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Biomedical subjects

Y Takeuchi

Publications and source records attributed to Y Takeuchi.

At least 37 records · Page 2Linked to original sources

Retroviral pseudotypes produced by rescue of a Moloney murine leukemia virus vector by C-type, but not D-type, retroviruses.

Human HOS cells containing a Moloney murine leukemia virus (Mo-MLV) recombinant genome were infected by a panel of retroviruses. The C-type viruses simian sarcoma associated virus, feline leukemia virus subgroup B, and the feline endogenous virus RD114 were able to form pseudotypes with the Mo-MLV genome, which transferred a selectable marker gene to target cells; however, Human T cell leukemia virus-1 and the D-type viruses Mason-Pfizer monkey virus and simian retrovirus-1 failed to rescue the Mo-MLV vector. Further characterization of the RD114 pseudotype demonstrated that it retained the receptor specificity of RD114 and will therefore prove useful in receptor characterization.

Animals

Perforin is expressed in CTL populations generated in vivo.

Immunization of C57BL/6 mice with syngeneic tumor cells, MBL-2, resulted in the generation of antitumor effector cells in vivo. The immunized C57BL/6 mice permanently rejected viable MBL-2 lymphoma cells, but not B16 melanoma cells. Cytotoxic T cells obtained from MBL-2-immunized mouse peritoneal cells (PEC) showed specific cytotoxicity against MBL-2, but not to YAC-1, RDM-4 and Meth A cells. By sorting with FACStar, the specific CTL were characterized as TCR alpha beta+ CD8+ T cells. Moreover, the cytoplasm of in vivo-induced CTL was stained with a monoclonal antibody against perforin. The localization of perforin in cytoplasmic granules of CTL was demonstrated by electron microscope analysis. This experiment presented the first evidence that in vivo-induced CD8+ CTL against syngeneic tumor cells expressed significant amounts of perforin.

Animals

The superior cervical ganglion: origin of sympathetic fibers in the facial and hypoglossal nerves in the cat.

Location of superior cervical ganglion (SCG) neurons, sending axons into the facial and hypoglossal nerves, was investigated in the cat by means of retrograde axonal transport of horseradish peroxidase (HRP). After wheat germ agglutinin conjugated HRP (WGA-HRP) was injected into these nerves, many retrogradely labeled neurons were found widely in the ipsilateral SCG, particularly around the caudal half of the SCG. These neurons were round or oval in shape and 70-80% of these were medium in size. In fluorescent experiments, fast blue (FB) was used in combination with diamidino yellow (DY). After injections of FB into the facial nerve and DY into the hypoglossal nerve, a few FB-DY double-labeled neurons occurred in the SCG ipsilaterally.

Adrenergic Fibers

Neuroleptic malignant syndrome-like state in a patient with Down syndrome and basal ganglia calcification.

We report a case of rhabdomyolysis in a 13-year-old Down syndrome patient with progressive quadriplegia, choreoathetosis and dystonia. Cranial CT demonstrated bilateral basal ganglia calcification. He experienced the sudden onset of high fever, cloudiness of consciousness, muscle rigidity and severe opisthotonus. The diagnosis was made on the basis of the marked increases in serum creatine kinase and myoglobin. There was remarkable elevation of 5-hydroxyindoleacetic acid, homovanillic acid and methoxy-hydroxyphenyl glycol in the cerebrospinal fluid during hyperpyrexia. This case exhibited almost all the diagnostic criteria of the neuroleptic malignant syndrome. It was suggested that abnormalities of monoamines in the central nervous system may be related to the pathologic etiology of this state and rhabdomyolysis.

Adolescent

Impact of influenza virus infection as a cause of pediatric hospitalization.

From winter 1989 to spring 1990, a severe epidemic caused by influenza A (H3N2) and B viruses developed in Japan. During the epidemic (December 1989 to February 1990), 244 children were admitted to the pediatric ward of Nippon Kokan Hospital: 53 (21.7%) were hospitalized with influenza virus infection, 22 (9.0%) with rotavirus gastroenteritis, and 17 (7.0%) with respiratory syncytial virus infection. Among those with influenza, 24 had type A and 29 had type B. Most were young healthy children without underlying illnesses (mean age, 4.8 +/- 3.4 years). The impact of the influenza epidemic on pediatric hospitalization is probably much greater than generally thought when a severe epidemic occurs.

Adolescent

In utero treatment with monoclonal antibody to IL-2 receptor beta-chain completely abrogates development of Thy-1+ dendritic epidermal cells.

Interleukin-2 (IL-2), a crucial growth factor for mature T lymphocytes, is produced in fetal thymus under developmental control, although its biological significance remains unclear. We found that the two distinct subunits of the IL-2 receptor, i.e. the alpha-chain (IL-2R alpha) and the beta-chain (IL-2R beta), were expressed in an almost mutually exclusive fashion throughout fetal thymus ontogeny, and that the blockade of IL-2R beta, a signal transducing component of IL-2R, by administering a neutralizing mAb to IL-2R beta resulted in the complete and selective disappearance of Thy-1+ skin dendritic epidermal cells. Development of any other T cell subsets was uncompromised. This indicates that IL-2 plays a crucial role in the development of fetal V gamma 5+ cells and their descendants.

Animals

Inhibition of heat inactivation of reverse transcriptase of human immunodeficiency virus type 1 by seropositive sera.

The reverse transcriptase (RT) activity of a lysate of human immunodeficiency virus type 1 (HIV) was almost completely inactivated by incubation at 56 degrees C for 20-30 min. The heat-inactivation of RT in the virus lysate or purified RT was partially inhibited in the presence of some human sera or plasma containing antibodies against HIV. The IgG fraction purified from the seropositive sera was responsible for stabilization of RT upon heat inactivation. This is a new assay system for detection of antibodies against RT.

Antigen-Antibody Reactions

Spinal arachnoid cyst in a newborn infant.

A male infant was born with asphyxia following a prolonged breech delivery at 39 weeks of gestation. He had a chylohemothorax from birth. Soon after birth he exhibited flaccid paraplegia with an absence of deep tendon reflexes in the lower extremities. At 17 days of age, magnetic resonance imaging (MRI) disclosed a hypodense area in the thoracic cord between C7 and Th4 in T1-weighted images, and spinal sonography revealed an echo-free space compressing the spinal cord in the same region observed with MRI. A spinal cyst was removed surgically at 24 days of age. The cyst was confirmed by pathology to be a true arachnoid cyst between C7 and Th4. The cause of this cyst may have been a spinal cord injury during the perinatal period.

Arachnoid Cysts

Epidemiology of neonatal chronic lung disease in Japan.

A nationwide survey on the epidemiology of chronic lung disease (CLD) of the newborn was conducted. Questionnaires were sent to 391 level II and III neonatal centers in Japan and the registration of infants born in 1990 with chronic lung disease was requested. CLD was defined as an oxygen requirement greater than that obtainable in room air at 28 days after birth, with symptoms of persistent respiratory distress and a hazy or emphysematous and fibrous appearance on chest X-ray. A total of 301 neonatal centers (77.0%) responded and 50,290 infants at these centers were registered. Of these, 97% survived the first month and 1,135 of 48,762 neonatal survivors developed CLD. The mortality of infants with CLD was 6.2%. Survival rates at 28 days of age increased consistently with birthweight. Survival at 28 days of age in infants below 1,000 g at birth was 73.7%, but the rate was 93.9% in infants weighing 1,000-1,499 g. The incidence of CLD was inversely proportional to birthweight. Approximately one quarter of neonatal survivors with a birthweight below 1,500 g and approximately half of extremely small infants ( < 1,000 g) developed CLD. The analysis of CLD infants showed that 28.2% of them had a history of respiratory distress syndrome (RDS) and a typical fibrous appearance on chest X-ray (Type I), while 29.3% also had a history of RDS but had an atypical X-ray appearance (Type II).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease

Feline leukemia virus subgroup B uses the same cell surface receptor as gibbon ape leukemia virus.

Pseudotypes of gibbon ape leukemia virus/simian sarcoma-associated virus (GALV/SSAV) and feline leukemia virus subgroup B (FeLV-B) have been constructed by rescuing a Moloney murine leukemia virus vector genome with wild-type GALV/SSAV or FeLV-B. The resulting recombinant viruses utilized core and envelope proteins from the wild-type virus and conferred resistance to growth in L-histidinol upon infected cells by virtue of the HisD gene encoded by the vector genome. They displayed the host range specificity of the rescuing viruses and could be neutralized by virus-specific antisera. Receptor cross-interference was observed when the GALV/SSAV or FeLV-B pseudotypes were used to superinfect cells productively infected with either GALV/SSAV or FeLV-B. Although murine cells are resistant to FeLV-B infection, murine cells expressing the human gene for the GALV/SSAV receptor became susceptible to FeLV-B infection. Therefore GALV/SSAV and FeLV-B utilize the same cell surface receptor.

3T3 Cells

Dose dependent effects of chronic exposure to toluene on neuronal and glial cell marker proteins in the central nervous system of rats.

The dose dependent effects of chronic exposure to toluene on the neuronal marker proteins (gamma-enolase, calbindin-D28k) and glial cell marker proteins (alpha-enolase, creatine kinase-B, and beta-S100 protein) were investigated in the central nervous system (CNS) of rats. Three groups of animals were exposed to 100 ppm, 300 ppm, or 1000 ppm toluene vapour eight hours a day, six days a week for 16 weeks. The contents of the marker substances were determined with enzyme immunoassays. A significant increase in the three glial cell marker proteins was noted in the cerebellum after exposure to 100 ppm toluene; a more pronounced increase occurred at the higher toluene concentrations. beta-S100 protein also exhibited a dose dependent increase in the brainstem and spinal cord. On the other hand, the two neuronal cell markers did not show a quantitative decrease in the CNS. This means that the development of gliosis, rather than neurone death, is induced by chronic exposure to toluene. The significant biochemical changes induced around the threshold limit value and the concentration dependent alterations suggest that these nerve specific marker proteins may be used to evaluate solvent related damage to the CNS.

Animals

Effects of neonatal asphyxia on the serotonin neuron system in the developing brain studied by immunohistochemistry.

The effects of neonatal asphyxia on the serotonin neuron system were examined using the immunoperoxidase method. Male mice, 2 days of age, were exposed to total asphyxia (100% CO2) for 30 min. Mice that spontaneously survived were perfused transcardially with a fixative at 15, 30 and 60 days of age. Quantitative immunohistochemical analysis at 60 days of age demonstrated a significant decrease in the numbers of serotonin-immunoreactive cell bodies in the nucleus raphe dorsalis, the nucleus raphe pontis, the subpyramidal region, the total raphe system and the whole brain, while no significant reduction in the number of serotonin-immunoreactive cell bodies was observed in the caudal raphe system. Presumably degenerative changes in serotonin-immunoreactive fibers were observed in various parts of the brain of mice subjected to total asphyxia at 15 days of age, and the numbers of degenerated fibers decreased in almost all parts of the brain, the exception being the caudal portion of the brainstem, at 30 and 60 days of age. These results suggested that neonatal asphyxia induced permanent changes in the serotonin neuron system, with regional differences.

Animals

Chronic exposure to n-hexane induces changes in nerve-specific marker proteins in the distal peripheral nerve of the rat.

1. After long-term n-hexane exposure (2000 ppm, 12 h d-1, 6 d week-1, for 24 weeks), the content of neuron-specific enolase (gamma-enolase), creatine kinase-B and beta-S100 protein in the cortex, cerebellum, spinal cord and proximal and distal sciatic nerves of rats was determined by enzyme immunoassay. 2. The amounts of the three proteins decreased significantly in the distal segment of sciatic nerve, whereas they remained unchanged in the brain and proximal sciatic nerve. The quantitative decline in these marker proteins in the distal sciatic nerve could be related to neurophysiological deficits in the peripheral nerves. 3. This study indicates that the biochemical changes observed are consistent with the clinical and pathological findings of n-hexane neuropathy. These nerve-specific marker proteins can be used to assess solvent-related peripheral neurotoxicity.

Animals

Synthesis and antitumor activity of fused quinoline derivatives. III. Novel N-glycosylamino-indolo[3,2-b]quinolines.

Novel indolo[3,2-b]quinolines (1b-k), having a nitro, amino, acetamido, methanesulfonamido, or glycosylamino group at the 2, 7, or 8-position, were prepared and their antitumor activities against P388 leukemia in mice were examined. The 7-galactopyranosylamino derivative (1g) showed the most potent activity (optimal dose = 25 mg/kg, T/C greater than 333%, cure rate 5/6).

Animals

Effects of fatty acids, fatty amines and propylene glycol on rat stratum corneum lipids and proteins in vitro measured by fourier transform infrared/attenuated total reflection (FT-IR/ATR) spectroscopy.

Fourier transform infrared/attenuated total reflection (FT-IR/ATR) spectroscopy was used to examine the effect of fatty acids, fatty amines and propylene glycol (PG) on the molecular mobility of rat stratum corneum lipids and keratinized proteins, using a hydrophobic solute, indomethacin, and a polar solute, 5- and 6-carboxyfluorescein (CF). Treatment of the skin with either oleic acid or oleylamine resulted in significant CH2 C-H asymmetric stretching band shifts and broadening. The extent of spectral alteration varied with the chemical structure of the penetrant. The penetrants increased the lipophilic indomethacin flux and shortened the lag times through the skin in vitro. The plot of frequency changes vs. indomethacin flux or lag time demonstrated a linear relationship, thus indicating that spectral alteration in CH2 C-H stretching regions of stratum corneum lipids may provide a reliable index for characterizing penetrants. The data also showed that the hydrophilic group which attached to the CH2 group in the penetrant molecules did not play a part in the membrane permeability enhancing action. Oleic acid and oleylamine appeared to induce a conformational alteration of the keratinized proteins from alpha-helix to beta sheet. Such alteration was also observed with PG treatment. Accumulation of CF was significantly increased by the PG pretreatment of the skin, thus suggesting that PG-induced protein conformational changes could be related to the enhancement of CF accumulation.

Amines

Computer simulation of agglomeration in the Wurster process.

A simplified model for computer simulation of agglomeration in the Wurster coating process was constructed using droplet size distribution and the relation between the size of agglomerates and the number of primary particles composing them experimentally determined. Computer simulations were applied to the cases where a 2.5% aqueous solution of hydroxypropyl cellulose (containing sodium carboxymethyl cellulose of 10% on a dry basis) was sprayed on four kinds of sharply fractionized lactose powders between 32 and 75 microns. With cores larger than 53 microns, the agitation exerted on particles strongly suppressed the growth of agglomerates, but the fraction of produced agglomerates reached about 50%. The smallest droplet size that was contributable to agglomeration (critical droplet size) was estimated to be 37.1-49.0 microns, increasing with core size, and the weight fraction of droplets larger than this critical size was only 0.5-2.7%, decreasing with increase in core size. The production of even such a minor amount of coarse droplets could be responsible for significant agglomeration.

Chemistry, Pharmaceutical

Destabilization of whole skin lipid bio-liposomes induced by skin penetration enhancers and FT-IR/ATR (Fourier transform infrared/attenuated total reflection) analysis of stratum corneum lipids.

Whole skin lipid bio-liposomes (skin bio-liposomes), in size ranging from 2 to 8 microns, were prepared by a reverse phase evaporation technique using rat full thickness skin. Leakage of an encapsulated fluorescence probe, ANTS (delta-amino-1,3,6-naphthalene-trisulfonate), was measured by adding transdermal penetration enhancers (penetrants) into the medium where the skin bio-liposomes were present. Oleylamine induced a fast release of ANTS from the liposomes compared to lauryl-amine which showed a weak action. With these penetrants, the degree of ANTS release from the prepared bio-liposomes was found to correlate well with the results of frequency changes in the CH-asymmetric stretching band near 2920 cm-1 in the rat stratum corneum. The penetrant which caused relatively strong leakage of ANTS induced the significantly large shift of the peak toward the higher wave-numbers due to the perturbation in the structure of lipids of the stratum corneum. The skin bio-liposomes prepared from the rat full thickness skin could be useful in evaluating the penetrants.

Amines