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Biomedical subjects

K Kishida

Publications and source records attributed to K Kishida.

At least 73 records · Page 4Linked to original sources
PubMed1989

Quantitative analysis of systolic blood pressure tracking during childhood and adolescence using a tracking index: the Shimane Heart Study.

We used a tracking index to carry out a quantitative analysis of blood pressure tracking in children and adolescents. The index was calculated according to changes in blood pressure quintiles for the whole population during the observation period. The study population consisted of 463 Japanese children living in Izumo, who were examined every 3 years from 6 to 12 years of age in cohort 1, and from 9 to 15 years of age in cohort 2. In both sexes, the tracking index decreased transiently during the period from 9 to 12 years of age and increased again thereafter. The index was higher in girls than in boys except for the period from 12 to 15 years. Correlation coefficients between blood pressure at the first and that at the second examination increased with age in both sexes. We conclude that the tracking index could quantify the degree of tracking. Systolic blood pressure tracked well during childhood and adolescence, and the degree of tracking increased after the age of 12 years in both sexes.

Adolescent↗
PubMed1988

Nature of linkage and mode of action of methotrexate conjugated with antitumor antibodies: implications for future preparation of conjugates.

The binding of methotrexate (MTX) to IgG in conjugates was examined by studies on a direct MTX conjugate with a monoclonal antibody (aMM46) to mouse mammary tumor MM46 cells and corresponding irrelevant antibody and normal gamma-globulin conjugates, all prepared by the active ester method with MTX N-succinimidyl ester (MTX-OSu). The binding was examined in terms of effects on the potency and selectivity of the cytotoxic activity of the aMM46 conjugate. The results obtained supported the following conclusions: (a) MTX-OSu reacts not only with the amino group of IgG to give an amide bond, but also with another group(s) to give a less stable bond(s) such as an ester bond; (b) in contrast to the amide bond-linked MTX, which is taken up by the cells by endocytic internalization, a substantial portion of the MTX linked by an ester or other less stable bond(s) is released from the conjugates extracellularly and enters the cells by the MTX active transport system, as revealed by the inhibitory effect of thiamine pyrophosphate on the cytotoxicity; (c) this MTX linked by a less stable bond(s) that causes nonspecific cytotoxicity can be removed by treatment with hydroxylamine; (d) the overall cytotoxicity of aMM46-MTX decreased on removal of this less stably linked MTX, suggesting that the lysosomal degradation of the conjugate carrying amide bond-linked MTX to liberate MTX derivatives of low molecular weight is insufficient; (e) the liberation of low-molecular-weight substances in the lysosomes is probably more important for efficient entry of active substances into the cytosol, than for inhibition of the activity of dihydrofolate reductase, because after hydroxylamine treatment, the amide bond-linked MTX showed greater decrease in drug cytotoxicity than in inhibitory activity against dihydrofolate reductase; (f) in combination with hydroxylamine treatment, insertion between MTX and IgG of a linkage capable of ready cleavage in lysosomes deserves exploitation as a method for making potent conjugates with less nonspecific activity.

Animals↗
PubMed1988

Endogenous inhibitor of ecdysone synthesis in crabs.

Attempts to isolate the molt-inhibiting hormone (MIH) of crustaceans from crab eyestalks (ES) resulted in the characterization of xanthurenic acid as an inhibitor of ecdysone biosynthesis in the cultured Y-organ-complex (YOC) homogenate. It was also found that 3-hydroxy-L-kynurenine present in the ES is transformed into xanthurenic acid in the YOC and body fluid. Its mode of inhibitory action in ecdysone biosynthesis is probably inactivation of cytochrome P-450.

Animals↗
PubMed1988

Prevalence of human immunodeficiency virus (HIV) infection among hemophiliacs in Fukuoka, Japan.

To determine when the hemophiliacs in Fukuoka prefecture, Japan, first became positive for antibodies, we tested human immunodeficiency virus (HIV) antibodies on serum samples obtained from 1976-1987 stored at -30 C. Fifteen out of 64 hemophilia A patients (23.4%), five out of 11 hemophilia B patients (45.5%), but none of 17 patients with von Willebrand's disease (0%) were positive for HIV antibodies. In this series, two with hemophilia A became positive for HIV antibodies for the first time in 1983, and in 1984 another four with hemophilia A and one with hemophilia B became positive.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Effect of heart rate on the end-systolic wall stress-mean velocity of circumferential fiber shortening relation.

The correlation of left ventricular end-systolic wall stress (ESS) with the mean velocity of fiber shortening (mVcf) is an index of the myocardial contractile state, independent of the ventricular loading conditions (afterload). However, there have been few reported estimates of the effect of changes in the heart rate on the ESS-mVcf relationship. In the present study, 25 subjects with histories of Kawasaki disease (mucocutaneous lymph node syndrome: MCLS) were evaluated for the effects of changes in heart rate, afterload and preload, on the ESS-mVcf relationship. The latter was independent of afterload. After atrial pacing, ESS decreased and mVcf increased, both significantly, compared to those of subjects at rest. The change of the ESS-mVcf relationship induced by atrial pacing approximately paralleled the mean regression line obtained in the resting state. However, the shift induced by preload was not parallel to the mean regression line for the resting population. These data suggest that the ESS-mVcf relationship is independent of any change in heart rate, and that it may depend on preload.

Cardiac Catheterization↗
PubMed1988

Diastolic left ventricular function in normal children: the maximal positive dD/dt compared with the E/A ratio of mitral flow pattern.

The normal values for left ventricular diastolic function in children are influenced by numerous factors. As an index of this function, the maximum velocity of left ventricular internal dimension expansion (+ max dD/dt) was calculated from M-mode echocardiography for 33 normal persons who ranged in age from seven days to 18 years. This index showed a linear correlation with left ventricular end-diastolic dimension in the resting state. This index was compared with the E/A ratio which is ordinarily used as the diastolic functional index for children. Considering changes in physical development during childhood, both indices showed similar trends in relation to body surface area. The E/A ratio was strongly influenced by heart rate, but + max dD/dt was not. This was the major difference between two indices.

Adolescent↗
PubMed1987

In vitro cytotoxicity of a human serum albumin-mediated conjugate of methotrexate with anti-MM46 monoclonal antibody.

In studies on antitumor antibody:drug conjugates as potential antitumor agents, methotrexate (MTX) was conjugated with a murine monoclonal antibody (aMM46) to an antigen on ascitic mouse mammary tumor MM46 cells (MM antigen) with human serum albumin (HSA) as an intermediary. MTX was linked to HSA which had been conditioned to have about 1 mol of thiol group per mol of HSA by dithiothreitol treatment followed by oxidation on standing at 4 degrees C. The MTX linking was performed, without protection of the thiol group of HSA, by using MTX N-succinimidyl ester prepared via MTX intramolecular anhydride. The resulting HSA:MTX was reacted with the immunoglobulin with the maleimide group introduced. The aMM46:HSA:MTX obtained retained both antibody binding and drug activities. The cytotoxicity of aMM46:HSA:MTX against MM antigen-positive MM46 cells was greater than that of control 96.5 (anti-human melanoma-associated antigen, p97):HSA:MTX and was inhibited by unconjugated aMM46. No different cytotoxicity of aMM46:HSA:MTX compared with that of 96.5:HSA:MTX was observed against MM antigen-negative mouse mammary tumor MM48 cells. The presence of ammonium chloride or leupeptin abrogated the selective cytotoxicity against MM46 cells of aMM46 conjugate but did not affect the nonspecific cytotoxicity of 96.5:HSA:MTX. These results support the idea that the selective cytotoxicity of aMM46:HSA:MTX is antibody directed and exhibited through lysosomal degradation of the conjugate.

Ammonium Chloride↗
PubMed1987

Target-selective cytotoxicity of methotrexate conjugated with monoclonal anti-MM46 antibody.

In studies on antitumor antibody-cytotoxic drug conjugates as potential tumor-selective cytotoxic agents, methotrexate (MTX) was conjugated via its active ester derivative with a murine monoclonal antibody (aMM46) to a mouse mammary tumor antigen (MM antigen) on syngeneic, ascitic C3H/He mouse mammary tumor MM46 cells. The conjugate retained full antibody activity, as assayed by complement-dependent cytolysis. The target-selective cytotoxicity of aMM46-MTX was verified by the observations that this conjugate showed greater cytotoxicity than the corresponding normal mouse immunoglobulin (nIg) conjugate to MM46 cells, neither aMM46 nor nIg being cytotoxic, and that it showed less cytotoxicity to MM antigen negative mouse mammary tumor MM48 cells than to MM46 cells, its cytotoxicity to MM48 cells being similar to that of the nIg conjugate. From the results of assays of cell binding and uptake of 131I-labeled aMM46 and aMM46-3H-MTX, aMM46 and aMM46-MTX were internalized after their binding to MM46 cell surface antigen. Leupeptin, an inhibitor of the lysosomal endopeptidase cathepsin, decreased the cytotoxicity of aMM46-MTX, supporting the involvement of lysosomal degradation of the conjugate in its action.

Animals↗
PubMed1987

Quantification of blood pressure tracking of children by tracking index: the Shimane Heart Study.

The tracking of systolic blood pressure (SBP) was analyzed in a cohort of children. The study population consisted of 1009 Japanese children in Izumo City, a rural community in the northwest of Honshu. There were 252 subjects in cohort (C)-1, 235 in C-2, 286 in C-3, 131 in C-4 and 105 in C-5. Follow-up periods were from 6 to 9 years of age in C-1, 9 to 12 in C-2, 12 to 15 in C-3, 6 to 12 in C-4 and 9 to 15 in C-5. BP was measured by conventional method. Tracking index (TI) was calculated as follows: TI = (2x + y - z)/N/.24; x, y and z are numbers of subjects who remained at the same quintile, who moved to the next quintile and who moved to a remote quintile, respectively; N = x + y + z; TI becomes 1.0 when SBP changes randomly. SBP tracking was apparent in both sexes of C-1 (TI = 2.4 in boys, 2.5 in girls), in girls of C-2 (TI = 3.5), in both sexes of C-3 (TI = 3.2 in boys, 2.7 in girls) and in girls of C-4 (TI = 4.1) and C-5 (TI = 3.3). TI agreed well with the tracking phenomena visualized by distribution bar graph. We conclude that TI can assess the degree of tracking quantitatively and can be applied to analysis of the tracking phenomena of BP and its related factors.

Blood Pressure↗
PubMed1987

Induction of cytochrome P-450 in the rabbit eye by phenobarbital, as detected immunohistochemically.

The present study was aimed to demonstrate that cytochrome P-450 was induced by drug administration in particular tissues in the eye. Phenobarbital was used as an inducer. We showed immunohistochemically that cytochrome P-450 was induced in the cornea, conjunctiva and ciliary epithelium of rabbits after four days of intraperitoneal administration of phenobarbital at a dose of 80 mg per kg per day. We did not detect significant immunofluorescence in other ocular tissues. Prolonged administration caused degeneration of the ciliary epithelium, but not pathological change was seen in other ocular tissues. In this case, immunofluorescence was not detected in the ciliary epithelium but in the cornea, conjunctiva and lens.

Animals↗
PubMed1987

Dome formation in cell cultures of chick embryo retinal pigment epithelium and effects of ouabain and 2,4-dinitrophenol thereon.

Cells from chick embryo retinal pigment epithelium were cultured on glass slips. The primary culture cells formed confluent cell layers which were studded with a number of domes. The domes had usually appeared by the fourth day of culture and were susceptible to 3 X 10(-6) M ouabain and 10(-4) M 2,4-dinitrophenol, indicating that fluid was transepithelially transported from the apical to the basal side by means of an energy-requiring and ouabain-sensitive mechanism. Other than domes, small blisters appeared after 4-10 days of culture. They were also susceptible to the metabolic inhibitors.

2,4-Dinitrophenol↗
PubMed1986

ATPases of ciliary epithelium: cellular and subcellular distribution and probable role in secretion of aqueous humor.

The distribution of ion-stimulated ATPases of the ciliary epithelium has been examined in tissues from bovine and rabbit eyes. In homogenates of tissues from both species, both Na,K- and anion-stimulated enzyme activities were found, but no K,H-stimulated activity was detected. The anion ATPase had a broad specificity for a number of anions, and was strongly inhibited by thiocyanate. Following separation of pigmented (outer) and non-pigmented (inner) layers of the bovine ciliary epithelium and isolation of the two cell types on density gradients, higher activities of both Na,K- and anion ATPases were found in the non-pigmented cells. Subcellular fractionation of a mixed population of cells showed that the anion ATPase was almost exclusively associated with a mitochondrial fraction, rather than with the plasma-membrane fraction containing the Na,K-ATPase. These results confirm histochemical studies of the distribution of Na,K-ATPase in the ciliary epithelium and support the concept that the inner, non-pigmented cell layer is chiefly responsible for the active transport of ions into the posterior chamber. It is concluded that this transepithelial transport can be driven only by the energy derived via the Na,K-ATPase, and that any subsequent anion or proton transport in the formation of aqueous humor is driven by the sodium gradient through exchange mechanisms.

Adenosine Triphosphatases↗
PubMed1986

2-Substituted 1, 3, 4-thiadiazole-5-sulfonamides as carbonic anhydrase inhibitors: their effects on the transepithelial potential difference of the isolated rabbit ciliary body and on the intraocular pressure of the living rabbit eye.

In order to understand the pharmacology of carbonic anhydrase inhibitors in reduction of aqueous secretion, three sorts of studies were conducted using five 2-substituted 1, 3, 4-thiadiazole-5-sulfonamides: an inhibition study of carbonic anhydrase II, electrical measurements of the isolated ciliary body, and pharmacological study on intraocular pressure of living animals. The inhibitors of carbonic anhydrase employed here were 2-amino-1, 3, 4-thiadiazole-5-sulfonamide; 2-methylamino-1, 3, 4-thiadiazole-5-sulfonamide; 2-formylamino-1, 3, 4-thiadiazole-5-sulfonamide; 2-acetylamino-1, 3, 4-thiadiazole-5-sulfonamide (acetazolamide); and 2-propionylamino-1, 3, 4-thiadiazole-5-sulfonamide. All of these compounds showed significant inhibitory activity to carbonic anhydrase II which exists in the ciliary epithelium, but their potencies of inhibition varied relative to one another (I50S were 1.91 X 10(-7) to 3.3 X 10(-8) M). The effects of the five compounds on electrical phenomena were observed using isolated rabbit ciliary body mounted on an Ussing's chamber. Each compound decreased the negative electrical potential of the tissue (-0.70 mV as the average of the initial values) by 10- to 33%, and this effect was proportional to its inhibitory activity to carbonic anhydrase II. The effects of the five compounds on intraocular pressure were determined, and each compound decreased the intraocular pressure (18 mmHg as the average of the initial values) by 7- to 32%. This effect was also proportional to the inhibitory activity to the enzyme. Correlation between the two effects was studied, and good correlation was observed. This implies that both effects have a common basis which relates to the physiological role of carbonic anhydrase. The present study, therefore, shows the importance of the bicarbonate ion in the aqueous humor formation since it is both substrate and product of carbonic anhydrase II.

Acetazolamide↗