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Biomedical subjects

T Yoshimoto

Publications and source records attributed to T Yoshimoto.

At least 19 recordsLinked to original sources
PubMed1992

Structure and chromosomal localization of human arachidonate 12-lipoxygenase gene.

Arachidonate 12-lipoxygenase introduces a molecular oxygen into the C-12 position of arachidonic acid to produce 12(S)-hydroperoxy-5,8,10,14-eicosatetraenoic acid. With the aid of cDNA probes for the enzyme, we isolated overlapping lambda clones encompassing the human 12-lipoxygenase gene and flanking regions from a human genomic library. The gene consists of 14 exons with 13 introns and spans approximately 15 kilobases of DNA. All the exon-intron junctions conform to the GT/AG rule. Neither a typical TATA box nor a CAAT box was found in approximately 1-kb sequence of 5'-upstream region of the translation initiation site. However, this region contains several regulatory elements including four GC boxes, two CACCC boxes, three AP-2 binding sequences, and a glucocorticoid-responsive element. The major transcription initiation site was determined by primer-extension analysis as an adenosine residue at 306 bases upstream from the translation initiation codon. The chromosomal localization of the human 12-lipoxygenase gene was examined by fluorescence in situ hybridization, and the gene was assigned to the sub-band p13.1 of chromosome 17.

Arachidonate 12-Lipoxygenase↗
PubMed1992

[Analysis on combined effect of X-rays with 5-FU on rat subcutaneous gliomas].

In a series of experiments on the combined use of radio- and chemotherapy for malignant glioma, X-rays combined with ACNU or 5-FU treatment caused a supra-additive effect on multicellular spheroids in vitro. In the present experiment, the effect of X-rays combined with 5-FU treatment on subcutaneously transplanted rat gliomas of RGC-6 cells was analyzed. The dose-survival curve for X-rays given to tumors in air-breathing rats was biphasic with a terminal slope (D0 = 4.3 Gy) that was parallel to that for tumors in previously killed rats. The hypoxic cell fraction thus obtained from the ratio of the surviving fraction in two parallel curves at 20 Gy was about 7% in the subcutaneous tumors in air-breathing rats. X-ray-induced, potentially lethal cellular damage recovered within 8 hours in these tumors. The surviving fraction of cells in the tumors decreased to a minimum at 4-6 hours after a 5-FU injection, but increased thereafter. A biphasic dose-response curve for 5-FU was also obtained for cells in these tumors, indicating the presence of 5-FU resistant cells. The effect of X-irradiation given at about 8 hours after a 5-FU injection was greater than the additive effect of both agents acting independently. This was true when an X-ray dose of more than 5 Gy was given.

Animals↗
PubMed1992

Molecular structure and function of the porcine arachidonate 12-lipoxygenase gene.

The gene encoding arachidonate 12-lipoxygenase was cloned from a porcine EMBL3 genomic library using a cDNA probe of the enzyme, and its nucleotide sequence was determined. The gene consists of 14 exons with 13 introns, and spans approximately 8 kilobases. Analysis of splice junctions indicated that all of the splice donor and acceptor sites conformed to the GT/AG rule. An approximately 1-kilobase region upstream of the coding sequence contains nine GC-boxes for potential Sp1-binding sites at positions -77, -135, -145, -165, -214, -636, -643, -684, and -813. There are two sets of AP-2 binding sequence at positions -234 and -402. Neither typical TATA box nor CCAAT box is found in this region. The transcriptional start site was determined by primer extension analysis, and was tentatively identified as a cytidine residue located 19 bases upstream from initiation codon. Southern blot analysis revealed the presence of one copy of 12-lipoxygenase gene per haploid genome. We found striking similarities in genomic organization as well as the promoter sequences between the porcine 12-lipoxygenase and the rabbit 15-lipoxygenase genes, suggesting that these genes are evolutionarily related.

Amino Acid Sequence↗
PubMed1992

Interstitial deletion of chromosome 16q: 16q22 is critical for 16q- syndrome.

Partial deletion of 16q is rare; to our knowledge only 12 cases have been published. Fryns et al. [Hum Genet 38:343-346, 1977] described the first of these cases and proposed a new clinical entity. Our patient was a girl and had many minor anomalies of the kind often observed in 16q- syndrome. Severe failure to thrive due to emesis and diarrhea were also observed. High resolution banding methods showed that the chromosome constitution of the patient was 46,XX,del(16)(q22.1q22.3). This suggests that 16q22 is critical for the syndrome.

Chromosome Deletion↗
PubMed1992

High serum IL-6 level reflects susceptible status of the host to endotoxin and IL-1/tumor necrosis factor.

Patients with high level of serum endotoxin did not necessarily develop into lethal shock, whereas some patients died of septic shock even when their serum endotoxin levels were low. These results indicate that limiting factor which determines the host to be endotoxin shock principally depends on the host susceptibility to endotoxin instead of serum endotoxin level. To understand this susceptible status of the host to endotoxin, we used Propionibacterium acnes primed mouse endotoxin shock model. We found that P. acnes-primed mice responded to low dose of LPS by enhanced production of IL-1 and TNF. And such mice were highly susceptible to the lethal shock inducing effect of IL-1 and/or TNF, which also induced high level of serum IL-6 in these mice. Therefore, measurement of serum IL-6 level provides us with the information of the preceding exposure of the host to either LPS or IL-1 and/or TNF and the highly susceptible status of the host to these stimuli. Based on these results obtained from animal model, we investigated the relationship between serum IL-6 levels and serum endotoxin levels in the patients with malignant hematologic disorders. We found that these patients fell into two groups; an endotoxin susceptible group, equivalent to P. acnes-primed mice, showing high level of serum IL-6 with low level of serum endotoxin, and a nonendotoxin susceptible group, equivalent to P. acnes-nonprimed mice, showing low or undetectable level of serum IL-6 with high level of serum endotoxin. We propose that the measurement of serum IL-6 level in the patients positive for endotoxin is a useful tool in evaluating diagnosis and prognosis of endotoxin shock.

Adolescent↗
PubMed1992

DNA fragmentation in focal cortical freeze injury of rats.

This study examined the appearance of double-strand DNA breaks in rat brain after a focal cortical freeze injury in vivo. DNA fragments of oligonucleosome size appeared 3 h after the injury, and increased in a time-dependent manner. At 24 h, the amount of DNA fragmentation reached a maximum and then declined. When nuclei from freeze-injured brain tissue were incubated with Ca2+ in vitro, increased endonuclease activity, which can cause DNA fragmentation, was found. These findings indicate that the activation of a Ca(2+)-dependent endonuclease may be involved in the evolution of freeze-traumatized brain tissue.

Animals↗
PubMed1992

Role and regulation of interleukin (IL)-2 receptor alpha and beta chains in IL-2-driven B-cell growth.

Substantial proportions of resting B cells constitutively express low levels of IL-2 receptor (IL-2R) alpha and/or beta chains. The expression of these chains is differentially regulated by anti-IgM and IL-2/IL-4. The anti-IgM induces IL-2R alpha chain expression, whereas each of the two cytokines induces IL-2R beta chain expression in a dose-dependent manner. Moreover, IL-2 induces the growth of B cells, when the cells were pretreated with IL-2 or IL-4 for 24 h. The magnitude of this IL-2-driven B-cell growth depends upon the level of IL-2R beta chain expression. Costimulation of the B cells with IL-2 and anti-IgM shifts the dose-response curve, and the cells proliferate at an IL-2 concentration as low as 40 pM. These results indicate that the levels of anti-IgM-induced IL-2R alpha chain and IL-2-induced IL-2R beta chain determine the sensitivity of the cells to IL-2.

Animals↗
PubMed1992

Methylated cytosine level in human liver DNA does not decline in aging process.

In order to ascertain a generality of the age-dependent decrease in DNA methylation level among different mammalian species, methylated cytosine contents in human liver and spleen DNA at different ages have been determined using high performance liquid chromatography (HPLC). Unexpectedly, the liver DNA revealed no appreciable decline with age while the spleen DNA showed a slight reduction. It indicates that a decrease of methylation level in genomic DNA is not a common denominator of age-related changes in mammals.

Adolescent↗
PubMed1992

Immunoaffinity purification and cDNA cloning of human platelet prostaglandin endoperoxide synthase (cyclooxygenase).

The cDNA for prostaglandin endoperoxide synthase (cyclooxygenase) was cloned from human platelets by the polymerase chain reaction amplification method, and the primary structure of the enzyme was deduced from the nucleotide sequence. The enzyme was composed of 599 amino acids including 23-amino acid signal sequence, and the calculated molecular weight of the mature protein was 65,995. The enzyme was immunoaffinity-purified from human platelets. The N-terminal amino acid sequence determined by Edman degradation was Ala-Asp-Pro-Gly-Ala-Pro-Thr-Pro-, and the result confirmed the primary structure of the enzyme, which was deduced from the cDNA sequence.

Acetylation↗
PubMed1992

Metabolic changes of glioma following chemotherapy: an experimental study using four PET tracers.

To shed light on the metabolic changes in glioma following therapy, uptake changes among 18F-fluoro-2'-deoxyuridine (18FUdR), 14C-thymidine (dThd), 14C-methionine (Met) and 3H-deoxyglucose (DG) in glioma model after chemotherapy were studied, as a means for interpreting clinical PET results, together with the changes in the bromodeoxyuridine (BUdR) labeling index. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(-2chloroethyl)-3-nitro sourea hydrochloride (ACNU) was administered intraperitoneally in the tumor-bearing rats and uptake of the tracers or BUdR labeling index in tumor tissue were measured. The metabolic response following chemotherapy was a sharp fall immediately for 14C-dThd and 18FUdR and a moderate fall for 14C-Met whereas there was a fall in 3H-DG from 1 week after chemotherapy. The changes of BUdR labeling index paralleled that in the uptake for dThd and FUdR. These result indicate that PET scans using a variety of tracers in conjunction could be used for clinical diagnosis and evaluation of therapy in glioma cases. 18FUdR is a promising tracer of nucleic acid metabolism to evaluate the proliferative potential of brain gliomas.

Animals↗
PubMed1992

Dynamic study of methionine uptake in glioma using positron emission tomography.

In order to evaluate the methionine uptake of a glioma with positron emission tomography (PET), the kinetics of carbon-11 methionine was investigated in 11 patients by measuring the free 11C-methionine in plasma as an input function following intravenous administration. When the mean clearance curve of free 11C-methionine in plasma instead of individual 11C-methionine clearance curves was used, mean differences in uptake rate and distribution volume were 4.0% and 4.6% respectively. By applying the mean clearance curve of free 11C-methionine in 18 glioma patients, significant differences in 11C-methionine uptake rate and distribution volume were found according to pathological grading. For the accurate evaluation of the metabolism of 11C-methionine, it is therefore preferable that the actual level of free 11C-methionine in the plasma be measured, especially for the follow-up of individual cases. The study also demonstrated that the mean clearance curve of 11C-methionine in plasma might be employed as an input curve for calculating the uptake rate and distribution volume with small errors.

Adult↗
PubMed1992

Angiographic findings of ischemic stroke in children.

A cooperative study was undertaken in the Tohoku district of Japan to investigate the relatively rare phenomenon of cerebral infarction in children. The purpose of the present paper is to describe the cerebral angiographic findings in 48 children whose ischemic lesions were confirmed by CT scan. The majority of lesions were considered to be idiopathic. The areas of cerebral infarction appearing in the CT scans were located in the territory of the middle cerebral artery including the basal ganglia. Angiographical abnormalities were observed in 40 patients (83%). The majority occurred in the supraclinoid portion of the internal carotid artery and in the cisternal portion of the middle and anterior cerebral arteries. Multiple lesions, such as in the C1, A1, and M1 or the C1, M1, and M2 segments were observed in 22 cases. These lesions generally appeared in continuation; no bilateral intracranial lesions were observed. Repeated angiography was performed in 22 cases, and in 55% of these some recovery of the lesions was seen.

Cerebral Angiography↗
PubMed1992

Cerebral blood flow and oxygen metabolism in infants with hydrocephalus.

In this study, regional cerebral blood flow (rCBF) and the cerebral metabolic rate of oxygen (rCMRO2) were measured using positron emission tomography (PET) with oxygen-15 radiopharmaceuticals to clarify the pathophysiology of ventriculomegaly in the developing brain. Four hydrocephalic infants without severe neurological deficit were studied. Hypoperfusion was observed in the frontal, parietal, and visual association cortices which surrounded dilated anterior or posterior horns of the lateral ventricle. Lower rCMRO2 values than adult rates were observed in all cases. In the infants with markedly enlarged anterior or posterior horns, the surrounding cortices showed relatively lower rCMRO2 values with the fall of rCBF. Postoperative studies were performed in two infants. rCMRO2 increased in every region after ventriculoperitoneal shunting, but little change was observed in rCBF. These results indicate that metabolic deterioration occurs in the developing brain with hydrocephalus.

Blood Volume↗
PubMed1992

Attempts to induce immune-mediated cerebral arterial injury for an experimental model of moyamoya disease.

To examine the possible role of immune complex-mediated reactions in moyamoya disease, a novel experimental system using a serum sickness vasculitis model combined with intracisternal administration of antibodies or antigens was developed. Twenty-eight male Japanese white rabbits were divided into four experimental groups. Group I was treated twice with intravenous injections of heterologous serum. In group II, intracisternal administration of antibodies or antigens was combined with the second injection of serum. Group III received a single intravenous injection of antigens simultaneously with intracisternal administration of antibodies. Group IV was a technical control group. Cerebral arteritis, although likely in the initial process, was induced only in groups II and III. This study suggests that the cerebral arteries rarely develop arteritis in a serum sickness model alone. The cerebral arteries may require additional intracisternal administration of antibodies or antigens to induce in situ deposition of immune complexes around them.

Animals↗
PubMed1992

Congenital cerebral venous dysgenesis. Decreased cerebral blood flow in deep cerebral regions revealed by SPECT.

This report describes a rare case of primary cerebral venous dysgenesis in a 3-year-old child with development retardation. Angiography resulted in nonvisualization not only of deep cerebral veins but also of superficial cerebral veins. In computed tomography and in magnetic resonance imaging the collateral venous circulation appeared as a strange configuration in the pineal region. Single photon emission computed tomography using N-isopropyl-p-[I-123]-iodoamphetamine revealed decreased regional cerebral blood flow in the basal ganglia and thalamus, but cerebral infarction was not detected in the area. These features indicate that in this case, dysgenesis of deep cerebral veins, which probably occurred during prenatal life, had caused hypoperfusion in the deep cerebral regions.

Carotid Arteries↗
PubMed1992

A case of Rathke's cleft cyst within a pituitary adenoma presenting with acromegaly--do "transitional cell tumors of the pituitary gland" really exist?

A case of multiple large Rathke's cleft cyst within a pituitary adenoma presenting with acromegaly is reported. Rathke's cleft cyst within a pituitary adenoma is rare condition, and this is the first report of such a case presenting with acromegaly. An electron microscopic and an immunohistochemical analysis proved that the cyst within the pituitary adenoma of this case differs from cysts found in the embryonic stage of the pituitary gland.

Acromegaly↗
PubMed1992

The relationship between c-myc protein expression, the bromodeoxyuridine labeling index and the biological behavior of pituitary adenomas.

To clarify the relationship between the percentage of c-myc protein-labeled cells, the bromodeoxyuridine (BrdUrd) labeling index (LI) and clinical malignancy in pituitary adenomas, we studied 31 cases of pituitary adenomas. Tumor invasiveness, recurrence, tumor size and the length of illness were evaluated from operative findings, magnetic resonance imaging findings, and the clinical course. Each pituitary adenoma was scored to represent the degree of clinical malignancy. An hour before excision of the tumor, we administered BrdUrd intravenously. Surgical materials were fixed in 70% alcohol and embedded in paraffin. Both hematoxylin and eosin staining and immunohistochemical staining were performed using a monoclonal antibody for both anti-BrdUrd and anti-c-myc protein. Among pituitary adenomas, there was a significantly low percentage of c-myc protein-labeled cells in cases with acromegaly. The percentage of c-myc protein-labeled cells in the pituitary adenomas tended to increase with increase with the total scores of clinical malignancy. The BrdUrd LI was lower than 1% in almost all cases of pituitary adenomas, and it showed no correlation with their clinical malignancy. In conclusion, determination of the percentage of c-myc protein-labeled cells in pituitary adenomas proved to be useful for evaluating their clinical malignancy.

Adenoma↗