Biomedical subjects
Publications and source records attributed to K Ishihara.
Murine monoclonal antibodies against Treponema denticola were produced. One monoclonal antibody (MSA257) reacted with 34,000 dalton antigens of all T. denticola strains, including ATCC strains and our isolates. This monoclonal antibody also reacted with antigens of other treponema strains tested.
Multiple dark brown papillomatous tumors, showing some histological features of verrucous carcinoma or giant condyloma, developed mainly in the anogenital region of a Japanese woman. The tumors first appeared when she was 51 years old and annoyed her for over 20 years with several recurrences without any frank malignant transformation, after surgery. Immunohistochemically, papillomavirus genus-specific antigen was demonstrated only in small foci of the lesions resected at first operation. Southern blot analysis revealed human papillomavirus type 6b-related DNA in a surgically resected specimen. The possible role of the human papillomavirus in the genesis of this unique tumor is discussed.
1. The blockade by Mg2+ and intrinsic gating of the channel, which underlie the rectification of the inward rectifier K+ current, was investigated using the oil-gap voltage clamp method in isolated guinea-pig ventricular cells. 2. The inward rectifier K+ current was isolated by subtracting trans-gap currents recorded at an extracellular K+ concentration ([K+]o) of 0 mM from those obtained at 14 mM [K+]o in the presence of a given concentration of intracellular Mg2+ ([Mg2+]i). The reversal potential (V0) of the difference current was near the equilibrium potential for K+ (EK). 3. On repolarization across EK, the inward rectifier K+ current showed a rapid exponential increase. The time constant decreased with increasing hyperpolarization, but it was independent of both [Mg2+]i and the preceding depolarization. 4. When the pre-pulse potential was made progressively positive between V0-20 and V0 + 30 mV, the amplitude of the time-dependent component became larger and the preceding current jump decreased at any [Mg2+]i. With pre-pulses more positive than V0 + 40 mV, the time-dependent component started from almost the zero current level at 2 microM [Mg2+]i. At higher [Mg2+]i (350, 500 and 3000 microM), however, the time-dependent component became smaller as the pre-pulse potential was made more positive than V0 + 40 mV. 5. When the membrane was depolarized from a potential of full activation at 2 microM [Mg2+]i, the initial jump in the outward current was ohmic and was followed by an exponential decay. The time-dependent component of the inward current, recorded on repolarization after increasing durations of the preceding depolarization, developed as the outward current decayed. The time constants of both processes were in good agreement. 6. At 500 microM [Mg2+]i, the outward current on depolarization was instantaneously rectified. The time-dependent component recorded on repolarization developed with prolongation of the pre-pulse with a time course slower than at 2 microM [Mg2+]i. The envelope time course became slower as the potential of the depolarization became more positive. 7. Lowering the temperature from 23 to 15 degrees C slowed the time-dependent current with an apparent Q10 of about 3.5 at V0. 8. Based on the experimental data, kinetic parameters were estimated for a model of Mg2+ block, which well simulated the inward-going rectification of the K+ current. 9. It is concluded that the instantaneous inward rectification on depolarization is due to the Mg2+ block at physiological [Mg2+]i.(ABSTRACT TRUNCATED AT 400 WORDS)
The effects of indeloxazine and piracetam, which reportedly prevent experimental impairments of memory and learning, on long-term potentiation (LTP) of the population spike in the mossy fiber-CA3 system were studied in vitro using the guinea pig hippocampal slices. Indeloxazine (10(-6) M) or piracetam (10(-4) M) significantly augmented the LTP and the effect of indeloxazine on the LTP was approximately 100 times as potent as that of piracetam.
Serum osmolalities and osmolar gap were determined in 43 normal healthy beagles (control group) and 40 dogs with dirofilarial hemoglobinuria (hemoglobinuria group). In the control group, the measured and calculated serum osmolality levels were in the means of 296 +/- 5 (SD) mOsm/kg and 293 +/- 6 mOsm/kg respectively, showing an osmolar gap less than 10 mOsm/kg. In the hemoglobinuria group, the measured serum osmolality ranged from 272 to 370 mOsm/kg. A considerable number of dogs had normal serum osmolalities in spite of severe intravascular hemolysis, suggesting that the changes in serum osmolality would not be the direct cause of intravascular hemolysis. The measured serum osmolality (331 +/- 28 mOsm/kg) was significantly higher in 11 dogs which died after a surgical removal heartworms than in 29 dogs which recovered after the removal (302 +/- 17 mOsm/kg). The calculated serum osmolality level was 296 +/- 16 mOsm/kg in 24 recovered cases, and 304 +/- 22 mOsm/kg in 10 fatal cases. The osmolar gap stayed in the normal ranges of 5.4 +/- 5.9 mOsm/kg in recovered cases, but it attained a higher level of 22.7 +/- 8.9 mOsm/kg in fatal cases, suggesting poor prognosis in cases with large osmolar gaps. There were significant positive correlations between the measured serum osmolality and osmolar gap, serum sodium, potassium, BUN, GOT, GPT, creatinine, bilirubin and plasma hemoglobin values, as well as between the osmolar gap and serum potassium, BUN, GOT, GPT, creatinine and bilirubin values. The plasma hemoglobin concentration fell markedly without significant change in serum osmolality 20 hr after the heartworm removal.
Some adverse reactions such as shock-like reaction and dirofilarial hemoglobinuria (caval syndrome) occasionally occurred in microfilaremic dogs following milbemycin D (Milbe) administration. This study was carried out to seek the prevention of these adverse reactions. In two groups containing 16 and 9 dogs respectively which were administered either chlorpheniramine maleate (1 mg/kg) or indomethacin (2.5 mg/kg) simultaneously with Milbe (1 mg/kg), the incidence of clinical signs such as the pale color of the visible mucous membranes, respiratory disorders, caval syndrome and shock-like reaction as well as changes in clinical parameters such as RBC and WBC counts, WBC profile and serum total protein, were almost equal to that observed in the group administered Milbe alone. In 41 dogs administered prednisolone (1 mg/kg) simultaneously with Milbe (1 mg/kg), no shock-like reaction was observed. Changes in clinical parameters were different from those in the group administered Milbe alone, whereas some clinical signs of adverse reactions, including caval syndrome, were observed. These results indicated that prednisolone was effective for prevention of the shock-like reaction in microfilaremic dogs induced by Milbe.
Rats with or without renal failure, produced by uranyl acetate, were subjected to water-immersion stress for 6 h. The severity of stress-induced gastric ulcers in the renal failure group was significantly higher than that in the control group. The intragastric pH did not significantly differ between the two groups. Transmucosal electrical potential difference, gastric mucosal blood flow, and gastric mucosal hexosamine content in the renal failure group were significantly lower than in the control group. These results suggest that decreases in defensive factors, rather than an increase in an aggressive factor, may be more closely involved in the development of acute gastric ulcers in rats with renal failure.
Many drugs are applied in local treatment for skin malignant tumors. These drugs are living-BCG, OK-432, MY-1, WPG, interferon preparation (alpha, beta and gamma), TNF, IL-2, peplomycin, bleomycin and others. Some of them already have completed clinical trials and others are under clinical observation. In local administration of these drugs, skin lesions (malignant melanoma, CTL-mainly mycosis fungoides, carcinoma in situ and others) show good improvement. The effects were more observed in the tumors with diameters of 1 cm or less and appeared 3 to 10 injections in most cases. As complications, there are fever, general fatigue, vomiting, anorexia, leucopenia and others. Among them, the fever was most observed immediately after injections without any more severe complications. It may be concluded that treatment by intratumoral administration is useful for skin malignant tumors.
The effects of NC-1300 on gastric acid and mucus glycoprotein secretion were investigated in pylorus-ligated (4 h) rats. NC-1300 (30 mg/kg, intraduodenally) significantly inhibited gastric acid concentration more than 90%. The agent did not affect the total mucus glycoprotein output in the gastric juice, but caused by about 1.5 times denser mucus glycoprotein secretion than that in the control group. The amount of mucus glycoprotein in the mucous gel layer increased by about 1.4 times with this agent. Thus, NC-1300 not only inhibits acid secretion but also promotes mucus secretion, and this may explain its ability to protect the stomach against necrotizing agents.
To apply a polymer as biomaterials in a variety of medical field, the evaluations of its adaptability to various kinds of cells are necessary. Therefore, the present paper describes not only the interaction between new polymer materials having phospholipid moiety (MPC) and human epithelial cell (Ca. 9.22) but also the change of platelet function in contact with the material for a prolonged period. In many examples few cells are able to adhere or grow on the surface of high water content gels, similar phenomena are observed in the case of high MPC content copolymers. This result indicates that MPC copolymer tends to offer insufficient liquid structure on which cells are able to adhere and grow. Since the suspended cells which did not adhere on these MPC copolymers survive for prolonged incubation period, it is evident that the MPC copolymer has good compatibility to the cells, and is inadequate for the cell attachment. As the polymers containing polar head group of phospholipids suppress attachment or adhesion of platelets and Ca. 9.22 cells, the polymers are potentially useful for the nonthrombogenic materials and the coating of biosensor which is inserted and retained in the human body.
The objective of this study was to prepare a new type water soluble bonding agent, methyl methacrylate (MMA)-p-styrene sulfonic acid copolymer (MS), and to investigate the effect of MS on bonding between resins and tooth substrates. MS is cross-linked with Ca2+ supplied by hydroxyapatite in a smeared layer on ground enamel and dentin and sticks to their surface. Samples were prepared by bonding an acrylic rod with MMA-TBB resin to ground enamel and dentin coated with an aqueous mixture of FeCl3 and 10 wt% MS. After immersed in water for 24 hrs, the tensile bond strength was measured. The bond strengths to both enamel and dentin were higher than 11 MPa and cohesive failure of cured MMA-TBB resin was observed in every case. This suggested that MS could adhere to tooth substrates with a new bonding mechanism different from the previously reported mechanism of the monomer interpenetration and polymerization.
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A retrospective study was made of the clinical features, especially oesophageal varices, of 93 patients with PBC. The 5 year survival rate of asymptomatic PBC patients was 88.7% and that of symptomatic PBC was 43.7%. The 5 year survival rate of the group with oesophageal varices was 44.0% and that of the group without varices was 68.8%. The 5 year survival rate of the patients with high-risk varices was 39.1% and of those without high-risk varices was 67.9%. Management of variceal bleeding in PBC patients was considered very difficult. In prognostic study, the patients with the prophylactic therapy were better than the patients with emergency or elective therapy. The antiM8 (a subtype of antimitochondrial antibody) positive patients had poor prognosis compared with antiM8 negative patients. Therefore, it was concluded from these data that some kind of treatment was necessary for patients with high-risk varices. In particular, it was considered necessary to monitor closely the patients whose serum alkaline phosphatase levels had remained high.
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Effects of prostaglandin E2 (PGE2) on murine B-cell activation induced by two distinct B-cell differentiation factors, B151-TRF1/IL-5 and B151-TRF2, were examined. A final differentiation of unprimed B cells into IgM-producing cells induced by B151-TRF2 was markedly inhibited by PGE2 at physiological concentrations (around 10(-8) M), whereas B151-TRF1/IL-5- induced antibody responses of unprimed as well as activated B cells were not affected by PGE2, even at 10(-6) M. B-cell responses induced by B151-TRF2-like factors from autoimmune-prone MRL/lpr mice were also inhibited by PGE2. Biphasic increases in intracellular cyclic AMP (cAMP) levels were induced by culturing B cells with 10(-6) or 10(-8) M PGE2: rapid increases within 8 min and delayed increases around 16 hr. The direct addition of dibutyryl cAMP to cultures of B cells resulted in marked inhibition of antibody responses when stimulated with B151-TRF2 but not with B151-TRF1/IL-5. The B151-TRF2-induced antibody responses were also inhibited by cAMP-elevating reagents such as forskolin, cholera toxin and theophylline. Furthermore, 2'.5'-dideoxyadenosine, which is an inhibitor of adenylate cyclase, prevented the PGE2-mediated cAMP accumulation in unprimed B cells as well as the PGE2-mediated inhibition of B151-TRF2-induced B-cell responses when added at the initiation of culture. These results suggest that PGE2 inhibits B151-TRF2-induced antibody responses through the activation of adenylate cyclase and subsequent accumulation of intracellular cAMP, whereas B151-TRF1/IL-5-responsive B cells are resistant to the inhibitory effect of PGE2 and cAMP.
Hemoglobinopathy was detected in a 72-year-old female with basal cell carcinoma of the genial region during high-performance liquid chromatography of hemolysate for the assay of HbA1c. Structural analysis demonstrated that this abnormal hemoglobin was identical to Hb Hope [beta 136(H14)Gly----Asp]. No clinical or hematological abnormality was observed. A study of the family revealed that a younger sister and two sons of the propositus had the same hemoglobin variant. This is the second observation of Hb Hope in a Japanese family.
The following factors were investigated in 43 cases of plantar malignant melanoma: maximum diameters of primary lesions, Clark's subtypes, clinical stages, UICC's stages, Clark's levels of invasion, Breslow's tumor thickness, and prognosis of patients. Relation of maximum diameter of primary lesions to various prognostic factors and prognosis of the patients was analysed. It was revealed that there were no statistically significant relationships between maximum diameters and other various factors. In our series, however, all patients with plantar malignant melanoma less than 14 mm in diameter are alive without metastasis. Judging from our previous and present studies, the following two points are the most important for improving the prognosis of patients with plantar malignant melanoma: 1) Catching all pigmented lesions on the sole that are more than 7 mm in diameter and examining them histologically, if they have no possibility of being congenital melanocytic nevus or black heel. 2) Treating plantar malignant melanomas adequately before they become 14 mm in maximum diameter.