption across the nasal membranes is a reasonable approach. In the in situ nasal and intestinal perfusion experiments, digoxin disappeared from the perfusate following the apparent first-order kinetics. The nasal and intestinal absorption rate of digoxin was reduced by an increase in the perfusion volume. The plot of absorption rate constant against 1/volume resulted in a straight line, suggesting that digoxin is absorbed from nasal mucosa by a passive diffusion process.

Absorption↗
PubMed1992

[Subcellular distribution of porphyrins and anti-lipid peroxidative effect in protoporphyrin-administered rat liver].

The distribution and the anti-lipid peroxidative effects of porphyrins in the hepatic subcellular fractions in rats were studied after intravenous administration of protoporphyrin (PP). PP and/or PP-derived porphyrins were mainly distributed in the membrane-containing fractions of 600 x g-, 10,000 x g- and 100,000 x g-sediment from the liver homogenates of rats receiving a 20 mg/kg dose of PP. The lipid peroxidation induced by L-ascorbic acid in the fractions of 600 x g-, 10,000 x g- and 100,000 x g-sediment from the PP-treated rats was suppressed during 1-168 h, 1-168 h and 12-168 h, respectively, after the PP treatment. The suppression of the peroxidation in the liver mitochondria from the PP-treated rats was further enhanced by the addition of the hepatic cytosol from the PP-treated rats. The extent of the suppression by the addition of the cytosol from the PP-treated rats at 24 h after the PP administration was greater than those at 0 and 168 h after the PP administration. These results indicate that PP and/or PP-derived porphyrins distributed in the liver still exert antioxidative actions and that there might exist some unknown factors enhancing the actions in the hepatic cytosol.

Animals↗
PubMed1992

Analysis of tumor necrosis factor and lymphotoxin secreted by incubation of lymphokine-activated killer cells with tumor cells.

This study investigated the secretion of a tumor necrosis factor (TNF) and lymphotoxin (LT) from lymphokine-activated killer (LAK) cells during co-culture with glioblastoma cell lines, autologous glioma cells, and other non-gliomatous tumor cell lines (K562 and Daudi). Cytokine secretion from peripheral blood mononuclear cells (PBMC) was also examined. The TNF activity of culture supernatants was measured by L cell cytotoxic assay, and a neutralization test using anti-TNF and/or anti-LT antibodies determined whether the cytotoxic activity was due to TNF or LT. The results show that LAK cells secrete both TNF and LT during monoculture and release increased amounts of TNF and LT with non-gliomatous tumor cell stimulation, but PBMC secrete only TNF with tumor cell stimulation. Glioblastoma or anaplastic astrocytoma cells, however, did not stimulate cytokine secretion from either LAK cells or PBMC. This indicates a discrepancy between the capability of LAK cells to lyse malignant glioma cells and cytokine secretion from LAK cells, and suggests that malignant glioma cells may produce some factors which inhibit cytokine secretion from LAK cells.

Astrocytoma↗
PubMed1992

A sustained occupancy in vivo of cardiovascular calcium antagonist receptors by mepirodipine and its relation to pharmacodynamic effect in spontaneously hypertensive rats.

The occupancy in vivo of cardiovascular and cortical Ca++ antagonist receptors by mepirodipine in spontaneously hypertensive rats (SHR) was investigated. At 0.5, 3 and 6 hr after an oral administration of mepirodipine (3 mg/kg) in SHR, there was a significant (69, 51 and 41%, respectively) decrease in the number of cardiac (+)-[3H]PN 200-110 binding sites (Bmax) compared to control values. At 12 hr later, the Bmax value returned to the control value. On the other hand, the mepirodipine administration had little effect on the dissociation constant (Kd) for cardiac (+)-[3H]PN 200-110 binding except at 0.5 hr, when there was a significant increase in the value, suggesting a change in the density rather than affinity of Ca++ antagonist receptors. In the cerebral cortex of these rats, there was a significant (34%) decrease in Bmax values for (+)-[3H]PN 200-110 binding only at 0.5 hr after mepirodipine administration. In contrast, nifedipine administration had a significant increase in Kd values for cardiac (+)-[3H]PN 200-110 binding without a change in Bmax values. The occupancy of cardiac Ca++ antagonist receptors by mepirodipine correlated significantly with its hypotensive effect in SHR. There was approximately a 39 mm Hg reduction of blood pressure by occupying 50% of these receptors. After an i.v. injection of (+)-[3H]PN 200-110 (15 microCi) to SHR, there was specific binding of the ligand in particulate fractions of heart, aorta, ileum and cerebral cortex, but not liver and kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Fundamental study on hyperthermic chemotherapy using adriamycin-loaded hydroxyapatite].

We developed a porous hydroxyapatite ceramic (HAP) incorporating adriamycin (ADM), that is, ADM-HAP as a new delivery system (DDS) to release ADM gradually. We also researched the possibility of hyperthermic chemotherapy using ADM-HAP by in vitro and in vivo experiments. As for in vitro experiments, we implanted HAPs into uniform Agar-Phantom, and observed thermal distribution generated by Thermotron-RF 8 using thermography. Then we found the hot spot that the edge temperature of HAPs always at the range of 0.5-0.7 degrees C than in the other regions. On the other hand, slow constant release (1%) of ADM from ADM-HAP in PBS was recognized for 24 hrs up to 30 days. When the incubating temperature was shifted up to 42.5 degrees C or 44 degrees C from 37 degrees C, the quantity released over 24 hrs increased about 1.1-fold or 1.3-1.4-fold of the cases at 37 degrees C, respectively. In the in vivo experiment, we inoculated Sarcoma 180 cells in the leg of ddY-mice, and measured the tumor growing times by the treatment of hyperthermia+ADM (whole body), hyperthermia+ADM (tumor region) or hyperthermia+ADM-HAP (tumor region). Then we found that the effect of hyperthermia with ADM-HAP inhibited synergistically the tumor growth as compared with hyperthermia with ADM. Consequently, we succeeded in tumor growth inhibition by increasing the temperature and by limiting ADM release to only a target region using hyperthermia with ADM-HAP.

Animals↗
PubMed1992

Protoporphyrin overload in unrestrained rats: biochemical and histopathologic characterization of a new model of protoporphyric hepatopathy.

We determined the feasibility of producing protoporphyric hepatopathy in unrestrained rats by infusing protoporphyrin into their portal circulation via chronic indwelling catheters. Sprague-Dawley rats, 200-300 g, received single (8.5-27.8 mumol) or multiple (64.1-208.7 mumol) infusions of protoporphyrin over 3-240 h. Single protoporphyrin infusions increased the hepatic protoporphyrin concentration from < 1 nmol/g up to 1368 nmol/g; multiple infusions up to 3908 nmol/g. The maximal non-hepatic tissue concentrations averaged 243 nmol/g in the spleen. Hepatocanalicular and ductular birefringent pigmented deposits were found in all livers, generally proportional to the protoporphyrin load. Aggregates of crystalline protoporphyrin were detected in biliary ductules, canaliculi, hepatocytes, Kupffer cells and fat-storage cells by electron microscopy. Laboratory abnormalities included elevations of the transaminases, LDH, GGTP and bilirubin and a modest fall in the haematocrit suggesting a mixture of red blood cell and hepatic injury. Thus, protoporphyric hepatopathy was produced by infusions of protoporphyrin into the portal circulation. This model may aid in understanding the pathogenesis and pathophysiology of liver disease in protoporphyria.

Animals↗
PubMed1992

Delayed-type hypersensitivity responses regulate collagen deposition in the lung.

A previous report showed that hamsters immunized by epicutaneous application of 2,4,6-trinitrochloro-1-benzene (TNCB) were susceptible to the development of pulmonary interstitial fibrosis (PIF) if challenged in the lung with the water-soluble form of this hapten 2,4,6-trinitrobenzene sulphonic acid (TNBS). In this study, we investigated the immunological mechanisms that contributed to increased collagen content in the lungs of hapten-immune hamsters after receiving a pulmonary challenge of the sensitizing hapten trinitrophenol (TNP). In order to evaluate the concept that delayed-type hypersensitivity (DTH) reaction modulated their response to TNP in the lung such that it eventuated into PIF, we compared the cutaneous DTH response (48 hr after challenge) with lung collagen deposition (14 days after challenge) in several lines (strains) of hamsters. The inbred LSH strain, was a high responder in the DTH assay to TNP and developed non-resolving PIF in the hapten-immune animals. This is called hapten-immune pulmonary interstitial fibrosis or HIPIF. We also observed that female LSH hamsters were more susceptible to HIPIF induced by TNP than males. On the other hand, age factors influenced DTH and PIF in random-bred LVG hamsters since young hamsters (3 months old) were low responders to TNP and did not develop PIF in the HIPIF model but matured LVG hamsters (retired breeders) possessed DTH reactivity to TNP and subsequently developed PIF. These results suggest that lung collagen deposition in hapten-immune hamster is regulated by T-lymphocyte-mediated immune inflammation (DTH) in the lung and both are dependent on the ability to develop a cutaneous DTH reaction to the hapten. The elucidation of possible mechanisms of DTH-mediated non-granulomatous, non-resolving PIF is important for understanding of the role of environmental chemicals similar in action to haptens in the mediation of skin and lung diseases.

Aging↗
PubMed1991

[3H]bunazosin, a novel selective radioligand of alpha 1 adrenoceptors in human prostates.

The binding properties of a new radioligand, [3H]bunazosin, were studied in membranes of human prostates with benign prostatic hypertrophy (BPH). Specific binding of [3H]bunazosin was saturable, reversible, and of high affinity (Kd = 0.55 +/- 0.04 nM). The density of [3H]bunazosin binding sites (Bmax) was 676 +/- 33 fmol/mg. protein. [3H]Bunazosin rapidly associated with its binding sites in membranes of human prostates and reached steady state by 20 min. at 25C. The rate constants for association and dissociation of [3H]bunazosin binding were calculated to be 0.11 +/- 0.01/nM/min. and 0.05 +/- 0.02/min. (n = 4), respectively. Seven alpha 1 adrenoceptor antagonists competed with [3H]bunazosin for the binding sites in the rank order: R-(-)-YM-12617 greater than prazosin greater than SGB-1534 greater than bunazosin greater than terazosin greater than naftopidil greater than urapidil. In parallel studies with [3H]bunazosin, the Kd and Bmax values for [3H]prazosin binding in human prostates were slightly lower. There was a similarity in the potency and rank order of seven alpha 1, adrenoceptor antagonists for the inhibition of [3H] bunazosin and [3H]prazosin binding in human prostates. The new [3H]bunazosin binding assay in human prostates is remarkable for its low degree of nonspecific binding as compared to [3H]prazosin, especially at high ligand concentrations. Thus, [3H]bunazosin may become a useful radioligand for the further analysis of the alph 1 adrenoceptor binding sites in human prostates.

Adrenergic alpha-Antagonists↗
PubMed1991

Mechanisms of absorption of inorganic mercury from rat small intestine. IV: Effect of chelating agents and cysteine on absorption of mercuric chloride in situ and in vitro.

The effects of chelating agents (citric acid, tartaric acid, penicillamine and ethylenediaminetetraacetic acid) and cysteine on the absorption of HgCl2 were investigated in rats. Perfusion of the small intestine showed that the chelating agents and cysteine decreased the absorption of HgCl2 depending on their stability of constants with Hg2+, under the predominant conditions of water absorption and secretion. The difference in absorption of HgCl2 between both conditions was inversely correlated with their logarithmic stability constant values. These agents decreased the transport of HgCl2 through the everted intestinal wall and the uptake of HgCl2 by the intestinal brush border membrane in a similar manner. From these results, it is suggested that the chelating agents and cysteine decrease the absorption of HgCl2 through the pores of the brush border membrane due to the solvent drag effect.

Animals↗
PubMed1991

Antioxidative effect of protoporphyrin on lipid peroxidation in tissue homogenates of intravenously administered rats.

Effect of intravenous administration of protoporphyrin IX (PP) on lipid peroxidation was studied in rats. PP and/or PP-derived porphyrins were found to be mainly distributed in livers, spleen and lungs. Dose-dependent decreases in the Fe2+ and L-ascorbic acid-stimulated lipid peroxidation in homogenates of livers and dose-dependent increases in porphyrin concentration in livers were observed after the PP injection. In the experiments with a 20 mg/kg dose of PP, the peroxidation level in the liver homogenates reached its minimum level during the period of 3 to 24 h accompanying the high porphyrin concentration in livers after the administration. After 96 h, a relatively high porphyrin concentration was still retained, but decreases in the peroxidation levels had ceased. PP administration caused a dose-dependent decrease in the endogenous lipid peroxides in livers within 0.5 h and the low levels were maintained throughout the course of the 168-h study. These results clearly show that the administered PP is distributed in the liver and inhibits the lipid peroxidation in vivo.

Animals↗
PubMed1991

Giant middle cerebral artery aneurysm with parent artery occlusion--case report.

A 54-year-old female was admitted with consciousness disturbance and right hemiparesis. Computed tomographic (CT) scans and angiograms revealed diffuse subarachnoid hemorrhage, a partially thrombosed, giant middle cerebral artery aneurysm (5 x 5 x 4 cm), and occlusion of the parent artery at the aneurysm site. Despite conservative treatment, a generalized convulsion occurred. Emergency CT scans revealed irregular enlargement of the left temporal high-density mass and severe mass effect due to cerebral infarction. Barbiturate coma therapy was administered, but she did not recover and died 9 days after admission. Only two cases of ruptured aneurysm with simultaneous occlusion of the major cerebral vessels have been reported, both with poor outcome. In this case, the mechanism of parent artery occlusion is unclear, but thrombus protrusion from the giant aneurysm into the parent artery may have been involved.

Arterial Occlusive Diseases↗
PubMed1990

Mechanisms of absorption of inorganic mercury from rat small intestine. III. Comparative absorption studies of inorganic mercuric compounds in vitro.

The transport of various inorganic mercuric compounds (HgX2s) was compared in everted intestinal sacs and intestinal brush border membrane vesicles (BBMV) of the rat. The preparations were incubated in a medium containing 10(-4) M HgX2 at pH 5.5, 6.4 or 7.4, respectively. The order of transport through the intestinal wall at each pH (HgOAc)2 greater than HgCl2 greater than Hg(SCN)2 greater than HgBr2 greater than Hg(CN)2) was the reverse order of their stability constants, and an increase in pH tended to increase the transport of HgX2. In the experiment with BBMV, similar results were obtained except for the transport of Hg(CN)2. These results suggest that the extent of transport of a certain HgX2 depends on its stability constant, and that the increase in pH promotes the transport possibly as a result of the conversion of HgX2 to Hg(OH)X and Hg(OH)2.

Animals↗
PubMed1990

Difference in effect of sodium selenite on mercury distributions after duodenal administration of mercuric chloride and mercuric oxide.

To obtain evidence for difference in the absorptive forms of HgCl2 and HgO from duodenum, the Hg distributions after the duodenal administration of HgCl2 and HgO and the effect of Na2SeO3 on their Hg distributions were compared. The Hg concentrations in erythrocytes and liver 2 hr after the administration of HgCl2 were significantly lower and higher than those of HgO, respectively, but their Hg distributions at 3.5 or 5 hr became identical. The administration of Na2SeO3 (intravenously) 2 hr after the administration of HgCl2 and HgO resulted in significant differences in their Hg concentrations in plasma, erythrocytes and kidney at 3.5 or 5 hr. These results suggest that the absorptive form of HgCl2 from the duodenum differs from that of HgO and this difference is a cause for the marked difference in effect of Na2SeO3 on the Hg distributions of HgCl2 and HgO.

Animals↗