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Biomedical subjects

K Ishihara

Publications and source records attributed to K Ishihara.

At least 505 records · Page 28Linked to original sources

[Clinical significance of antibodies against calmodulin in patients with various liver diseases].

The sera from patients with various liver diseases were investigated for the antibody against calmodulin (CaM) extracted from bovine brain by the enzyme linked immunosorbent assay. The specificity and purity of CaM were confirmed by the Western blot technique using anti-CaM antibody (anti-CaM) positive sera. IgA class antibody was frequently detected in patients with hepatocellular carcinoma (HCC), autoimmune hepatitis (AIH) and chronic active hepatitis (CAH). On the other hand, IgG class antibody was very often present in patients liver cirrhosis, AIH and acute viral hepatitis (AVH). Sixty seven percent of patients with AVH in the acute phase were positive for IgM class anti-CaM and 33% of patients with AVH in the convalescent phase positive respectively. In AVH, the titer of anti-CaM reached its peak on 26.3 days after the onset. The titer of anti-CaM in fulminant hepatitis was higher than that in AVH. Seventy percent of type A hepatitis patients were positive for IgM class anti-CaM, 33% of type B and 33% of type non-A non-B. These results suggest that the frequency and titer of anti-CaM may depend upon the type of hepatitis and the degree of liver cell injury.

Autoantibodies↗

[Evaluation criteria for chemotherapeutics for malignant skin carcinomas].

Malignant skin carcinomas occur in a large variety of forms, among them malignant melanoma with a poor prognosis, such as squamous cell carcinoma, basal cell carcinoma, appendix tumors of skin (e.g., sweat gland carcinoma, sebaceous gland carcinoma), metastatic carcinomas of skin, intraepidermal carcinomas (e.g., Bowen's disease, Paget's disease) and mesenchymal carcinomas including mycosis fungoides (cutaneous T cell lymphoma). Furthermore, not only do they present with varied clinical symptoms, some forming tumors or erythemas, some being infiltrative in nature and some being flat in shape, but the clinical symptoms also vary with time during treatment. All these conditions conspire to make the evaluation of chemotherapeutics complicated and difficult. In the field of dermatology topical drugs provide a no less powerful weapon than drugs for systemic administration with which to combat skin carcinomas and are simple and easy to administer. In consideration of those clinical and therapeutic aspects of malignant skin carcinomas new evaluation criteria for chemotherapeutics for topical and systemic administration have been established by adding three-way measurement to the conventional methods of one- and two-way measurement for measurable lesions along with the evaluation of the response of clinical symptoms to chemotherapeutics in unmeasurable carcinomas. The new version of criteria is based in its general framework on the Japan Society for Cancer Therapy's Evaluation Criteria for Chemotherapeutics for Solid Carcinomas by Koyama and Saito and the new version has been approved at the 26th general meeting of the Japan Society for Cancer Therapy (1988, Niigata).

Administration, Cutaneous↗

Anion channels activated by adrenaline in cardiac myocytes.

In heart cells, the catecholamine-activated cyclic AMP system regulates calcium and potassium channels. We report here a novel class of chloride channels that can be activated by adrenaline in mammalian ventricular cells. Like the agonist-activated Cl- channel currents of airway and colonic epithelial cells, the cardiac Cl(-)-channel current shows outward rectification. But the unit conductance of cardiac Cl- channels is smaller than that of epithelial Cl- channels. The cardiac Cl- channel is functionally voltage-independent, in contrast to the Cl- channel in colonic epithelial cells. This channel could be responsible for the beta-catecholamine-induced increase in cardiac membrane conductance that has been attributed to activation of a Cl- current. Thus, sympathetic control of cardiac electrical activity involves not only the voltage-dependent, excitation-related cation channels, but also anion channels that generate a steady current.

Animals↗

Reduced thrombogenicity of polymers having phospholipid polar groups.

The thrombogenicity of polymers having a phospholipid polar group, poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)), was evaluated by a microsphere-column method with attention to the activation and adhesion of platelets on the polymer surface. When citrated platelet-rich plasma (PRP) contacted with the polymers, a large number of platelets adhered and aggregated on poly(BMA). The number of adherent platelets decreased and deformation and aggregation were suppressed with increasing MPC composition. The same tendency was noted when Ca2(+)-re-added PRP came in contact with the polymers. In the case of poly(MPC-co-BMA) with 0.320 mole fraction of MPC, activation of platelets and formation of fibrin were completely suppressed. Therefore, MPC moieties in the polymer play an important role in the reduction of thrombogenicity of the polymer.

Animals↗

Involvement of I-A-restricted B-B cell interaction in the polyclonal B cell differentiation induced by lipopolysaccharide.

The present study has examined a functional role of Ia molecules expressed on murine B cells in polyclonal B cell differentiation induced by lipopolysaccharide (LPS). Reverse, IgM PFC responses of unprimed B cells induced by LPS in the apparent absence of T cells and adherent accessory cells were markedly inhibited in a haplotype-specific manner by Fab monomer fragment of anti-class II (Ia) but not anti-class I MHC monoclonal antibody (mAb). However, the degree of inhibition of LPS responses of H-2-heterozygous F1 B cells expressing both parental I-A products by either one of anti-I-A mAb was at best half that of the parental B cells. Interestingly, when (B10 x B10.-BR)F1 (H-2b/k) B cells were fractionated into adherent and nonadherent populations by their ability to bind to parental B10 B cell monolayers, LPS responses of F1 B cells adherent to and nonadherent to the B10 B cell monolayers were selectively inhibited by anti-I-Ab and anti-I-Ak mAb, respectively. These results suggest that LPS-responsive F1 B cells comprise at least two separate populations with restriction specificity for only one of the parental I-A products expressed on B cells. In addition, it was demonstrated that the I-A-restriction specificity of LPS-responsive B cells is "plastic" and determined by H-2-genotype of bone marrow cells present during B cell ontogeny but not by that of radiation-resistant host elements. Namely, the LPS responses of B10-derived B cells from (B10 + B10.BR) (H-2b x H - 2k)F1 radiation bone marrow chimeras but not from B10 (H-2b x H-2k)F1 chimeras became sensitive to the inhibition of anti-I-Ak mAb in the presence of mitomycin C-treated I-Ak-positive B cells, supporting a notion of receptor-Ia molecules interactions rather than like-like interactions. Thus, the present results provide evidence indicating that B-B cell interaction via recognition of self-I-A products is a crucial event in the polyclonal B cell differentiation induced by LPS.

Animals↗

Different drug-susceptibilities of long-term potentiation in three input systems to the CA3 region of the guinea pig hippocampus in vitro.

The susceptibilities to several drugs of long-term potentiations in the three input systems (mossy, commissural/associational and fimbrial fibres) to CA3 pyramidal neurones were investigated in hippocampal slices from the guinea pig. D-2-Amino-5-phosphonovalerate (D-APV), a selective antagonist at N-methyl-D-aspartate (NMDA) receptors, blocked the long-term potentiations in the commissural/associational fibre- and fimbrial fibre-CA3 systems, but did not significantly affect that in the mossy fibre-CA3 system. The latter was suppressed by kynurenate, a non-selective glutamate receptor antagonist. On the other hand, naloxone, an opioid antagonist, inhibited and bifemelane, which improves metabolism in brain and has an anti-amnesic action, augmented long-term potentiation in mossy fibre-CA3 system but did not influence those in commissural/associational fibre- and fimbrial fibre-CA3 systems. These findings suggest that the mechanisms, relevant to production of long-term potentiation in the mossy fibre-CA3 system, are different from those in the commissural/associational fibre- and fimbrial fibre-CA3 systems. N-Methyl-D-aspartate receptors are involved in the latter systems, while non-NMDA receptors for L-glutamate and opioid receptors are involved in the former. Further, the mossy fibre-CA3 system is more susceptible to a drug, having an anti-amnesic action, than are the other two systems.

2-Amino-5-phosphonovalerate↗

Lack of favorable effect of immunomodulators on outbred syngeneic rodent islet transplantation.

We studied the effect of two immunomodulators, lobenzarit disodium and OK-432, on outbred syngeneic islet transplantation. Six hundred fresh islets taken from two male Wistar rats were transplanted intraportally into other male Wistar rats that had been made diabetic with streptozotocin. Lobenzarit was given to 12 recipients and OK-432 to seven recipients intraperitoneally for 1 month, while nine controls received only intraperitoneal saline. Both drug-treated groups could not maintain lower fasting plasma glucose levels or higher fasting body weights at each time as compared with controls. The islet survival time in lobenzarit-treated (23.5 +/- 8.0 days) and OK-432-treated (25.3 +/- 13.4 days) groups was not longer than that (21.6 +/- 9.4 days) of the control group. All the pancreatic insulin contents of the seven surviving controls, ten surviving lobenzarit and five surviving OK-432 recipients were less than 0.8% of the mean insulin content obtained from 12 normal male rats. The hepatic insulin content of both drug-treated groups was not higher than that of the control group. These results suggest that lobenzarit disodium and OK-432 cannot protect outbred syngeneic islet grafts.

Adjuvants, Immunologic↗

Possible involvement of cholinergic nicotinic receptor in insulin release from isolated rat islets.

Insulin release is influenced by the autonomic nervous system. Regarding parasympathetic control, previous reports have shown that regulation of insulin release is executed exclusively through muscarinic receptors in the pancreatic islets. In the present study, however, we examined the effect on insulin release at the islet level of various agents affecting the parasympathetic nervous system, especially nicotinic receptor blockers. Pancreatic islets isolated from adult Wistar male rats were incubated with these agents and insulin release in the media was measured. Acetylcholine chloride (10(-5) M), as well as distigmine bromide (10(-6), 10(-5) M), both of which are cholinesterase inhibitors, stimulated insulin release, whereas atropine (5 x 10(-6), 5 x 10(-5) M) suppressed it. On the other hand, serum and IgG from myasthenia gravis patients, containing anti-acetylcholine receptor antibodies, affected insulin release, and alpha-bungarotoxin (10(-9)-10(-7) M), a nicotinic receptor blocker, stimulated insulin release dose-dependently. The present observations suggest that insulin release is influenced by the parasympathetic nervous system, mediated via not only muscarinic but also nicotinic receptors.

Acetylcholine↗

Clinical guidelines for the early detection of plantar malignant melanoma.

Of 144 pigmented lesions excised from the soles of Japanese patients, 140 were melanocytic. Apart from congenital melanocytic nevi, only a few benign acquired melanocytic nevi on the sole were more than 7 mm in maximum diameter and none exceeded 9 mm. In contrast, all plantar malignant melanomas, including malignant melanoma in situ, were 9 mm or more in maximum diameter. In addition, the majority of plantar melanocytic lesions excised from patients who were older than 50 years of age were malignant melanoma. On the basis of these data, we propose clinical guidelines for the early detection of plantar malignant melanoma.

Adult↗

Doppler echocardiographic quantitation of cross-sectional area under various hemodynamic conditions: an experimental validation in a canine model of supravalvular aortic stenosis.

The hemodynamic effects on cross-sectional area calculated with the continuity equation were assessed in canine experiments. In 13 open chest dogs, 46 supravalvular aortic stenoses were created by aortic root banding. The cross-sectional area of the stenosis was calculated by Doppler echocardiography with application of the continuity equation before and after the following hemodynamic interventions: protocol 1, atrial pacing at 90, 120, 150 and 180 beats/min after sinus node crush; protocol 2, preload reduction by mild and severe clamping of the inferior vena cava; and protocol 3, afterload augmentation by mild and severe clamping of the descending aorta. In each observation, a dimension of the stenosis was directly measured by two-dimensional echocardiography, and the cross-sectional area was determined as a reference standard. As a result of the hemodynamic interventions, significant changes were observed in stroke volume and pressure gradient (protocol 1), in cardiac output, stroke volume and pressure gradient (protocol 2) and in heart rate, cardiac output and pressure gradient (protocol 3). Despite these changes in hemodynamic variables, the Doppler-derived cross-sectional area showed no significant change for a given stenosis. In addition, areas calculated with the continuity equation (x) agreed well with those determined by two-dimensional echocardiography (y) (r = 0.96, p less than 0.001, y = 0.97x + 0.02, SEE = +/- 0.06 cm2). Thus, it is concluded that Doppler echocardiography with application of the continuity equation accurately predicts the stenotic cross-sectional area over a wide range of hemodynamic conditions in supravalvular aortic stenosis.

Animals↗

B-B cell interaction involved in polyclonal B cell activation is restricted by I-A but not by I-E molecules.

We have previously demonstrated that the class II MHC restricted B-B cell interaction is involved in the polyclonal differentiation of unprimed murine B cells into IgM-producing cells induced by a T cell-derived lymphokine B151-TRF2 or bacterial LPS. The present study has addressed the question of whether I-A and/or I-E molecules function as restriction elements for the B-B cell interaction. The results revealed that (B10 x B10.BR)F1(H-2b/k) B cells could be separated into I-Ab- and 1-Ak-restricted subpopulations by their ability to bind to B10(H-2b) or B10.BR(H-2k) B cell monolayers, whereas an I-E-restricted F1 B cell population was not obtained. Moreover, B10-derived B cells isolated from (B10 + B10.BR) - (B10 x B10.BR)F1 but not from B10 - (B10 x B10.BR)F1 radiation-induced bone marrow chimeras acquired newly the ability to co-operate with mitomycin C-treated auxilary B cells expressing I-Ak but not I-Ek molecules. Thus, these results indicate that I-E molecules, unlike I-A molecules, do not serve as restriction elements for the B-B cell interaction, and that I-A and I-E molecules on B cells play functionally disparate roles in the activation of polyclonal B cells.

Animals↗

Myocardial stiffness derived from end-systolic wall stress and logarithm of reciprocal of wall thickness. Contractility index independent of ventricular size.

The slope of the end-systolic pressure-volume relation (ESPVR) is useful in assessing acute changes in contractile state. However, a limitation of ESPVR is that its slope decreases progressively as ventricular size increases without this change necessarily indicating a change in contractile state. In this respect, an index of contractile function that is independent of ventricular size would have an obvious advantage. The exponential constant (k) of the end-systolic relation between wall stress (sigma) and the natural logarithm of the reciprocal of wall thickness [ln(1/H)], sigma = Cekln(1/H), corresponds to the stiffness constant of the myocardium (kSM), a contractile index that should be independent of ventricular size and geometry. To examine the size independence of kSM, we studied left ventricular kSM during beta-blockade (to stabilize inotropic state) in 25 normal dogs with greatly differing ventricular sizes whose end-diastolic volumes ranged from 14 to 82 ml. The kSM was nearly constant (3.6 +/- 0.4) over this wide range of end-diastolic volumes and thus was independent of end-diastolic volume. Conversely, ESPVR, also obtained during beta-blockade, was closely and negatively correlated to end-diastolic volume (r = 0.92). To test the ability of kSM to measure changes in contractile state, we altered contractile state pharmacologically. The kSM increased from 3.7 +/- 0.5 to 4.8 +/- 0.8 (p less than 0.01) with infusion of dobutamine (after reversal of beta-blockade) and decreased to 3.1 +/- 0.3 (p less than 0.05) with inhalation of isoflurane, a negative inotrope, during beta-blockade (p less than 0.05). We conclude that kSM is independent of ventricular size and is sensitive to changes in inotropic state. As such, it should be useful as an index of contractile function.

Animals↗

[Effects of Shosaiko-to-go-keishikashakuyaku-to (TJ-960) on the valproic acid induced anomalies of rat fetuses].

Shosaiko-to-go-keishikashakuyaku-to (TJ-960) is an extract of nine herbal drugs (Paeoniae radix, Cinna momi cortex, Bupleuri radix, Zingiberis rhizoma, Glycyrrhizae radix, Ginseng radix, Scutellariae radix, Pinelliae tuber and Zizyphi fructus) that has a potent anticonvulsant action. The rat fetuses treated orally with TJ-960 during the organogenesis period (days 7-17 of gestation) revealed no anomalies (up to 3000 mg/kg/day). When TJ-960 was co-administered with sodium valproate (VPA, 400 mg/kg) during the organogenesis period, embryonic resorption, fetal body weight, ossification and skeletal variation or anomalies induced by VPA were markedly reduced. The maternal plasma and embryonic concentration of VPA with TJ-960, however, were not significantly different from VPA alone. These results suggest that TJ-960 has protective effects against the teratogenicity of VPA.

Abnormalities, Drug-Induced↗

Development of artificial model of caval syndrome in canine heartworm disease.

In order to develop an artificial model of caval syndrome (dirofilarial hemoglobinuria), heartworm-like silicone tubes were inserted into the tricuspid valve orifice and right atrium of dogs. Fifteen to 25 tubes with some knots were inserted through the posterior vena cava in 6 dogs (knot-tube group), 7 to 12 tubes without knot (small-number group) through the jugular vein in another 5 dogs, or 25 to 35 tubes (large-number group) in yet another 5 dogs. The tubes remained in the right atrium, and a part of them protruded into the tricuspid valve orifice. The number of tubes at the tricuspid valve orifice was the greatest in the large-number group. After tube insertion, the signs of so-called "caval syndrome", such as systolic cardiac murmur, jugular pulse, anemia, and so on, were observed in almost all cases of the 3 groups, the signs were severest in the large-number group. Urine hemoglobin was detected in almost all cases of the knot-tube and large-number groups, and in 1 case in the small-number group. Ascites was observed in 1 case of the knot-tube group at 6 weeks, in 1 case of the small-number group at 7 days and in 3 cases of the large-number group at 7 days after insertion.

Animals↗

Contribution of live heartworms harboring in pulmonary arteries to pulmonary hypertension in dogs with dirofilariasis.

To investigate whether adult heartworms harboring in the pulmonary arteries contribute to pulmonary hypertension, we determined the cardio-pulmonary values immediately before and after removal of heartworms from the pulmonary arteries and before and after insertion of live worms in their place. In 10 heartworm-infected dogs, 8 to 46 worms were removed. The mean pulmonary arterial pressure fell significantly from 24.5 +/- 7.9 mmHg to 16.3 +/- 4.9 mmHg (p less than 0.01) immediately after removal. The right cardiac output decreased in 7 of the 10 cases. The total pulmonary resistance and right ventricular stroke work index also decreased. At 24 hours after removal, live heartworms were put back into the pulmonary arteries of their host dog. The mean pulmonary arterial pressure elevated significantly (p less than 0.01) immediately after insertion. The right cardiac output further decreased in 7 of the 10 dogs, and the total pulmonary resistance and right ventricular stroke work index increased. Separate from this, 12 to 42 heartworms were transplanted into the pulmonary arteries of 5 heartworm-free dogs. Immediately after transplantation, the pulmonary arterial pressure did not show any significant change. However, the stroke volume decreased, and the total pulmonary resistance increased. These facts suggest a contribution of live heartworms to the pulmonary hypertension, although there is a complicated interaction among the presence of heartworms, the pulmonary lesions and the pulmonary hypertension.

Animals↗