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Biomedical subjects

Y Kuroiwa

Publications and source records attributed to Y Kuroiwa.

At least 19 recordsLinked to original sources
PubMed1992

Induction by bufalin of differentiation of human leukemia cells HL60, U937, and ML1 toward macrophage/monocyte-like cells and its potent synergistic effect on the differentiation of human leukemia cells in combination with other inducers.

We have recently demonstrated that bufalin is a new potent inducer of the differentiation of human myeloid leukemia cells. The present work was carried out to examine further the effect of bufalin on the growth and characteristics of human leukemia-derived cell lines U937, ML1, and HL60. At concentrations of 5-10 nM, bufalin decreased the growth of ML1 cells preferentially at the G2 phase and U937 cells at the S and G2 phases of the cell cycle. Bufalin, under these conditions, induced the differentiation of U937, ML1, and HL60 cells to monocyte/macrophage-like cells by measuring the expression of various differentiation markers, as assessed by morphology and histochemistry, and ability to phagocytose latex particles, to reduce nitroblue tetrazolium, and to develop Fc receptors. U937 and ML1 cells started to differentiate at 4 and 6 h, respectively, after treatment with 10 nM bufalin and showed maximum differentiation 72 h later. At present, a mechanism for the bufalin-mediated induction of the differentiation of these human leukemia cells remains to be determined. The combination of bufalin with all-trans retinoic acid, 1 alpha,25-dihydroxyvitamin D3, 4'-demethylepipodophyllotoxin ethylidene-beta-D-glucoside (VP16), or human gamma-interferon synergistically induced the differentiation of HL60 and U937 cells. A similar effect on ML1 cells was observed with the combination of bufalin with VP16 or human rTNF-alpha. These results suggest that bufalin in combination with VP16, all-trans retinoic acid, 1 alpha,25-dihydroxyvitamin D3, rTNF-alpha, or gamma-interferon may be very useful in the differentiation of human leukemia.

Antineoplastic Agents↗
PubMed1992

Induction of hepatic microsomal cytochrome P450 and drug-metabolizing enzymes by 4-benzylpyridine and its structurally related compounds in rats. Dose- and sex-related differential induction of cytochrome P450 species.

We examined the abilities of 4-, 3- and 2-benzylpyridine and 4-tert-butylpyridine to induce hepatic microsomal cytochrome P450 and drug-metabolizing enzymes in male and female rats in order to define the effects of pyridine-containing compounds on drug metabolism. 4-Benzylpyridine (0.4 mmol/kg, for 2 consecutive days) induced total cytochrome P450 to about three times that of the controls at 24 hr, and its inducing effect was sustained for 120 hr after the treatment in male and female rats. 4-Benzylpyridine was a more potent inducer of cytochrome P450 than 3- and 2-benzylpyridine, which induced the cytochrome to 71.4 and 43.9%, respectively, of that produced by the 4-substituted isomer. 4-tert-Butylpyridine also induced cytochrome P450. Immunoblot analysis revealed that a single treatment of male rats with 4-benzylpyridine at doses ranging from 0.05 to 0.80 mmol/kg induced cytochrome P450b/e and caused a maximum increase in the level of the isozyme at the 0.2 mmol/kg dose. 4-Benzylpyridine at doses from 0.40 to 0.80 mmol/kg also induced cytochrome P450c/d in male rats. In female rats, 4-benzylpyridine induced cytochrome P450b at doses ranging from 0.1 to 0.80 mmol/kg and produced a maximum increase in the level of this isozyme at 0.40 to 0.60 mmol/kg. Induction of cytochrome P450c/d by 4-benzylpyridine in female rats was observed at a dose of 0.20 mmol/kg, and the magnitude of the induction of the isozyme was increased in a dose-dependent manner. Both 3- and 2-benzylpyridine induced cytochrome P450b/e and/or c/d depending on the increase of total cytochrome P450 without changing the induction patterns of the isozymes. 4-tert-Butylpyridine induced cytochrome P450b at doses ranging from 0.20 to 0.60 mmol/kg and slightly induced P450c/d at doses ranging from 0.10 to 0.40 mmol/kg in male rats. These results and our previous report (Matsuura et al., Biochem Pharmacol 41: 1949-1956, 1991) clearly show that the pyridine compounds having lipophilic groups at the 4- or 3-position of the ring could be inducers of cytochrome P450. The present results also revealed that 4-benzylpyridine shows dose- and sex-related differences in the induction of cytochrome P450b/e and c/d in rats.

Aminopyrine N-Demethylase↗
PubMed1992

Stimulation of melanin synthesis of B16-F10 mouse melanoma cells by bufalin.

Bufalin, which is one of prominent components of Chinese toad venom, was found to decrease the rate of cell proliferation of mouse melanoma clone B16-F10 cells and a concomitant stimulation of expression of its melanotic phenotype. The effect of bufalin on melanogenesis included stimulation of tyrosinase activity and increase of cellular melanin content. These effects became apparent after 48 hr exposure to 10(-4) M bufalin and increased thereafter. Other cardiotonic steroids, such as cinobufagin and ouabain, at the concentration of 10(-4) M for 6 days, also showed the stimulatory effect on melanin synthesis of B16-F10 cells, but not digitoxigenin.

Animals↗
PubMed1992

Establishment of stable cell lines producing anti-Pseudomonas aeruginosa monoclonal antibodies and their protective effects for the infection in mice.

Human-human hybridomas producing monoclonal antibodies (MoAbs) specific for five major serotypes of Pseudomonas aeruginosa were developed by fusing P. aeruginosa primed and Epstein-Barr virus-transformed cells with human myeloma P109 cells using polyethyleneglycol. The MoAbs which were produced by the hybridomas were protective against lethal intraperitoneal (i.p.) challenge of P. aeruginosa (10 LD50) in mice. The 50% effective dose (ED50) values of MoAbs ranged from 0.5 to 10.2 micrograms/mouse and were 26 to 240 times more protective than a commercial human IgG preparation. MoAb administration to mice promoted bacterial clearance in peritoneal cavity, and prevented bacterial invasion into blood in the way of increasing both the number of bacteria trapped by a macrophage and the ratio of macrophages that trapped bacteria. MoAbs also showed protective effects against lethal infection of P. aeruginosa in the mice which were decreased in polymorphonuclear cells (PMN) by cyclophosphamide (CY). All MoAbs showed serotype-specific binding to the clinical isolates of P. aeruginosa as well as to the immunized strains. The hybridoma cell lines maintained their capacity to produce MoAb continuously for more than 12 months and produced 10 to 60 micrograms MoAbs per 10(6) cells in 24 hr. It is practicable to use these cell lines for large-scale production of anti-P. aeruginosa MoAbs and such MoAbs must be useful for the therapeutics of patients with P. aeruginosa infection.

Animals↗
PubMed1992

Dysphagia following various degrees of surgical resection for oral cancer.

Postoperative swallowing problems were investigated in 20 patients who had undergone various degrees of surgical resection for oral cancer. The swallowing problems were evaluated on the basis of type of food, degree of aspiration, and duration of postoperative nasogastric tube feeding. Two patients with tongue cancer who had had hemiglossectomy without reconstruction ate normal food without aspiration within a week after operation. Eight patients who had undergone two- to three-quarter glossectomy for tongue cancer ate gruel with no or occasional liquid aspiration. Among 4 patients who had had near-total or total glossectomy for tongue cancer, 3 ate thin gruel or liquid with occasional aspiration. The other could not eat orally because of consistent severe aspiration. One patient with mouth floor cancer underwent resection of the mouth floor in combination with hemiglossectomy and she ate gruel without aspiration. Among 5 patients with mouth floor cancer who had had surgical removal accompanied by near-total or total glossectomy, 3 ate gruel with no or occasional liquid aspiration, 1 ate thin gruel with no aspiration, and the other could not eat orally. A diagnosis of T4 lesions, extensive removal of the tongue base, removal of the geniohyoid and mylohyoid muscles, and removal of the lateral pharyngeal wall were significantly related to poor swallowing function.

Aged↗
PubMed1992

Selective effect of chronic lead ingestion on tyrosine hydroxylase activity in brain regions of rats.

Alterations of tyrosine hydroxylase activity in various regions of brain from rats postnatally exposed to lead were tested. Three groups of animals were prepared; (1) Rats exposed to lead at a low dose (0.05% lead acetate, PbAc); (2) Rats exposed to lead at a high dose (0.2% PbAc); (3) Age-matched normal control rats. At 2, 4, 6, and 8 weeks of age, weight of brain and body, and concentrations of lead in whole brain of animals in each group were measured. Activities of tyrosine hydroxylase and Na(+)-K+ ATPase were also measured at the same ages in 4 brain regions of each animal. Body weight gain was decreased after 6 weeks of age in rats exposed to lead at a high dose. Concentrations of lead in whole brain were increased from 0.37 to 0.83 (ng/mg wet tissue) in these animals. Exposure of rats to lead generally increased tyrosine hydroxylase activity and decreased Na(+)-K+ ATPase activity. However, changes of tyrosine hydroxylase activity were detected without concomitant changes of Na(+)-K+ ATPase activity in pons-medulla at 2 weeks of age and telencephalon at 6 weeks of age in rats exposed to lead at a low dose, and in midbrain at 4 and 6 weeks of age in rats exposed to lead at a high dose. These data imply that catecholaminergic nervous system in the brain regions described above could be selectively affected by lead.

Animals↗
PubMed1991

Bufalin as a potent inducer of differentiation of human myeloid leukemia cells.

Bufalin was found to be a potent inducer of differentiation in human erythroleukemia K562 cells by examination of various differentiation markers (as assessed by the morphology, histochemistry, and the abilities to phagocytose latex particles, to reduce nitro-blue tetrazolium and to develop Fc receptors). Bufalin, at a concentration as low as 10 nM, also produced a strong differentiation-inducing activity in three other human leukemia-derived cell lines (human promyelocytic HL60, monoblastic U937 and myeloblastic ML1). Treatment of K562 cells with other cardiotonic steroids, such as cinobufagin, ouabain and digitoxigenin, at the concentration of 10 nM for four days resulted in weak or no effect on the cells. These findings suggest that bufalin might have potentiality as a new agent in the differentiation therapy for human myelogenous leukemia.

Bufanolides↗
PubMed1991

Structure-activity relationships in the induction of hepatic microsomal cytochrome P450 by clotrimazole and its structurally related compounds in rats.

We investigated the structure-activity relationship in the induction of hepatic microsomal cytochrome P450 by clotrimazole and its structurally related compounds. For this purpose, we synthesized various compounds structurally analogous to clotrimazole and injected them into rats at a fixed dose of 0.2 mmol/kg. We found that the chlorine atom in clotrimazole was not necessary for the induction of cytochrome P450. The imidazole moiety of clotrimazole, however, was a very important structural component for the induction of cytochrome P450; triazole, but not pyrrole, could be substituted for this moiety. 1-Tritylimidazole, 1-diphenylmethylimidazole and 1-benzylimidazole were also found to be inducers of cytochrome P450, but, to a somewhat lesser extent, with a decreasing number of substituted phenyl groups. Thus, 1-benzylimidazole was a minimum structurally active unit for inducing cytochrome P450. In addition, 4-diphenylmethylpyridine and 4-benzylpyridine also induced cytochrome P450 to extents similar to those induced by the corresponding imidazole derivatives, but 4-benzylpiperidine lacked this effect. When the methylene unit of clotrimazole-related compounds was introduced by a hydroxy or amino group instead of imidazole, there was a less extensive increase in cytochrome P450 content. This inducing effect was lost completely by the lack of an imidazole moiety and imidazole itself. 1-Phenylethylimidazole and 1-benzylimidazole induced cytochrome P450 to a similar extent. All of these findings suggest that 1-substituted heteroaromatic compounds having two or more nitrogen atoms are likely to be required for inducing cytochrome P450. Immunoblot analysis revealed that clotrimazole and other various inducers found in this study increased cytochrome P450b/e content. These results could provide information on the effects of drugs and chemicals on cytochrome P450 induction.

Animals↗
PubMed1991

Comparative studies of the effects of stilbene compounds on hepatic ornithine decarboxylase and S-adenosylmethionine decarboxylase induction in rats.

Trans-Stilbene oxide (TSO, 2 mmol/kg, ip.) induced ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) to 60-fold and 5-fold of the controls, respectively, in the liver of rats. Parallel to ODC induction, there was a marked increase in putrescine content to 50-fold of the control levels. Cis-Stilbene oxide (CSO), a stereoisomer of TSO, also produced the induction of ODC and SAMDC and the increase in putrescine content. There was no difference in the ability to induce ODC and SAMDC between TSO and CSO with respect to the extents of induction and the time needed to reach maximal levels. Trans-Stilbene (TS), a mother compound of TSO, did not show such an effect on ODC, while cis-stilbene (CS) induced both ODC and SAMDC. Treatment with glutathione inhibited TSO- and CSO-mediated induction of ODC and SAMDC. These findings add new information concerning the abilities of TSO, CSO and CS on hepatic polyamine metabolism.

Acetylcysteine↗
PubMed1991

Development of monoclonal antibodies reactive with methamphetamine raised against a new antigen.

Monoclonal antibodies (McAbs) specific to methamphetamine (MA) were produced using p-amino MA coupled to bovine serum albumin (BSA) with glutaraldehyde (GA) as an immunogen and with conventional hybridoma techniques. Hybridoma clones secreting the McAbs were selected by an enzyme-linked immunosorbent assay (ELISA) system using both the above conjugate and BSA modified with GA as screening antigens. In the ELISA system were used avidin and biotinyl-alkaline phosphatase which converts nicotinamide adenine dinucleotide phosphate (NADP) into NAD. The final enzyme activity was determined using diformazan of nitroblue tetrazolium formed together with the NAD produced, alcohol dehydrogenase and phenazine methosulfate. The McAbs from 9 clones were characterized by a crossreactivity test using the ELISA. The McAbs recognized MA (100%), methoxyphenamine (8.0%), ephedrine (2.3%), but did not react with metylephedrine, amphetamine, OH-amphetamine, dimethylamphetamine, beta-phenylethylamine, norephedrine, phentermine and ranitidine. An inhibition curve for MA was obtained in the range of 0.75 to 50 ng.

Animals↗
PubMed1991

Effect of non-enzymatic glycosylation and heating on browning of human stratum corneum and nail.

The purpose of the present study was to examine the effect of non-enzymatic glycosylation and subsequent heating on the browning of the plantar stratum corneum and the finger-nail, and to elucidate the pathogenesis of the yellow skin and the yellow nail seen in diabetic subjects. We incubated stratum corneum and nail from non-diabetics in 0 (control), 10 (only nail), 20 (only nail), 100 and 250 mM glucose buffer at 37 degrees C for 5 days. These glycosylated samples were dialysed against distilled water for 96 h. Distilled water was changed every 24 h. Then samples were dried for 24 h. The extent of non-enzymatic glycosylation was measured by furosine content. Each 5 mg of sample was hydrolysed by 6 N HCl and processed for measurement of furosine by high-performance liquid chromatography. The rest of each sample was stored at 37, 42 (only nail), 47 and 52 degrees C for 14 days. Browning of the stratum corneum was assessed macroscopically, and that of the nail by spectrophotometry. Based on their spectrophotometric reflectances. Munsell's scores (H = hue score, V = lightness score, C = saturation score) and (H + C)/V were calculated for objective evaluation of browning. Incubation of the stratum corneum and nail with glucose buffer increased their non-enzymatic glycosylation (furosine) dose dependently. Macroscopically, the browning of the stratum corneum was enhanced in proportion to the glucose concentration and storage temperature. However, samples incubated in 10 and 20 mM glucose and stored at 42 degrees C did not show visible browning. Munsell's score of the nail samples treated by glycosylation and heating showed increased hue and saturation but reduced lightness. (H + C)/V values of these nail samples were significantly higher than those of the control. We could not detect any fluorescence with Wood light in the browned samples. The present in vitro study demonstrated that the browning of the stratum corneum and the nail depended on the extent of both non-enzymatic glycosylation and storage temperature. We suggested a hypothesis that the non-enzymatic glycosylation and the storage temperature of the stratum corneum and the nail might be a contributory factor in the development of yellow skin and yellow nail in diabetic patients.

Adult↗
PubMed1991

Characteristic changes of the GABAA receptor in the brain of phenobarbital-dependent and withdrawn rats.

The changes of the GABAA receptor in the brain of phenobarbital (PB)-dependent and -withdrawn rats were investigated using [3H]-muscimol (a potent agonist of GABAA receptor) as the ligand. The dissociation constant for a low affinity binding site (Kd2) of PB-dependent rats significantly increased without affecting the high affinity site (Kd1) and Bmax for both sites. A decrease of specific [3H]-muscimol binding was observed in the whole brain and the cerebellum of the PB-dependent rats, when examined at a fixed drug concentration of 2 nM. Moreover, the specific [3H]-muscimol binding in the withdrawn rats was remarkably lower than that of the dependent rats. These results suggest that the change of the GABAA receptor may be related to the development of PB-dependence and -withdrawal.

Animals↗
PubMed1991

[Electrophysiological studies of a case of startle disease].

A 53-year-old female with startle disease (major form) was reported. An abnormal startle response was the most prominent clinical feature. Physical examination revealed left lateral gaze palsy and left extensor plantar response. The caloric test evoked no responses bilaterally. Blood examinations including lysozomal enzymes and radiological examinations including MRI of the brain were all normal. A pathological startle reflex was elicited by the tap on the upper lip, causing the marked extension of the head with the elbow, hip, and knee joints slightly flexing. The earliest reflex activity in a surface-EMG study was recorded in the masseter muscle and the reflex then spread down the brain stem and the spinal cord. The duration of the discharge varied from 16 to 30 ms. The onset latencies of these responses from the tap were 11.2 ms, 12.7 ms, 14.5 ms, 25.7 ms, 38.5 ms, and 47.5 ms in the masseter, sternocleidomastoid, posterior-neck, biceps brachii, quadriceps femoris, and tibialis anterior muscle, respectively. An averaged electroencephalogram triggered by the taps showed no abnormal EEG activity preceding the pathological startle response, although a negative peak, which was thought as a normal early component of the trigeminal somatosensory evoked potentials, was followed by the reflex. High amplitude SEPs and long loop reflexes were observed following stimulation of the posterior tibial nerve but not of the median nerve. Blink reflexes and auditory evoked potentials were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiology↗
PubMed1990

Immunoassay for methamphetamine with a new antibody.

p- and o-Aminomethamphetamine were synthesized as haptens to be coupled with carrier protein at the benzene ring of methamphetamine. Immunogens were prepared by the glutaraldehyde method or the MBS (N-(m-maleimidobenzoyloxy)succinimide) type cross-linking reagent method. In particular, immunization with p-aminomethamphetamine-bovine serum albumin (BSA) conjugate prepared by the glutaraldehyde method gave an anti-methamphetamine antiserum having a low cross-reactivity with methylephedrine. With the antiserum, three kinds of immunoassays for methamphetamine were established. An enzyme immunoassay (EIA) and an enzyme-linked immunosorbent assay (ELISA) were developed with alkaline phosphatase (ALP) as a label enzyme. The amount of antibody bound ALP conjugate was determined by its activity in dephosphorylating p-nitrophenyl phosphate in EIA and nicotinamide adenine dinucleotide phosphate (NADP+) in ELISA. The range of methamphetamine measurable by ELISA was 0.025-0.5 ng/well and its sensitivity was superior to that of EIA (0.3-300 ng/tube). A latex agglutination inhibition reaction test (LAIRT) was also developed for the mass screening method of urine samples. The sensitivity of this method for methamphetamine was 0.1 micrograms/ml urine.

Alkaline Phosphatase↗
PubMed1990

Possible role of glutathione depletion in the induction of rate-limiting enzymes involved in heme degradation and polyamine biosynthesis in the liver of rats.

Ten compounds with a wide variety of structures, which decreased hepatic glutachione (GSH) content at an early time period after their administration, simultaneously increased hepatic heme oxygenase, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activities in rats. The compounds examined were four alpha, beta-unsaturated carbonyl compounds, two prototype substrates for GSH transferase(s), one epoxide, two isothiocyanates, and an indicator of hepatic function test. Time course studies with 1-chloro-2,4-dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzene (DCNB), which are prototype substrates for GSH transferases, showed that there was an inverse relationship between the early depletion of hepatic GSH content and induction of heme oxygenase, ODC and SAMDC together with a decrease in cytochrome P-450 content and an increase in putrescine content. Buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, also increased heme oxygenase and SAMDC activities, but not ODC, and it tended to enhance the induction of the enzymes evoked by diethyl maleate (DEM), phorone and CDNB with the sustained depletion of GSH content. In contrast, GSH treatment inhibited DEM-, phorone-, and CDNB-mediated induction of these enzymes and the early depletion of GSH content. N-Acetylcysteine failed to inhibit DEM- and phorone-mediated induction of these enzymes and the early depletion of GSH content, while it inhibited somewhat these changes produced by CDNB. The findings suggest that the early depletion of hepatic GSH content is prerequisite for and plays a role in the induction of heme oxygenase, ODC and SAMDC.

Adenosylmethionine Decarboxylase↗
PubMed1990

Laterality of cerebral controls on somatic and autonomic functions.

The mode of cerebral representation for each half of the body is various according to the functions that are represented; contralateral, ipsilateral and bilateral. We reviewed, and discussed the meaning of, such different patterns of cerebral representation for somatic and autonomic functions.

Autonomic Nervous System↗
PubMed1989

Autosomal recessive motor and sensory neuropathy with excessive myelin outfolding.

Two Japanese persons with consanguinous parents had a motor and sensory neuropathy of the hypertrophic type with excessive myelin outfolding in the myelinated fibers. A morphometric analysis of the biopsied sural nerve was made. Excessive myelin outfolding, segmental demyelination, and remyelination and decrease in the density of both large and small myelinated fibers were evident. Using linear regression, myelin spiral length was shorter relative to axonal area. These patients may have a new variant of hereditary motor sensory neuropathy.

Adolescent↗