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Biomedical subjects

M Hirayama

Publications and source records attributed to M Hirayama.

At least 163 records · Page 9Linked to original sources

Kinetics of internalization and cytotoxicity of transferrin-neocarzinostatin conjugate in human leukemia cell line, K562.

Human serum transferrin was conjugated with an anticancer-active polypeptide, neocarzinostatin, by using N-succinimidyl 1-3-(2-pyridyldithio)propionate. The conjugate consisted of 1.8 mol of neocarzinostatin per 1 mol of transferrin on average and retained cytotoxic activity against human tumor cells. This conjugate was capable of binding to the transferrin receptor of human myelogenous leukemia K562 cells and was internalized by endocytosis. The LD50 values of the conjugate and neocarzinostatin alone in the presence of excess native bovine transferrin were 0.20 microgram/ml and 1.80 micrograms/ml, respectively, suggesting that the effect of the conjugate was greater than that of neocarzinostatin alone. A pulse-chase experiment using 125I-labeled conjugate revealed that 25% of the internalized conjugate was degraded in lysosomes and the rest was recycled back to the cell surface without degradation. About 75% of this conjugate recycled back to the cell surface in 18.3 min (3.4 min for receptor binding and 14.9 min for recycling to the cell surface through the acidosomes), while the rest was delivered from the cell surface to the lysosome in 19.6 min. This phenomenon was confirmed by chasing the radioactivity in subcellular fractions separated by Percoll density gradient centrifugation. Therefore, it was concluded that this conjugate is internalized specifically by transferrin receptors and is at least partly transferred to and accumulated in lysosomal compartments, resulting in the inhibition of cellular DNA synthesis.

Antibiotics, Antineoplastic↗

[Quantification of tenderness of masticatory muscle].

As more dentists diagnose and treat the patient with temporomandibular disorders, muscle palpation has been recognized as a valuable diagnostic method. But this method was depended on sensibility and experience of the operator. The purpose of this study was to establish the quantification of muscle palpation by new pressure pain threshold apparatus. Pressure pain threshold (PPT) was determined by the subject when a ramp force applied to the skin changed from "pressure" to "pain". The subjects for the experiments were 90 normal males, 100 normal females and one patient with temporomandibular disorders. Total of 12 sites, anterior temporal M., posterior temporal M., superficial portion of masseter M. and deep portion of masseter M., were measured. The results obtained were as follows: 1. The females showed lower PPT than the males. 2. No difference of PPT between right and left sides was recognized in normal subject, but the significant difference in the patient. 3. PPT of the normal subjects were significantly higher in the posterior temporal M. than the other sites and lower in the superficial portion of masseter M. than the other sites.

Facial Pain↗

[Measurement of gamma-interferon in sera and CSF in patients with multiple sclerosis and inflammatory neurological diseases].

We examined whether gamma-interferon (gamma-IFN) can be detected in serum and CSF of patients with multiple sclerosis and other inflammatory neurological diseases. Gamma-IFN was assayed by solid phase radioimmunoassay on the forward sandwich principle. In 7 serum samples in acute stage of multiple sclerosis without corticosteroid, in 2 CSF samples in acute stage, gamma-IFN was not detected. In stable stage there was no case with positive gamma-IFN. The patient with tuberculous meningitis showed high titer in CSF but not in serum. One case with herpes zoster meningitis, one case out of 2 aseptic encephalitis showed positive gamma-IFN in CSF. In one case with Vogt-Koyanagi-Harada disease, gamma-IFN was detected both in serum and CSF. One case with Neuro-Behçet syndrome showed positive gamma-IFN in CSF. No gamma-IFN was detected in 2 cases with Guillain-Barré syndrome, one case with Crow-Fukase syndrome, Fisher syndrome, 2 cases with polymyosits. gamma-IFN in CSF was detected in meningitis and encephalitis, but not in serum. This suggests that the locally infiltrating cells produce gamma-IFN. However, we could not detect gamma-IFN in either CSF or serum of patients with multiple sclerosis. Negative results of gamma-IFN in patients with multiple sclerosis can be interpreted in 2 ways. 1. The half life of gamma-IFN is very short in vivo, and the level of gamma-IFN may not be detected at the time of sampling. 2. Generalized augmentation of gamma-IFN production may not be observed but locally infiltrating cells or astrocytes might produce gamma-IFN.(ABSTRACT TRUNCATED AT 250 WORDS)

Behcet Syndrome↗

[The study of anti-oligodendrocyte antibody in sera, and CSF of patients with multiple sclerosis].

We studied anti-oligodendrocyte antibody in sera and CSF from patients with multiple sclerosis (MS) and other neurological diseases (OND) by enzyme-linked immunosorbent assay (ELISA). Oligodendrocytes were isolated by percoll density gradient from brains of 4 week-old rat and cultured in poly-1-lysine-coated 96 well microwell plate. After overnight culture, oligodendrocytes were fixed in 0.5% glutaraldehyde and stored at -20 degrees C. ELISA was performed using peroxidase-conjugated goat anti-human IgG (Fab')2 as usual. Serum and CSF were examined at dilution of 1:400 and 1:2 respectively, and O.D. was read at 490 nM. In sera from patients with MS and OND, the titer of anti-oligodendrocyte antibody was significantly higher than those from normal controls. However, there was no significant difference between MS and OND. Significantly higher titer of anti-oligodendrocyte antibody was observed in CSF from patients with meningoencephalitis and polyradiculoneuropathy. However, comparing CSF anti-oligodendrocyte antibody per CSF IgG, there was no significant difference among each group. There was no significant correlation between the cytotoxicity index of sera and anti-oligodendrocyte antibody level. There might be additional cytotoxic factor other than anti-oligodendrocyte antibody. Our data support the idea anti-oligodendrocyte antibody is not specific to MS, and the role of anti-oligodendrocyte antibody in the pathogenesis of MS is secondary.

Animals↗

X-linked recessive bulbospinal neuronopathy. A clinicopathological study.

A clinicopathological study on X-linked recessive bulbospinal neuronopathy was undertaken on 9 cases, with morphological observations on 3 autopsied cases and sural nerve biopsies from 6 patients. Both lower motor and primary sensory neurons were involved. Lower motor neurons were markedly depleted through all spinal segments and in brainstem motor nuclei except for the third, fourth and sixth cranial nerves. Primary sensory neurons were less severely affected. A quantitative study of primary sensory axons at several levels in the peripheral nervous system suggested that a distally accentuated axonopathy was the salient pathological process. Segmental demyelination and remyelination clustered on individual fibres, and g ratios (axon diameter: total fibre diameter) in the sural nerve showed an increased scatter in some cases. Evidence of regeneration was inconspicuous. Unmyelinated fibres were well preserved throughout all the nerves examined. Neurons in the Onufrowicz nuclei, in the intermediolateral columns and in Clarke's columns of the spinal cord were generally well preserved. These observations indicate that a lower motor and primary sensory neuronopathy is a major neurological manifestation in this disease.

Aged↗

Infection of human T-lymphotropic virus type I to astrocytes in vitro with induction of the class II major histocompatibility complex.

To clarify the pathogenesis of human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM), we examined whether HTLV-I infects normal human glial cells in vitro with induction of the major histocompatibility complex (HMC) class II antigen by immunofluorescence method. It was found that about 10% of astrocytes were infected with HTLV-I with induction of class II MHC antigen. Fluorescence-conjugated HTLV-I was adsorbed to 10% of astrocytes. On the contrary, there was no class II MHC antigen expression and very few HTLV-I infection on oligodendrocytes. We speculated that in patients with HAM, HTLV-I-specific, MHC class II antigen restricted, activated CD4+ cells could damage the MHC class II antigen + HTLV-I-infected astrocytes, leading to the disturbance of blood-brain barrier and to the destructive lesion in the central nervous system.

Astrocytes↗

Late-onset acid maltase deficiency associated with intracranial aneurysm.

The autopsy findings in a patient with late-onset acid maltase deficiency who died following rupture of a basilar artery aneurysm are reported. The patient developed muscular weakness and wasting at the age of 20 years and died 9 years later after suddenly falling into a coma. At autopsy a giant fusiform aneurysm was found in the basilar artery which had ruptured at the base of the pons, leading to a large haematoma in the pons. The cerebral arteries and arterioles showed extensive vacuolar degeneration of smooth muscle cells in the media. It is suggested that the aneurysm was induced by fragility of the arterial wall due to this smooth muscle change.

Adult↗

[Blood polymorphism in the study of isolated communities].

Isolated communities offer a unique opportunity for the study of biological and social consequences of consanguinity and migration. The studies of genetic polymorphisms have contributed greatly, not only to knowledge of the genetic constitution of a given individual and population, but also to clarify either relationship between structure and function of polymorphic traits or the susceptibility to multifactorial diseases, in which interaction between the gene and environment cannot be ignored. For over 25 years, we have investigated the effect of consanguinity and genetic polymorphisms in 9 isolated communities in Western Japan. We reported here different values of gene frequency for each polymorphic trait, compared with the neighboring communities and described how we applied these data to clarification of the genetic constitution of isolated communities as well as of genetic susceptibility to some diseases.

Anemia, Aplastic↗

[Intraperitoneal (Ip) administration of cisplatin in combination with systemic chemotherapy in patients with malignant ascites of gastrointestinal cancer: clinical evaluation and pharmacokinetics].

Ten patients with carcinomatous peritonitis of gastrointestinal cancer have been treated with administrations of CDDP-Ip (50-150 mg/body), in combination with systemic chemotherapy simultaneously combined with sodium thiosulfate (STS) iv in 4 patients. All patients received transfusions of specific hydration. The pharmacokinetics of CDDP was studied in 4 patients, and the following results were obtained. (1) As for its effect on malignant ascites, according to Koyama's and Saito's criteria, 2 patients showed a complete response, 3 showed a partial response, and 5 showed no change. (2) As for its effect on the primary site, only one patient showed a partial response, and the others no change. (2) As to its side effects, 6 patients manifested nausea and vomiting, and only one showed a mild kidney dysfunction, and no myelosuppression. No significant difference in the side effects between the STS-combined group and the non-STS-combined group was found. (3) Serum CDDP levels were reached maximum 1-2 hours after Ip, and gradually decreased during the beta-phase of iv administration. Significant levels of non-protein-bound CDDP were found in the serum within 4 hours after Ip. These results indicate that the CDDP Ip is safe and useful for carcinomatous peritonitis of gastrointestinal cancer, however the combination of STS might weaken the systemic anti-cancer effect of CDDP by neutralizing the non-protein-bound CDDP in the serum.

Aged↗