Search PubMed⌕ Search

Biomedical subjects

M Isaka

Publications and source records attributed to M Isaka.

At least 19 recordsLinked to original sources
PubMed1999

Intranasal or subcutaneous co-administration of recombinant cholera toxin B subunit stimulates only a slight or no level of the specific IgE response in mice to tetanus toxoid.

Whether recombinant cholera toxin B subunit (rCTB) co-administered intranasally or subcutaneously with aluminium-non-adsorbed tetanus toxoid (nTT) can induce the production of tetanus toxoid (TT)-specific IgE antibodies in mice was investigated compared with aluminium-adsorbed tetanus toxoid (aTT) administered intranasally or subcutaneously. Mice immunized intranasally or subcutaneously with nTT together with rCTB showed a high level of TT-specific serum IgG antibody response and no or a slight level of TT-specific serum IgE antibody response. On the other hand, in mice vaccinated intranasally or subcutaneously with aTT alone, higher levels of TT-specific IgG and IgE antibodies were induced in comparison with intranasal or subcutaneous inoculation of nTT together with rCTB. These results suggest that intranasal or subcutaneous co-administration of rCTB with nTT is better than intranasal or subcutaneous administration of aTT to avoid IgE-mediated allergic reactions.

Adjuvants, Immunologic↗
PubMed1999

Cyclopropenone-containing cysteine proteinase inhibitors. Synthesis and enzyme inhibitory activities.

By focusing on the amphiphilic properties of cyclopropenone (e.g. a good electrophile and a precursor for a stable 2pi-aromatic hydroxycyclopropenium cation), a new class of cysteine proteinase inhibitors containing a cyclopropenone moiety was designed. For the purpose of the present research, we needed to devise a new method to introduce a peptide-related moiety as a substituent on the cyclopropenone residue. We investigated the reaction of metalated cyclopropenone acetal derivatives (2, R2 = metal) with N-protected alpha-aminoaldehydes 4 to obtain the adduct 5, and succeeded in the preparation of highly potentiated cysteine proteinase inhibitors 8 after several steps transformations. They showed strong inhibitory activities only to cysteine proteinases such as calpain, papain, cathepsin B, and cathepsin L and not to serine (e.g. thrombin and cathepsin G) and aspartic proteinases (e.g. cathepsin D). Kinetic studies indicated that they are competitive inhibitors, and by the examinations of their inhibitory mechanism it became clear that they are reversible inhibitors.

Calpain↗
PubMed1998

Alpha1-adrenoceptor subtypes and two receptor systems in vascular tissues.

The subtypes of alpha1-adrenoceptor are coexpressed in many tissues. We examined the relationship between coexpressed alpha1-adrenoceptor subtypes and their functions in blood vessels. Rat and rabbit aortas coexpressed three subtypes (alpha1A, alpha1B, alpha1D) and four subtypes (alpha1A, alpha1B, alpha1D, alpha1L), respectively. In rat aorta however, noradrenaline-induced contraction was mediated predominantly through the alpha1D subtype, and oxymetazoline produced alpha1B-mediated contraction. In rabbit aorta, concentration-response curves for noradrenaline were composed of two components (alpha1B and alpha1L-mediated), while oxymetazoline produced alpha1L-mediated contraction. Therefore, the inhibitory actions of some antagonists varied markedly among tissues and agonists. These results demonstrate diversity of the two receptor systems and suggest that the heterogeneity of physiological responses reflects the differences in functional subtypes among tissues and in their sensitivities to agonists and antagonists.

Adrenergic alpha-Agonists↗
PubMed1998

Systemic and mucosal immune responses of mice to aluminium-adsorbed or aluminium-non-adsorbed tetanus toxoid administered intranasally with recombinant cholera toxin B subunit.

For the purpose of changing the immunization procedure of tetanus toxoid from intramuscular or subcutaneous injection, which has been in practice for a long time, to intranasal administration, we examined systemic and mucosal immune responses of mice to aluminium-adsorbed tetanus toxoid (aTT) and aluminium-non-adsorbed tetanus toxoid (nTT) inoculated intranasally with recombinant cholera toxin B subunit (rCTB). Intranasal immunization with aTT induced, at a concentration of 0.5 Lf, high levels of TT-specific serum IgG antibody titres and moderate levels of TT-specific serum IgA antibody titres in the presence and absence of rCTB. Induction of high or moderate levels of mucosal TT-specific IgA antibody responses was observed with and without rCTB in the lung, the nasal cavity, the small and large intestines and the vagina. Generally speaking, the co-administration of aTT and rCTB showed higher mucosal TT-specific IgA antibody titres when compared with the administration of aTT alone. In case of intranasal administration of nTT, the dose of 5 Lf was necessary and stimulated, only in the presence of rCTB (10 micrograms), high levels of tetanus toxoid (TT)-specific serum IgG antibody responses in all mice examined and moderate or slight levels of TT-specific IgA antibody responses in the nasal, pulmonary and small and large intestinal lavages of a few mice. All mice intranasally immunized with aTT alone or nTT and rCTB escaped onset of tetanus. This is the first report concerned with the mucosal adjuvant activity of an aluminium compound. Judging from these results, intranasal administration of aTT with and without rCTB or nTT with rCTB appears to be a very useful means for a vaccination against tetanus with respect to ease, safety, certainty, low cost and no need for an injection needle.

Administration, Intranasal↗
PubMed1995

[Acute lymphoblastic leukemia accompanied by severe hypercalcemia; successful treatment with bisphosphonate].

A 62-year-old woman was admitted to the hospital because of bone pain. Laboratory data showed blasts in the peripheral blood, hypercalcemia (corrected calcium 15.1 mg/dl) and an increased level of parathyroid hormone related-protein (PTHrP). Bone marrow aspiration revealed increased lymphoblasts (96.5%), indicating acute lymphoblastic leukemia (ALL, L1). Subsequent radiological examination disclosed bone infiltration of ALL. Although the hypercalcemia was successfully treated with bisphosphonate, the PTHrP level remained high. After chemotherapy, the blasts in the peripheral blood disappeared and the PTHrP level normalized. We hypothesize that in the present case the production of PTHrP by lymphoblasts resulted in the hypercalcemic state. Although ALL is rarely accompanied by hypercalcemia, this case might help us to understand the relationship between ALL and hypercalcemia.

Diphosphonates↗
PubMed1995

[Parathyroid selective venous sampling].

It is important to localize the site of abnormal parathyroid glands in treatment of primary hyperparathyroidism. Selective venous sampling with parathyroid hormone assay is one of the methods for localization of adenoma or hyperplasia in primary hyperparathyroidism. Since Reitz first described it in 1969, it has been improved during the last two decades and there is a high sensitivity (70-80%). Especially in those cases, localization is unknown in imaging methods, the first operation fails or the patients has previously been explored in the neck, venous sampling becomes a very useful method. How to perform, indication, performance, strengths and weakness of selective venous sampling is described here.

Blood Specimen Collection↗
PubMed1994

Transient induction of fatty acid synthase in rat liver after removal of a peroxisome proliferator.

Removal of a peroxisome proliferator from the diet triggered the degradation of peroxisomes and induced the transient expression of a 220 kDa soluble protein in rat liver. The 220 kDa protein was purified by conventional methods and analyzed by amino acid sequencing. A total of 99 amino acid residues in 4 lysylendopeptidase-digested peptides completely matched those in rat fatty acid synthase. The transient induction of fatty acid synthase mRNA during peroxisome degradation was confirmed by Northern blotting.

Amino Acid Sequence↗
PubMed1993

Hemodynamic effects of lipo-PGE1 on peripheral artery in patients with diabetic neuropathy: evaluated by two-dimensional color Doppler echography.

Twenty non-insulin-dependent diabetic patients were studied to evaluate the hemodynamic effects of lipo-PGE1 (prostaglandin E1 incorporated in lipid microspheres). Improvement of diabetic neuropathy was assessed on the basis of subjective symptoms such as pain, coldness, numbness and dysethesia (subjective) after intravenous administration of lipo-PGE1. After lipo-PGE1 treatment, the subjective symptoms were markedly improved. Hemodynamic effects of this drug on the dorsalis pedis artery were examined using new real-time two-dimensional color Doppler echography. After administration of lipo-PGE1, the cross-sectional area of the dorsalis pedis artery significantly increased from 2.6 +/- 0.2 mm2 to 3.5 +/- 0.2 mm2 (P < 0.01). Moreover, the blood flow index significantly increased from 40 +/- 7 to 61 +/- 11 (P < 0.05). The results of this study suggest that lipo-PGE1 may serve as a useful drug in improving diabetic neuropathy.

Adult↗
PubMed1992

High glucose and hyperosmolarity increase platelet-derived growth factor mRNA levels in cultured human vascular endothelial cells.

We investigated the effects of high glucose and hyperosmolality on platelet-derived growth factor (PDGF) production and PDGF-B chain mRNA levels in cultured human umbilical vein endothelial cells. Under an excess of ambient glucose (13.8 and 27.5mM) and a hyperosmolar condition (22.0mOsm/L with mannitol), PDGF concentrations in the culture medium were both significantly increased (10.3 +/- 6.0%, 36.2 +/- 7.2%, 48.5 +/- 9.0% increase respectively compared with 5.5mM glucose). Parallel to protein secretion levels, PDGF-B chain mRNA levels showed a significant increase (57.7%, 103.7%, 210.8% increase), while no change of beta-actin mRNA levels was observed. Thus, elevated PDGF released from endothelium by high glucose may play an important role in the pathogenesis of diabetic angiopathy.

Blotting, Northern↗
PubMed1992

Rat cellular mutants for expression of mRNA from the long terminal repeat of murine retrovirus.

Previously we isolated revertants from a rat cell line transformed by recombinant murine retrovirus containing the v-src gene. These mutant cell lines, R78 and R107, showed low src-kinase activity, but retained wild-type transforming retrovirus, suggesting that a cellular gene involved in viral gene expression was mutated. Southern and Northern hybridization analyses showed that the expression of viral mRNAs from the integrated proviral DNA was reduced in these mutant cells. DNA transfection experiments with various transforming genes and promoters revealed that the mutant cell lines were resistant to transformation by transforming genes expressed under the long terminal repeat (LTR) of Moloney murine leukemia virus (Mo-MuLV). In contrast, these cell lines could be efficiently transformed by the same transforming genes with human metallothionein promoter, polyomavirus promoter-enhancer, and c-H-ras promoter. Transient expression assays using plasmids containing the CAT gene under the LTR of Mo-MuLV also showed that CAT activity expressed under the LTR in these mutant cells was lower than that in the parental cell line, No. 7. These results suggest that cellular mutations of R78 and R107 cells affect specific transcription from the LTR of Mo-MuLV. Studies using various constructs of the LTR CAT indicated that the region responsible for the repression was located in a fragment (-328 to -150) of the LTR containing the 72-bp repeat enhancer. Somatic cell hybridization experiments showed that the mutant phenotype of these mutant cell lines is dominant to that of the parental cell line.

Animals↗
PubMed1992

Synthesis and biological activities of cyclopropenone antibiotic penitricin and congeners.

A number of derivatives of the cyclopropenone antibiotic penitricin have been synthesized by the reaction of metalated cyclopropenone acetals with electrophiles. Studies on the antimicrobial structure-activity relationships indicated that the penitricin skeleton, hydroxymethylcyclopropenone, is indispensable for antimicrobial activity. These compounds were also found to display cytotoxic activity.

Bacteria↗
PubMed1991

Simple system for isolation of cellular and viral mutants for transformation by retrovirus.

To investigate the cellular mechanism of transformation by retroviruses, we established a system for isolation of cellular and viral mutants for transformation of a rat cell line. Mutagenized untransformed cells of this line were infected with recombinant murine retrovirus containing the src gene of Rous sarcoma virus and the selective marker gene, neo. After reaching confluence, cells transformed by the src gene tend to overgrow and die. Utilizing this property of src transformed rat cells and the selective marker gene, we could easily select untransformed cell clones containing the retrovirus genome. Expression of the src gene product in the flat clones selected was examined by in vitro assay of src kinase activity. To determine whether the mutations of these flat clones were viral or cellular, the susceptibilities of the clones to transformation were examined after superinfection with the wild-type virus and also characterized the retroviruses recovered from these clones. With this system, two novel clones were isolated. One had a defect in viral information affecting the transformed phenotype, but still retained src kinase activity like fully transformed cells. The other showed low src kinase activity but retained wild-type transforming virus, suggesting that a cellular gene involved in viral gene expression was mutated.

Animals↗
PubMed1989

Increased sympathoadrenomedullary activity and left ventricular hypertrophy in young patients with borderline hypertension.

Echocardiographic dimensions and endocrinological examination were performed in 71 young patients with borderline hypertension (BHT) and 31 age-matched normotensive subjects (NT). Patients with BHT had significantly higher relative wall thickness (RWT) and left ventricular mass index than NT, although all BHT patients showed no asymmetric increase in the ratio of septal to posterior wall thickness. Moreover, these BHT patients demonstrated an increased cardiac output and an augmented mean circumferential fiber shortening rate (mean Vcf), suggesting left ventricular hyperfunction. Overall, there was a positive correlation between RWT and mean Vcf in BHT patients (r = 0.700, P less than 0.001), although there was no significant relationship between RWT and blood pressure. Furthermore, these BHT patients had higher plasma epinephrine (PE) and plasma renin activity compared to NT, suggesting the increased sympathoadrenomedullary activity in BHT. These BHT patients were divided into two groups with regards to PE levels; namely a high PE group (PE greater than or equal to 46 pg/ml) and a normal PE group (PE less than 46 pg/ml). The high PE group had a significantly higher mean Vcf and RWT than the normal PE group. These findings suggest that in young BHT patients left ventricular hypertrophy could be related to abnormalities of the sympathoadrenomedullary systems.

Adolescent↗