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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 595 records · Page 33Linked to original sources
PubMed1992

Mechanisms in the development of limbic status epilepticus and hippocampal neuron loss: an experimental study in a model of status epilepticus induced by kindling-like electrical stimulation of the deep prepyriform cortex in rats.

A new model of status epilepticus (SE), which was induced by intermittent electrical stimulation (20 Hz for 20 sec every min for 180 min) of the deep prepyriform cortex, has been developed in the conscious rat. SE was induced in 9 of 16 rats in the drug-free group. The number of stimulation trains required to induce SE in this status subgroup was 125.6 +/- 12.7 (mean +/- SEM) and the mean duration of self-sustained seizure activity (SSSA) occurring after cessation of the stimulation session was 295.4 +/- 111.4 min. Some animals showed secondary generalized seizures. Significant cell loss was observed in the hippocampal CA3 pyramidal cell layer ipsilateral to the stimulation site and bilateral CA1 areas in the status subgroup compared with the group subjected to sham operation. In addition, there was a significant negative correlation between the duration of SSSA subsequent to the stimulation session and the total number of intact pyramidal neurons observed in the bilateral CA1 and ipsilateral CA3 subfields of the status subgroup. There were significant differences between the status and non-status subgroups with respect to the number of afterdischarges (ADs) and the total AD duration during the stimulation session. Pretreatment with phenobarbital (30 mg/kg) prevented the development of SE and hippocampal cell loss completely. Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist (0.25 or 1 mg/kg), also prevented hippocampal cell loss, although it did not block SE generation completely, which suggests dissociation of the mechanisms underlying the development of SE and hippocampal damage. These results indicate that prolonged SSSA actually causes hippocampal damage and it is critically dependent upon NMDA receptor participation.

Animals↗
PubMed1992

Role of monocyte colony-stimulating factor in foam cell generation.

Recently, we reported that human monocyte colony-stimulating factor (M-CSF) stimulates the clearance of lipoproteins containing apoB100 via both low density lipoprotein receptor-dependent and -independent pathways in target cells of M-CSF, and reduces plasma cholesterol level (Journal of Biological Chemistry, 265:12869-12875, 1990). This suggests a linkage of cytokines to the metabolic regulation of plasma cholesterol. Furthermore, we found a significant role of M-CSF in cholesterol metabolism of human monocyte-derived macrophages. M-CSF enhanced not only the uptake of acetylated low density lipoprotein and oxidized low density lipoprotein in macrophages, but also the efflux of cholesterol from cholesterol-loaded macrophages. To elucidate in vivo effects of M-CSF on cholesterol efflux from tissues, we administered an intravenous injection of 3H-cholesterol (150 microCi) into WHHL rabbits 1 month before starting M-CSF treatment. We observed an increased cholesterol efflux from tissues to plasma high density lipoprotein after M-CSF treatment when cholesterol efflux was estimated as the change in specific radioactivity of plasma high density lipoprotein-cholesterol. This result suggests that M-CSF can enhance the excretion of cholesterol from target cells of M-CSF, such as cholesterol-loaded macrophages in the arterial wall, and reduce the rate of atherogenesis.

Cells, Cultured↗
PubMed1992

Detection of three separate DNA polymorphisms in the human lipoprotein lipase gene by gene amplification and restriction endonuclease digestion.

A rapid detection method was developed for DNA polymorphisms in the human lipoprotein lipase (LPL) gene. The examined polymorphisms include an A-C transversion in the 5'-region of intron 3, a T-G transversion that occurs within a Hind III site of intron 8, and the previously described C-T transition that causes a Pvu II polymorphism in intron 6. Gene fragments encompassing each polymorphic site were amplified by the polymerase chain reaction (PCR) and digested with an appropriate restriction enzyme whose recognition site was either naturally affected by the polymorphism or artificially created with a mismatched PCR-primer. According to the digestion profiles, genotypes were unambiguously distinguished. With this method, respective allelic frequencies were determined for 50 or 70 normal subjects. The procedure will facilitate LPL genotyping in the large population.

Base Sequence↗
PubMed1992

[Clinical assessment of 99mTc-HMPAO scintigraphy in thoracic tumors].

99mTc-hexamethylpropylene amineoxime (99mTc-HMPAO) scintigraphy was performed in 15 malignant tumors in 11 patients and a patient with bronchopneumonia. A high 99mTc-HMPAO affinity for the tumors was observed on SPECT, however, the mean tumor/contralateral normal lung ratios of 99mTc-HMPAO activity (1.26) was lower than that of 201Tl-chloride (2.29). 99mTc-HMPAO uptake was seen not only in the tumors but also in the bronchopneumonia, atelectasis, and irradiated lung (containing radiation fibrosis). Moreover, a diffuse uptake in the lung was seen in a patient received repeated chemotherapy. Therefore, it is emphasized that there is a non-specific 99mTc-HMPAO uptake in those various pulmonary conditions.

Adult↗
PubMed1992

[A case of squamous cell carcinoma of urinary bladder with an ileo-vesical fistula detected on bone scintigraphy].

A case of squamous cell carcinoma of the urinary bladder with concomitant radionuclide uptake in the colon observed on bone scintigram in a 76-year-old female is presented. This finding reflected retrograde flow from the bladder to the intestine and suggested the presence of vesicoenteric fistula. The patient's pelvis had been irradiated with 23.4 Gy before the bone scintigram, she had been complaining only of diarrhea and not of any characteristic symptoms of vesicoenteric fistula, such as pneumaturia and fecaluria. Further examination including cysternography revealed a fistulous communication between the bladder and the ileum. The size of the tumor decreased markedly after radiation, tumor invasion to the ileum and the fistulous communication were verified at surgery.

Aged↗
PubMed1992

[Experimental study on 123I-IMP kinetics in irradiated lung of rabbit].

Radiation-induced alteration of intra-pulmonary kinetics of 123I-IMP was investigated in 11 rabbits received a 50 Gy dose of radiation to the hemithorax. In all of these rabbits examined during 3-17 weeks following the irradiation, an abnormal accumulation was seen in the irradiated lung on the delayed image obtained 60 minutes after the injection of 123I-IMP. The time-activity curves in the irradiated lung following the injection had shallower downslopes of both the initial fast phase and the following slow phase than those of non-irradiated lung, and finally 123I-IMP uptake of the irradiated lung exceeded that of the normal lung. Chest radiographies all of 11 rabbits showed no abnormal shadow and histological studies in 6 of them revealed a relatively slight change or injury of the irradiated lung during 3-17 weeks. These results indicate that this agent may be useful for detecting and assessing relatively early and slight lung injury induced by irradiation.

Amphetamines↗
PubMed1992

[Bone scintigraphy in two cases with cough related stress fractures of rib].

Two patients of unusual cough related stress fractures of the ribs are presented. Both patients complained of cough and chest pain with respiratory infection, and the initial chest radiographs showed only an infiltrative shadow due to bronchopneumonia in the lung field, however, failed to reveal any definite osseous abnormality of the ribs. Follow up chest radiographs revealed a callus formation in the fracture sites. In both patients, fracture sites were multiple and located at the axillary line, and radionuclide bone scan disclosed focal abnormal concentrations of activity in these characteristic locations of the lesions. Moreover, there were abnormal accumulation sites in the adjacent above and below ribs, and this finding also seemed to be characteristic of cough related stress fractures of the ribs.

Adult↗
PubMed1991

Occurrence of multiple aberrantly spliced mRNAs upon a donor splice site mutation that causes familial lipoprotein lipase deficiency.

A donor splice site mutation was found in the lipoprotein lipase (LPL) gene of a patient with familial LPL deficiency. The mutation, a G----A substitution, occurred at the first nucleotide of intron 2. Northern blot analysis of total RNA from the patient showed strikingly low levels of LPL-specific mRNAs. Using the polymerase chain reaction, the LPL mRNA splicing was analyzed in detail. The results demonstrated that no normal splicing occurred at the authentic splice site; rather a cryptic splice site 18 bases upstream from the mutation site was preferentially utilized. Although the resulting alteration in mRNA was a minute in-frame 18-base deletion, the amount of the abnormal transcript was only 1/12 that of the normal. In addition to this major cryptic splice site, we also identified multiple minor sites which were utilized at extremely lower efficiencies. Unexpectedly, one of these minor sites was also used as an alternative splice site in the normal subject at a comparably low efficiency. The sequences of these minor cryptic sites possessed many of the characteristics common to those of other normal splice sites, indicating that even such minor sites should have also been selected according to the general rules for splice site selection. These results demonstrate that upon mutation, a broad spectrum of cryptic splice sites is activated in vivo at the sites' respective efficiencies.

Adult↗
PubMed1991

The effect of apo E secretion on lipoprotein uptake in transfected cells.

To investigate the role of apolipoprotein E (apo E) secreted by peripheral tissues in local lipoprotein metabolism, we developed a cell strain that constitutively produced and secreted apo E. A fusion plasmid containing rat apo E genomic DNA under control of mouse metallothionein promotor was constructed and transfected into Chinese hamster ovary cells. A stable transformant designated CHO-MAEII constitutively secreted rat apo E mainly in the form of sialylated free protein. The secretion was further enhanced by metal induction up to 1 micrograms apo E/ml per 12 h. When incubated with 125I-labeled very low density lipoprotein (125I-VLDL) at 37 degrees C, CHO-MAEII took up and degraded 125I-VLDL with higher affinity than control cells. Furthermore, considerable amount of methylated 125I-VLDL was degraded by CHO-MAEII, while no methylated 125I-VLDL was degraded by control cells. No significant differences were found in the uptake of 125I-LDL. The data indicated that apo E molecules secreted by CHO-MAEII were transferred to 125-VLDL particles, which caused a higher affinity of these particles for LDL receptors on the cells. It is suggested that apo E secreted from peripheral tissues enhances the uptake of lipoproteins by themselves or by surrounding cells in the local environment which demand cholesterol and express LDL receptors. CHO-MAEII was a good model for these 'auto- or paracrine-like functions' of apo E.

Animals↗
PubMed1991

Kindling-induced persistent alterations in the membrane and synaptic properties of CA1 pyramidal neurons.

Intracellular recordings of CA1 pyramidal cells were performed in in vitro hippocampal slices obtained from control and amygdala- or perforant path-kindled rats. Passive membrane properties did not differ between control and kindled cells. Twenty-three percent of kindled cells, however, displayed burst firing with depolarizing current injection, whereas no control cells produced bursts (P less than 0.01). Two different types of voltage-dependent alteration of depolarizing postsynaptic potentials (PSPs) were also evident in kindled cells. The majority (26/29) of these cells showed a smaller increase (type 1, n = 18), or a sudden decrease (type 2, n = 8), in PSP amplitude with passive membrane hyperpolarization when compared to controls (P less than 0.01). The NMDA antagonist D-APV did not markedly alter the overall slope of the PSP/membrane potential function in either 'type 1' or 'type 2' cells, suggesting that neither behavior was due to a change in the activation characteristics of NMDA receptors. The amplitude of IPSPs was smaller in 'type 1' kindled cells (P less than 0.05) than in controls, however, suggesting that the reduced slope of the PSP/membrane function may be accounted for by a change in inhibition.

Action Potentials↗
PubMed1991

Differential phenotypic expression by three mutant alleles in familial lecithin:cholesterol acyltransferase deficiency.

Familial deficiency of lecithin:cholesterol acyltransferase (LCAT) is an autosomal recessive disorder characterised by abnormalities of all plasma lipoprotein classes and by abnormal deposition of unesterified cholesterol in tissues. To elucidate the molecular basis of the disease, the LCAT genes of three unrelated Japanese patients were amplified by means of the polymerase chain reaction. Direct sequencing of the amplified fragments covering all exons and junctions showed that the patients are homozygotes for separate gene mutations. In one patient a 3 bp insertion, which should cause a substantial change in the enzyme structure, was found in exon 4; he had near absence of LCAT mass and activity. Two separate missense mutations were identified in exon 6 of the other two patients, who produced functionally defective enzymes that differed widely in specific activity. The replacement of asparagine228 with positively charged lysine completely abolished enzyme activity, whereas the other, conservative, aminoacid substitution (methionine293----isoleucine) gave rise to a partially defective enzyme. These results show that distinct mutations cause differences in plasma LCAT activity and LCAT mass, ultimately leading to differential phenotypic expression of familial LCAT deficiency.

Adult↗
PubMed1991

The enhanced cellular uptake of very-low-density lipoprotein enriched in apolipoprotein E.

We have recently reported an increased clearance of plasma very-low-density lipoprotein (VLDL) after intravenous injection of apolipoprotein (apo) E in Watanabe heritable hyperlipidemic (WHHL) rabbits. In the present study, we have investigated the cellular uptake of VLDL enriched in apo E (VLDL-E) which had been incubated with purified rabbit apo E. VLDL-E was taken up approx. 2-fold more than VLDL in human skin fibroblast, human monocyte-derived macrophage and Hep G2 cell and its degradation was least in macrophage. To characterize the binding of VLDL-E, we performed a binding assay using hepatic endosome isolated from estradiol-treated rats and we observed both increased EDTA-sensitive and -resistant binding of VLDL-E on endosome. Ligand blotting of hepatic endosome demonstrated two major bands of LDL receptor (130 and 260 kDa protein) and a minor band of LDL receptor-related protein (580 kDa protein) with a ligand of VLDL-E. These results suggested that VLDL-E was endocytosed in liver through a similar pathway among three cell types, and enrichment of apo E in VLDL enhanced the uptake of VLDL not only via an EDTA-sensitive binding site (classical LDL receptor) but also via other binding sites including an EDTA-resistant binding site and an LDL receptor-related protein.

Animals↗
PubMed1991

Selective dopamine D1 and D2 agonists independently affect different components of the free-running circadian rhythm of locomotor activity in rats.

The effects of selective dopamine D1 (SKF 38393) and D2 (4-propyl-9-hydroxynaphthoxazine or PHNO) agonists on free-running rhythms of locomotor activity in rats were investigated under either constant light (LL) or dark (DD) condition. Rats under the DD condition exhibited clear circadian patterns of activity, while circadian patterns of activity in animals kept under the LL condition were more ambiguous. Under the DD condition, SKF 38393 significantly increased the length of the period of free-running rhythms of locomotor activity but had no effect on the amplitude and the mesor, while PHNO significantly increased the amplitude and the mesor of free-running rhythms but had no effect on the length of the period.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Sequential gadolinium-DTPA enhanced MRI studies in neuro-Behçet's disease.

Sequential gadolinium-DTPA (Gd-DTPA) enhanced MR images were obtained before and after steroid therapy in a case of neuro-Behçet's disease. Multiple scattered lesions, which could not be detected on pre- and post-contrast CT, were demonstrated mainly in the white matter of the pons and/or the cerebrum with both T1- and T2-weighted images. Some of these lesions, however, were not enhanced at all by infusion of Gd-DTPA. The Gd-DTPA infusion study demonstrated marked enhancement in the white matter of the pons and cerebrum. Some lesions not seen with T2-weighted images were also strongly enhanced by Gd-DTPA infusion at the acute stage. After steroid therapy, the symptoms and abnormal laboratory findings were resolved. The pontine and cerebral lesions on plain MR images remained unchanged even after resolution of the symptoms, suggesting that they were inactive old foci. On the other hand, the lesions detected in the enhancement study before steroid therapy disappeared with the repeat Gd-DTPA enhanced MR images hich were performed after resolution of the symptoms. Some active inflammatory lesions in neuro-Behçet's disease may be demonstrated only on Gd-DTPA enhanced MR images. Gd-DTPA enhanced MR imaging appears to be potentially useful for detecting active inflammatory lesions in neuro-Behçet's disease and for evaluating the efficacy of treatment.

Behcet Syndrome↗
PubMed1991

Antitumor activity on murine tumors of a novel antitumor benzoylphenylurea derivative, HO-221.

A novel antitumor compound, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea (HO-221) was evaluated for its antitumor activity in experimental tumor models. HO-221 preparation was given orally to tumor-bearing animals. The compound exhibited significant effects against various tumors such as P388 and L1210 leukemias; M5076 reticulum-cell sarcoma; colon 38 carcinoma; human xenografts MX-1, LX-1, GA-1, and Co-1; Lewis lung carcinoma; sarcoma 180; and Walker 256 carcinosarcoma and was especially effective against solid tumors. However, its effect on murine B16 melanoma was moderate. Intermittent administration of HO-221 produced better results. The effects of HO-221 on human tumor xenografts were compared with those of other antitumor agents. HO-221 showed activity against LX-1 lung and Co-1 gastrointestinal tumor and was also effective against advanced-stage L1210 leukemia and Lewis lung carcinoma. Furthermore, the effect of HO-221 on drug-resistant tumors was examined using murine leukemias L1210 and P388. It showed no cross-resistance with the known antitumor agents Adriamycin (ADM), daunomycin (DM), vincristine (VCR), mitomycin C (MMC), cisplatin (CDDP), 5-fluorouracil (5-FU), cytosine arabinoside (Ara-C), methotrexate (MTX), cyclophosphamide (CPA), or carboquone (CQ), and collateral sensitivity to HO-221 was found in MMC-, CDDP-, and CPA-resistant sublines. HO-221 exhibits significant reproducible, broad-spectrum antitumor activity against experimental tumors as well as human neoplasms.

Animals↗