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Biomedical subjects

Y Kuroiwa

Publications and source records attributed to Y Kuroiwa.

At least 19 recordsLinked to original sources

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

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

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

De- and remyelination and onion bulb in cerebrotendinous xanthomatosis.

In a case of cerebrotendinous xanthomatosis (CTX), confirmed biochemically and histologically quantitative histological studies of the biopsies sural nerve revealed significantly higher incidence of de- and remyelination and onion bulb than in controls. The density of total myelinated fibers fell within the range of controls, although the density of large myelinated fibers seemed to be slightly decreased. It was suggested that the preferential involvement of the myelin sheath and Schwann cell may exist in CTX.

Adult

Oculomotor abnormalities in Parkinson's disease.

Ocular movement was studied in 19 patients with Parkinson's disease and in ten normal controls. Common abnormalities included "hypometric saccade" on the eye-tracking test and on command, "saccadic pursuit," and convergence paresis. Reaction time was longer in patients with Parkinson's disease than in controls for horizontal saccadic gaze, finger movements, and body movements. Maximal saccadic velocity of horizontal gaze was slower in patients with Parkinson's disease than in controls. Slowing of the horizontal saccadic movement correlated significantly with an increased reaction time of finger and body movements. Correlation of decreased saccadic velocity with increased reaction time of finger movement was found for the finger ipsilateral to the direction of horizontal gaze, but not for the contralateral finger. It is postulated from these facts that bradykinesia also exists in eye movements in Parkinson's disease.

Aged

Transmission of chronic spongiform encephalopathy with kuru plaques from humans to small rodents.

An unusual case of spongiform encephalopathy was transmitted directly from a human to rats and mice. After serial passages, incubation periods were shortened to about six months in rats and four months in mice. Clinical symptoms were similar in rats and mice, including ruffled fur, arched back, bradykinesia, and hind limb paralysis. Pathologically, a spongy state, proliferation of astrocytes, and neuronal changes were observed. Electron microscopic observation of the parietal cortex of rats and mice disclosed many membrane-bound vacuoles in the neuropil, predominantly in dendrites. In the pons of mice, intramyelinic vacuoles and accumulation of extracellular fluid were prominent. The clinicopathological symptoms of the affected animals resembled those in other experimental spongiform encephalopathies, especially scrapie.

Animals

Adult type mucolipidosis with beta-galactosidase and sialidase deficiency. Histological and biochemical studies.

A case of adult type mucolipidosis with beta-galactosidase and sialidase deficiency is described. This patient, a woman aged 20, had mental retardation, macular cherry-red spots, corneal clouding, gargoyle-like face, cerebellar ataxia, myoclonus and convulsions beginning at the age of 14. Bony deformities, vacuoles in the peripheral lymphocyte and foamy cells in the bone marrow were also noted. Biopsy study of the sural nerve and vermiform appendix disclosed many vacuoles in almost every kind of cells, although the accumulated substance in these vacuoles could not be characterized histochemically or ultrastructurally. Deficient leukocyte beta-galactosidase and sialidase were confirmed. There was increased urinary sialoglycopeptide and increased siliac acid and hexosamine in the glycoprotein of lymphocytes. Leukocytes sialidase activites of the parents were 30 to 50% of the control values. These results suggest a genetic defect of sialidase.

Adult

Pigmentary degeneration of the retina in heredodegenerative neurological diseases.

Frequency of pigmentary degeneration of the retina (PDR) among patients with degenerative and heredodegenerative neurological diseases (HDNDs) was estimated based on the hospital statistics. PDR was detected in 3% of 176 inpatients with HDNDs by careful ophthalmologic examination. On the other hand, out of 30 consecutive cases of PDR seen in our Department of Neurology, 15 patients were associated with some form of HDNDs. Atypical PDR were more frequently associated with HDNDs than typical PDR. Among neurological manifestations in those 15 cases of PDR associated with HDNDs, mental deficiency, hearing disturbance, spasticity, progressive ophthalmoplegia and ataxia were most frequently encountered. Four cases with unusual symptomatology were presented. Clinical analysis of cases of PDR associated with HDNDs in the present series as well as in the relevant literature revealed an extreme variety of clinical manifestations and underlying metabolic disorders, suggesting a possible participation of multiple factors in the pathogenesis of PDR. Importance of careful ophthalmologic examination in HDNDs was stressed from the prognostic point of view.

Adolescent

Rigid spine syndrome.

A patient is described with distinctive clinical features including childhood onset of non-progressive muscle weakness, limitation of flexion of the neck and spine, scoliosis, and joint contracture. Muscle biopsy and electromyography showed findings suggestive of a myopathic disorder. The combination of these distinctive clinical features is termed the rigid spine syndrome. Only six cases have been reported in the literature to date.

Adolescent

Lymphocyte function in myasthenia gravis.

Mitogen-induced blastoid transformation of peripheral blood lymphocytes from patients with myasthenia gravis was studied using a microplate culture technique and evaluated with 3H-thymidine incorporation. It was found that both phytohaemagglutinin and pokeweed mitogen responses decreased significantly in patients with myasthenia gravis. In myasthenic crisis, indices of stimulation by phytohaemagglutination became very low. The autologous plasma neither inhibited nor facilitated mitogenic responses of lymphocytes. The decreased mitogen responsiveness of lymphocytes suggests that part of the T lymphocyte function is subnormal in myasthenia.

Adult

Fabry disease: cellular expression of enzyme deficiency in nerve xenografts.

Human sural nerve fascicles from a patient with Fabry disease were transplanted into nude-mouse sciatic nerves to determine whether transplanted perineurial cells and smooth-muscle cells of an epineurial artery would express the genetic abnormality of the disease. Four months after grafting, both perineurial cells and smooth-muscle cells contained the cytoplasmic lamellated inclusion bodies characteristic of Fabry disease. This provided evidence of human perineurial cells and smooth-muscle cells in the regenerated xenografts.

Adult

Erythrocyte ATP in Duchenne dystrophy: effects of ouabain and propranolol.

The ATP and lactate contents of erythrocytes from patients with Duchenne muscular dystrophy (DMD) were measured before and after incubation with or without glucose plus either ouabain or propranolol. Samples from patients and controls were obtained at almost the same time on the same day and processed simultaneously. The erythrocyte ATP content differed in adults and children, but there was no difference between DMD patients and age-matched controls. Ouabain suppressed, and propranolol enhanced, the changes of ATP and lactate, to the same extent in patients and in controls. We found no gross abnormalities in generation and utilization of ATP in erythrocytes in DMD, and the response to ouabain or propranolol appeared normal.

Adenosine Triphosphatases

Spinal cord injury as a complication of an acupuncture.

Recently, acupuncture has been widely performed for the treatment of many different diseases. We studied a patient with migraine who had been treated by "okibari," an acupunctural procedure. About 20 needles were inserted permanently in the subcutaneous tissues of his neck and occipital scalp. About 6 months later he hit the back of his neck, and soon after this accident cervical myelopathy occurred. There have been no similar reports.

Acupuncture Therapy