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Biomedical subjects

A Kurihara

Publications and source records attributed to A Kurihara.

71 records · Page 4Linked to original sources
PubMed1981

Delayed-type hypersensitivity as revealed on the footpads of mice to azobenzenearsonate-acetyl bovine serum albumin.

A strong delayed-type footpad reaction was established in mice using azobenzenearsonate-acetyl bovine serum albumin (ABA-AcBSA) as an antigen. Male ddY/S mice were sensitized by subcutaneous injection of 100 microliter of Freund's complete adjuvant - saline (1:1) emulsion containing 100 microgram of the antigen and challenged by subcutaneous injection of 2.5 microliter of Freund's incomplete adjuvant - saline (1:1) emulsion with 2.5 microgram antigen in the footpad on the 10th day after the sensitization. The analysis of the system which fulfilled criteria for delayed-type hypersensitivity with regard to kinetics, passive transfer and histology of the footpad reaction, and the effect of dexamethasone, indomethacin and quinacrine on the footpad reaction were described.

Animals↗
PubMed1979

The surgical treatment of myelopathy secondary to rheumatoid arthritis of the lower cervical spine.

There are few reports in the literature of the surgical treatment of cervical myelopathy secondary to rheumatoid arthritis below the level of the axis. Three cases are presented. All had severe motor and sensory loss in the upper and lower extremities. The cause of myelopathy differed in each case: in the first, the dura mater was infiltrated with rheumatoid material; the second was due to a stenotic spinal canal narrowed by a fixed subluxation of the cervical spine; in the third, traction myelopathy resulted from sub-axial subluxation and posterior angulation combined with cervical instability. Neurological assessment is particularly difficult in patients with rheumatoid arthritis of the cervical spine. Skull or halo traction is useful to gauge neurological improvement, to reduce the dislocation and to immobilise the cervical spine before, during and after surgery. Surgery is considered where conservative treatment is either ineffective or not tolerated, and is indicated if severe myelopathy is evident or progressive. Anterior interbody fusion is the operation of choice for mobile subluxation. Laminectomy is recommended in fixed subluxation where compression of the cord is demonstrated on myelography.

Adult↗
PubMedDate not supplied

Retention of biologic activity of human epidermal growth factor following conjugation to a blood-brain barrier drug delivery vector via an extended poly(ethylene glycol) linker.

Human brain gliomas overexpress the receptor for epidermal growth factor (EGF), and radiolabeled EGF is a potential peptide radiopharmaceutical for imaging human brain tumors, should this peptide be made transportable through the blood-brain barrier (BBB) in vivo. Peptide drug delivery to the brain may be facilitated by conjugating peptide radiopharmaceuticals to BBB drug delivery vectors such as the OX26 monoclonal antibody (MAb), which undergoes receptor-mediated transcytosis through the BBB via the brain capillary endothelial transferrin receptor. EGF was biotinylated with NHS-XX-biotin, where NHS = N-hydroxysuccinimide and -XX- = bis (aminohexanoyl) spacer arm. The [125I]EGF-XX-biotin rapidly bound to C6 rat glioma cells transfected with the human EGF receptor. However, no binding to the C6 EGF receptor was detected when the [125I]EGF-XX-biotin was bound to a conjugate of streptavidin (SA) and the OX26 MAb. An alternative linker strategy using poly(ethylene glycol) (PEG) of 3400 Da molecular mass (PEG3400) was evaluated, wherein EGF was monobiotinylated with NHS-PEG3400-biotin. Attachment of the [125I]EGF-PEG3400-biotin to the OX26/SA conjugate did not impair binding of the construct to the EGF receptor in C6 glioma cells. The length of the -PEG- spacer arm and the -XX- spacer arm was >200 atoms and 14 atoms, respectively. These studies demonstrate that the use of the extended PEG linker releases steric hindrance of MAb transport vectors on binding of EGF to its cognate receptor on glioma cells. Attachment of EGF peptide radiopharmaceuticals to BBB drug delivery systems such as the OX26 MAb using extended PEG linkers allows for retention of the bifunctionality of the conjugate with binding to both EGF and transferrin receptors.

Animals↗
PubMedDate not supplied

Epidermal growth factor radiopharmaceuticals: 111In chelation, conjugation to a blood-brain barrier delivery vector via a biotin-polyethylene linker, pharmacokinetics, and in vivo imaging of experimental brain tumors.

Epidermal growth factor (EGF) is a potential peptide radiopharmaceutical for detection of brain tumors, because many human gliomas overexpress the EGF receptor (EGFR). The transport of EGF to the brain, however, is restricted by the blood-brain barrier (BBB). The purpose of the present study was to develop a vector-mediated brain delivery system for radiolabeled EGF. Human EGF was monobiotinylated with NHS-PEG3400-biotin, where NHS is N-hydroxysuccinimide and PEG3400 is poly(ethylene glycol) of 3400 Da molecular mass. EGF-PEG3400-biotin was radiolabeled with either 125I or 111In through the metal chelator, diethylenetriaminepentaacetic acid (DTPA). The radiolabeled EGF was then conjugated to a BBB delivery vector comprised of a complex of the OX26 monoclonal antibody (MAb) to the rat transferrin receptor, which was coupled to streptavidin (SA). Following intravenous injection in rats, the 125I conjugate was rapidly degraded in vivo, while the 111In conjugate was metabolically stable. The brain delivery of [111In]DTPA-EGF-PEG3400-biotin was enabled by conjugation with OX26/SA and was optimized by co-injection of unlabeled EGF to saturate EGF receptors in the liver. The specific binding of the [111In]DTPA-EGF-PEG3400-biotin conjugated to OX26/SA to the EGF receptor was confirmed in C6 rat glioma cells, which had been transfected with a gene encoding for the human EGF receptor under the regulation of a dexamethasone-inducible promoter. In vivo studies of C6-EGFR experimental tumors in Fischer 344 rats demonstrated successful brain imaging only when the peptide radiopharmaceutical was conjugated to the BBB delivery system, although the C6-EGFR tumors did not express EGFR in vivo. In conclusion, these studies describe the molecular formulation of a peptide radiopharmaceutical that can be used for imaging brain tumors behind the BBB.

Animals↗
PubMedDate not supplied

Abeta(1-40) peptide radiopharmaceuticals for brain amyloid imaging: (111)In chelation, conjugation to poly(ethylene glycol)-biotin linkers, and autoradiography with Alzheimer's disease brain sections.

The amyloid plaques of Alzheimer's disease (AD) are formed by the neuropeptide Abeta(1)(-)(42/43), and carboxyl terminal truncated forms of this neuropeptide, designated Abeta(1)(-)(40), bind to amyloid plaques of AD autopsy tissue sections. Therefore, Abeta(1)(-)(40) is a potential peptide radiopharmaceutical that could be used for imaging brain amyloid in living subjects with AD, should this neuropeptide be made transportable through the blood-brain barrier (BBB). To accomplish this, the neuropeptide must be modified to enable (i) attachment to a BBB drug targeting system and (ii) labeling with a radionuclide, e.g., 111-indium, suitable for brain imaging by external detection modalities such as single photon emission computed tomography (SPECT). The present studies describe the synthesis of an Abeta(1)(-)(40) analogue that contains a biotin at the amino terminus and a diethylenetriaminepentaacetic acid (DTPA) moiety conjugated to one of the internal lysine residues. The DTPA-[N-biotin]-Abeta(1)(-)(40) was purified by gel filtration fast-protein liquid chromatography (FPLC) using two Superose 12HR columns in series, and the structure of the purified peptide was confirmed by matrix-assisted laser desorption ionization (MALDI) mass spectrometry. The binding of the [(111)In]DTPA-[N-biotin]-Abeta(1)(-)(40) to amyloid plaques of AD autopsy tissue sections was demonstrated by film and emulsion autoradiography. A poly(ethylene glycol) (PEG) linker of 3400 Da molecular mass, designated PEG(3400), was inserted between the Abeta(1)(-)(40) and the biotin moiety, but this modification diminishes binding of Abeta(1)(-)(40) to the AD amyloid plaques. In summary, these studies describe a novel formulation of biotinylated Abeta(1)(-)(40) that allows radiolabeling with 111-indium. The peptide radiopharmaceutical may be conjugated to an avidin-based BBB drug targeting system to enable transport through the BBB and imaging of brain amyloid in vivo.

Alzheimer Disease↗
PubMedDate not supplied

Lumbar disc herniation in children and adolescents. A review of 70 operated cases and their minimum 5-year follow-up studies.

Seventy cases of surgically documented herniated lumbar disc in children and adolescents were analyzed. Twenty-six of the 70 cases were followed at least five years postoperatively. The incidence of juvenile disc herniation in Japanese patients appear to be much higher than in Caucasians. Repeated trauma may be an important etiological factor of herniated lumbar disc in this age group. The history and physical findings in children and adolescents are not fundamentally different from those in the adult, although abnormal neurological findings are not common. Five-year follow-up studies suggest that interlaminal laminectomy without fusion is the best procedure when surgical treatment of herniated lumbar disc is necessary in children and adolescents.

Adolescent↗
PubMedDate not supplied

Pharmacokinetics of RU44403, an active form of newly developed angiotensin-converting enzyme inhibitor (RU44570) in the rat.

Trandolapril (RU44570) is an ethyl ester prodrug of trandolprilat (RU44403) having angiotensin I-converting enzyme (ACE) inhibitory activity. Disposition of RU44403 was investigated by oral or intravenous administration of RU44570 (0.1, 1, and 3 mg/kg p.o. or 1 mg/kg i.v.) and RU44403 (0.94 mg/kg p.o.) to rats. Orally dosed RU44403 was scarcely absorbed from the gastrointestinal tract (3% of dose), whereas its prodrug was found to be rapidly absorbed (32.1-45.7% of dose) and completely transformed to RU44403, giving maximum plasma concentration within 0.5 hr. Regardless of both dose level and route of administration, almost similar plasma concentrations of RU44403 were observed in the terminal phase following doses of RU44570, resulting in prolonged elimination half-life, 89.01, 63.29, and 62.64 hr for 0.1, 1, and 3 mg/kg p.o. and 63.52 hr for 1 mg/kg i.v., respectively. Furthermore, oral AUC0-infinity of 0.1 mg/kg RU44403 was not dose proportional, suggesting nonlinear pharmacokinetic profile. To elucidate the factors causing the nonlinear disposition, a dissociation constant of the active metabolite in plasma was determined using a one-compartment model in which free RU44403 in plasma was the sole form available for elimination from the compartment. The value of the constant was 0.024 nM, which was closely similar to that of the high-affinity binding site of plasma protein determined by the ultrafiltration method in vitro. Also, both values were comparable with an inhibitor constant of RU44403 to ACE in plasma that was obtained by Henderson's plot for a kinetic analysis of the tight binding of an enzyme and inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗