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Biomedical subjects

F Sato

Publications and source records attributed to F Sato.

At least 271 records · Page 15Linked to original sources
PubMed1990

[Clinical analysis of renal cell carcinoma with intravenous tumor thrombus].

We reviewed treatment and prognosis in 7 operative and 7 non-operative cases of renal cell carcinoma with venous tumor thrombosis formation, 14 cases in total. Treatment after around 1983 involved the use of biological response modifier (BRM), chiefly interferon (IFN), and operation by thoracoabdominal approach. Before that, chemotherapy, radiotherapy and operation by peritoneal approach were used, with many cases judged inoperable. Even in non-operative cases, life-prolongation was frequently achieved by embolization of the renal artery and administration of various BRMs. On the other hand, in cases judged operable which were always treated by resection, early postoperative death sometimes occurred. These facts brought home to us the difficulty of choosing appropriate treatment. Though it is hard to determine the relative merits of various treatments from the present data, since the series is small and contains cases from 1963 onwards, the clinical and pathological pictures should be carefully evaluated for each case, and the most suitable course of treatment should be selected individually. We describe a non-operative case in which a combined use of embolization, IFN-gamma and tumor necrosis factor (TNF) elicited a lasting partial response, and an operative case in which postoperative complications such as pulmonary infarction and renal failure occurred after operation under extracorporeal circulation and patient died at 2 months after operation.

Aged↗
PubMed1990

Thermodynamic study of protein dynamic structure in the oxygen binding reaction of myoglobin.

We examined the flash photolysis of oxy complexes of sperm whale myoglobin (Mb) on the nanosecond time scale at ambient temperatures. In this time range, we can observe the geminate reaction of Mb with the O2 ligand existing in the protein matrix after the photodissociation from the heme iron. We found that the fraction of the geminate component to the total O2 photodissociation exhibited temperature dependences. The geminate fraction decreased with rising temperature, indicating that the protein fluctuation is enhanced at high temperature because of thermal agitation. However, the temperature-dependent behavior showed a break at 20 degrees C. Concerning the geminate O2 escaping reaction from the protein matrix to the solvent region, the activation energy above 20 degrees C (0.4 +/- 0.4 kcal/mol) is significantly lower than that below 20 degrees C (5.1 +/- 0.4 kcal/mol). Thermodynamic analysis on the basis of the transition state theory indicated that the O2 escaping reaction above 20 degrees C is entropy dominated whereas that below 20 degrees C is enthalpy dominated. The results were qualitatively compatible with the theoretical prediction by J. Kottalam and D. A. Case [1988) J. Am. Chem. Soc. 110, 7690-7697). Comparing the kinetic and thermodynamic process of the O2 geminate reaction among several Mbs, we concluded that the geminate O2 reaction with Mb is governed by the dynamic motion of the protein which is sensitively controlled by the static interaction of the heme moiety with the surroundings.

Animals↗
PubMed1990

Enhanced survival of cultured dopamine neurons by treatment with soluble extracts from chemically deafferentiated striatum of adult rat brain.

A soluble fraction was extracted from a chemically deafferentiated striatum of adult Wistar rats after unilateral lesioning of the nigrostriatal pathway by 6-hydroxydopamine (6-OHDA) injection. The soluble extract from the lesioned side enhanced the survival of cultured mesencephalic dopamine (DA) neurons of 14-day-old rat embryos as evidenced by quantitative counting of tyrosine hydroxylase-like immunoreactive cells. The neurotrophic activity of this striatal extract for DA neurons was highest 14 days after 6-OHDA injection and became negligible in 28 days. The extract showed no promoting effects on cultured gamma-aminobutyric acid (GABA)-containing mesencephalic neurons. These observations indicate that the striatum of adult rats may initiate de novo synthesis of trophic substance(s) for DA neurons but not for GABA neurons when subjected to nigral dopaminergic deafferentiation.

Afferent Pathways↗
PubMed1990

Cooperativity between platelet-activating factor and collagen in aggregation of bovine platelets III.

In cooperative aggregation of bovine platelets induced by simultaneous addition of PAF and collagen at subthreshold concentrations the following observations were made. (i) Formation of phosphatidic acid and arachidonic acid metabolites, which characterize PAF and collagen alone-induced aggregation, respectively, was observed very obviously. (ii) A thromboxane antagonist did not completely block the cooperative aggregation. The extent of residual aggregation activity was dependent on concentration of collagen used in the simultaneous administration with PAF. These results suggest that both signal transduction pathways activated by PAF and collagen alone at high concentrations are attained by simultaneous addition of both agonists at subthreshold concentrations through unknown mechanisms.

Animals↗
PubMed1990

Feedback regulation of platelet function by 12S-hydroxyeicosatetraenoic acid: inhibition of arachidonic acid liberation from phospholipids.

We have proposed a mechanism that platelet aggregation is regulated by its 12-lipoxygenase product, 12S-hydroxyeicosatetraenoic acid (12-HETE) (Sekiya, F., Takagi, J. and Saito, Y. (1989) Thrombos. Res. 56, 407-415). Inhibition of endogenous 12-HETE production by 15-HETE, a specific inhibitor of 12-lipoxygenase, accelerated aggregation of bovine platelets in response to collagen and arachidonic acid liberation from phospholipids was enhanced. Exogenously added 12-HETE suppressed collagen-induced liberation of arachidonic acid and the aggregation was also inhibited. On the other hand, 12-HETE did not interfere with thromboxane synthesis from free arachidonic acid in a cell-free system. These observations suggest that 12-HETE exerts a negative feedback to prevent excess aggregation through interference with arachidonic acid liberation from membrane phospholipids.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

Free-radical reactions induced by OH-radical attack on cytosine-related compounds: a study by a method combining ESR, spin trapping and HPLC.

Free-radical reactions induced by OH-radical attack on cytosine-related compounds were investigated by a method combining ESR, spin trapping with 2-methyl-2-nitrosopropane and high-performance liquid chromatography (HPLC). Cytidine, 2'-deoxycytidine, cytidine 3'-monophosphate, cytidine 5'-monophosphate, 2'-deoxycytidine 5'-monophosphate and their derivatives, of which 5,6-protons at the base moiety were replaced by deuterons, and polycytidylic acid (poly(C] were employed as samples. OH radicals were generated by X-irradiating an N2O-saturated aqueous solution. Five spin adducts were separated by HPLC. Examination of them by ESR spectroscopy and UV photospectrometry showed that spin adducts assigned to C5 and C6 radicals due to OH addition to the 5,6 double-bond, a deaminated form of the spin adduct derived from a C5 radical due to the cyclization reaction between C5' of the sugar and C6 of the base, and a spin adduct assigned to the C4' radical due to H abstraction by OH radicals were produced. From these results the sites of OH-radical attack and the subsequent radical reactions in cytosine-related compounds were clarified.

Chemical Phenomena↗
PubMed1990

New transient species of sperm whale myoglobin in photodissociation of dioxygen from oxymyoglobin.

We carried out the flash photolysis of oxy complexes of sperm whale myoglobin, cobalt-substituted sperm whale myoglobin, and Aplysia myoglobin. When the optical absorption spectral changes associated with the O2 rebinding were monitored on the nanosecond to millisecond time scale, we found that the transient spectra of the O2 photoproduct of sperm whale myoglobin were significantly different from the static spectra of deoxy form. This was sharply contrasted with the observations that the spectra of the CO photoproduct of sperm whale myoglobin and of the O2 photoproducts of cobalt-substituted sperm whale myoglobin and Aplysia myoglobin are identical to the corresponding spectra of their deoxy forms. These results led us to suggest the presence of a fairly stable transient species in the O2 photodissociation from the oxy complex of sperm whale myoglobin, which has a protein structure different from the deoxy form. We denoted the O2 photo-product to be Mb*. In the time-resolved resonance Raman measurements, the nu Fe-His mode of Mb* gave the same value as that of the deoxy form, indicating that the difference in the optical absorption spectra is possibly due to the structural difference at the heme distal side rather than those of the proximal side. The structure of Mb* is discussed in relation to the dynamic motion of myoglobin in the O2 entry to or exit from the heme pocket. Comparing the structural characteristics of several myoglobins employed, we suggested that the formation of Mb* relates to the following two factors: a hydrogen bonding of O2 with the distal histidine, and the movement of iron upon the ligation of O2.

Animals↗
PubMed1990

Solubilization and characterization of leukotriene B4 receptor-GTP binding protein complex from porcine spleen.

A high amount of leukotriene B4 (LTB4) binding protein was observed in the porcine spleen. It was solubilized and partially purified from spleen membrane with 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS). Scatchard analysis indicated the presence of a single class of receptor with Kd and Bmax values of 0.26 nM and 120 fmol/mg protein, respectively. The receptor was specific for LTB4, and Ki values for 20-hydroxy- and 20-carboxy-LTB4, both inactive metabolites of LTB4, were 1.7 nM and over 1,000 nM, respectively. By the addition of 10 microM GTP gamma S, a low affinity binding site appeared with a Kd value of 390 nM. A pretreatment of the receptor-GTP binding protein complex with islet-activating protein (IAP) increased the inhibitory effect of GTP gamma S on LTB4 binding, indicating that the LTB4 receptor is coupled with an IAP-sensitive GTP-binding protein in the porcine spleen.

Animals↗
PubMed1990

Some newly synthesized leukotriene B4 analogs inhibit LTB4-induced lysozyme release from rat polymorphonuclear leukocytes.

Antagonistic activities of newly synthesized LTB4 analogs, which possess the same olefinic geometry and the same hydroxyl group stereochemistry as natural LTB4, were investigated by studying lysozyme release from rat polymorphonuclear leukocytes (PMNLs). 14,15-Dihydro LTB4(LTB3) induced lysozyme release from PMNLs as well as LTB4, while 14,15-dehydro LTB4 did not cause lysozyme release but instead clearly inhibit LTB4-induced lysozyme release. Compounds containing aminocarbonyl groups partially retained lysozyme releasing activity. A displacement of the hydrocarbon chain at C13-20 by cyclohexenyl and beta-cyclohexylethyl groups had little effect on lysozyme release, but did strongly inhibit release induced by LTB4. These results may be useful in developing LTB4 antagonists.

Animals↗
PubMed1990

Synthesis and antiinflammatory activity of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11-oxodibenzo[b,e]thiepinacetic and -oxepinacetic acids.

A series of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11- oxodibenzo[b,e]thiepinacetic acids (6-9) and -oxepinacetic acids (10-13) were prepared and their antiinflammatory activity was examined in the rat carrageenan hind paw edema test. The antiinflammatory activity of these compounds depended on their stereochemical features (C6a, C10a, and C2'). The 6a,10a-trans compounds exhibited considerable antiinflammatory activity, whereas the 6a,10a-cis compounds were inactive. Among the trans compounds, 6,6a,7,8,9,10,10a,11-octahydro-11-oxodibenzo[b,e]thiepin-3-p ropionic acid (9a) and its oxepin analogue (13a) showed an antiinflammatory activity superior to that of indomethacin. The phenethyl ester (25) of 9a showed potent antiinflammatory activity, and its safety index (UD50/ED50) was over 14 times higher than that of indomethacin. The phenethyl ester (25) is the most favorable compound with high antiinflammatory activity and little ulcerogenicity.

Animals↗
PubMed1990

Dose and dose-splitting effects of X-rays on lung tumour induction in mice.

This paper reports lung-tumour induction 12 months after single or split doses of X-rays in C3H/He male mice. The early proliferative response of lung cells after doses which induced lung tumours was also examined after single X-irradiation. The lung-tumour incidence tended to increase with increasing dose after a single irradiation and peaked at 5 Gy. At more than 10 Gy it decreased sharply to the control level. The mean tumour diameters tended to increase with doses up to 7.5 Gy and then decreased beyond 10 Gy. These results suggested that suppression of tumour growth reduced the tumour incidence at doses of over 10 Gy. The lung-tumour incidence decreased with increasing intervals between two equal doses of 2.5 or 5 Gy. The decrease was thought to be caused by the repair of the tumorigenic injury. However, the tumour incidence after two 2.5 Gy irradiations at 1 day intervals or two 5 Gy irradiations at 6 h intervals was higher than that observed after a single dose. This phenomenon was regarded as a progression of the tumorigenic injury. The labelling indices of the lung cells, determined using tritiated thymidine after a single irradiation, were higher than those of non-irradiated control cells. This response was delayed as the dose increased. The responses versus days after irradiation could be classified into three patterns on the basis of their peaks. The possibility that the larger delay after higher doses had some relation to the reduction of target cells for tumour incidence is suggested.

Animals↗
PubMed1990

Pharmacological responsiveness of dissociated native and cultured eccrine secretory coil cells.

Methacholine (MCh)- and isoproterenol (Iso)-stimulated 14CO2 production was compared between freshly dissociated rhesus sweat secretory coil cells (mainly clear cells) and cultured cells (grown on a collagen-coated plastic plate) derived from native cells. 14CO2 production was enhanced by MCh and by Iso in native coil cells (but not in ductal cells) in a pharmacologically specific and dose-dependent manner. 14CO2 production in subcultured coil cells (19-45 days in culture) was only one-third to one-fifth that of native cells. MCh-stimulated 14CO2 production was inhibited by ouabain and furosemide in both native and cultured coil cells. A decrease in 14CO2 production, of about one-half, was already evident in primary cells cultured for less than 1 wk. The decreased pharmacological responsiveness of the cultured coil cells was seen, although the cultured cells showed the typical epithelioid appearance, abundant mitochondria, the occasional presence of intercellular lacunae resembling intercellular canaliculi, and the persistence of immunoreactive keratin. We conclude that 1) a primary culture of sweat gland cells can be initiated from dissociated cells; 2) cultured sweat secretory coil cells qualitatively, but not quantitatively, retain the pharmacological responsiveness and transport activity of the native cells as determined by 14CO2 production; 3) collagenase-dissociated cells represent an excellent in vitro system for the study of glandular function at the cellular level; and 4) the decrease in pharmacological responsiveness is not simply due to trypsin treatment during harvesting of cultured cells, because that of organ-cultured, intact, secretory coils also declines with time of culture.

Animals↗
PubMed1990

Functional and morphological changes in the eccrine sweat gland with heat acclimation.

Three adult male patas monkeys (11-15 kg) were heat acclimated by continuous exposure to an ambient temperature of 33 +/- 1 degree C at 13% relative humidity for 9 mo. During the last month, they were also exposed to 45 degrees C at 10% relative humidity for 4 h/day and 5 days/wk. Before and after 3 wk of acclimation, the animals were given a heat-tolerance test in which rectal (Tre) and mean skin (Tsk) temperatures, heart rate, and sweat rate (msw) were monitored during a 90-min exposure to 45 degrees C heat with 24% relative humidity under lenperone (1.0-1.4 mg/kg im) tranquilization. Maximal in vivo msw was also determined in response to subcutaneous injections (1 and 10% solutions) of methacholine (MCh). Before and after 9 wk and 9 mo of acclimation, sweat glands were dissected from biopsy specimens of the lateral calf, cannulated, and stimulated in vitro with MCh. Morphological measurements of isolated tubules were compared with maximal secretory rates produced by MCh stimulation. Three weeks of acclimation 1) reduced Tre and Tsk and increased msw during the heat tolerance test and 2) significantly increased maximal msw in response to MCh stimulation. Acclimation also increased (P less than 0.05) sweat gland size, as measured by tubular length and tubular volume. Maximal in vitro msw produced by MCh stimulation and msw per unit length of secretory coil also increased significantly. We conclude that heat acclimation increases the size of eccrine sweat glands and that these larger glands produce more sweat. They are also more efficient because they produce more sweat per unit length of secretory coil.

Acclimatization↗
PubMed1990

Normalization of impaired coronary circulation in hypertrophied rat hearts.

We tested the hypothesis that impaired coronary autoregulation, decreased flow reserve, and diminished reactive hyperemic response in hypertrophied hearts with coronary arterial hypertension may be reversible after relief of pressure overload. In 4-week ascending aortic banded rats, in vivo peak systolic left ventricular pressure increased to 178 +/- 8 mm Hg (103 +/- 6 mm Hg in sham-operated control group). This increased pressure produced myocardial hypertrophy, and the left ventricular weight/body weight ratio was 46% above that of the control group. After the rats were killed, the coronary perfusion pressure-flow relations were obtained during resting conditions and maximal vasodilation after a 40-second period of ischemia in beating but nonworking isolated hearts perfused with Tyrode's solution with bovine red blood cells and albumin. In hearts from control rats, coronary autoregulation (i.e., a slight decrease in flow with reduction of pressure) was observed in the range of 50-100 mm Hg of perfusion pressure. A pronounced reactive hyperemic response was observed: a peak flow/resting flow ratio of 2.9 +/- 0.1 and a repayment ratio of 1.7 +/- 0.2 at 100 mm Hg of perfusion pressure. In hearts of banded rats the resting pressure-flow relation was rectilinear in the range of 25-175 mm Hg of perfusion pressure. Flow reserve and the time of reactive hyperemia to one half peak flow decreased at 50, 100, and 150 mm Hg of perfusion pressure compared with values in control rat hearts. Four weeks after debanding, peak systolic left ventricular pressure and cardiac hypertrophy had normalized. The impaired autoregulation, decreased flow reserve, and diminished reactive hyperemic response had completely reversed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Atrial natriuretic peptide in patients with the syndrome of inappropriate antidiuretic hormone secretion and with diabetes insipidus.

To examine a possible role for atrial natriuretic peptide (ANP) in water and sodium metabolism disturbances associated with abnormal vasopressin (AVP) secretion, we measured plasma ANP concentrations in 15 patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and in 17 patients with central diabetes insipidus (DI). The mean plasma ANP concentration (30.2 +/- 10.4 pmol/L) in SIADH patients who had hyponatremia, plasma hypoosmolality, hyperosmolar urinary compared to plasma sodium levels, and increased plasma AVP levels relative to plasma osmolality was significantly higher than that in normal subjects (12.6 +/- 4.9 pmol/L), although there was a considerable individual variation in plasma ANP ranging from normal to clearly elevated levels (15.1-47.0 pmol/L). When hyponatremia was corrected by water restriction or demeclocycline administration, plasma ANP levels decreased significantly and fell into the normal range (12.5 +/- 4.3 pmol/L). DI patients who complained of polyuria and polydipsia and had hypoosmolar urine, normal or elevated plasma sodium concentrations, and decreased plasma AVP levels relative to plasma osmolality, on the other hand, had a significantly lower mean plasma ANP level (7.6 +/- 2.9 pmol/L) than normal subjects. There was, again, a considerable overlap between plasma ANP levels in individual DI patients (4.2-13.9 pmol/L) and those in normal subjects. Treatment with 1-desamino-8-D-arginine vasopressin resulted in a significant increase in the mean plasma ANP level (18.6 +/- 8.0 pmol/L). There were no significant correlations between plasma ANP and AVP levels in either group of patients. The results indicate that ANP secretion is modulated by changes in plasma volume consequent to abnormal AVP secretion, which may have a pathophysiological significance in maintaining volume homeostasis.

Adolescent↗
PubMed1990

An analysis of experimental radiation carcinogenesis with model setting for competing risks.

The mean life span of animals killed by a specific type of tumor and the incidence of that particular tumor are influenced by competing risks. A parametric approach for censored samples was applied to correct for the competing risks. The life span distribution under each risk wherein the other risks were thought to be eliminated is assumed to be a Weibull distribution. Our data were from an experiment on tumor induction by X-rays in mice: whole body irradiation with 600 R; head with 800 R; trunk with 800 R; or lower body with 800 R. Analysis of the results shows that the mean appearance time of malignant lymphomas was accelerated by whole body irradiation. Acceleration of lung tumors was relatively large after trunk irradiation. Mammary tumors were accelerated by whole body, trunk or lower body irradiation.

Animals↗
PubMed1990

Effects of 3'-deoxyadenosine (cordycepin) on the repair of X-ray-induced DNA single- and double-strand breaks in Chinese hamster V79 cells.

The ability of cordycepin to inhibit the repair of DNA strand breaks was examined with X-irradiated Chinese hamster V79 cells in log-phase culture. A filter elution technique revealed that 70 microM cordycepin did not inhibit the repair of single-strand breaks but inhibited the repair of double-strand breaks. These findings confirmed the fact that the increase in the lethality of cordycepin in X-irradiated cultured mammalian cells was attributable to unrepaired DNA double-strand breaks.

Animals↗