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Biomedical subjects

M Sekiya

Publications and source records attributed to M Sekiya.

At least 19 recordsLinked to original sources

Thallium-201 myocardial tomography with intravenous infusion of adenosine triphosphate in diagnosis of coronary artery disease.

OBJECTIVES: The purpose of this study was to evaluate the feasibility, safety and diagnostic accuracy of thallium-201 myocardial tomography with intravenous adenosine triphosphate (ATP) infusion in patients with suspected coronary artery disease. BACKGROUND: Both ATP and adenosine are potent coronary vasodilators with a very short half-life. Several studies have confirmed that the diagnostic accuracy of adenosine thallium-201 scintigraphy is comparable to that with exercise. However, a high incidence of side effects, including atrioventricular (AV) block, has also been reported. Because the appropriate infusion rate for ATP has not yet been determined, this agent has not been tested in combination with myocardial scintigraphy. METHODS: The study group included 253 consecutive patients who underwent thallium-201 myocardial tomography with ATP infusion (0.16 mg/kg body weight per min for 5 min). The occurrence of adverse effects was carefully monitored. Of the 120 patients with coronary angiography, 76 had significant coronary artery disease. Tomographic images were assessed visually and by computer-quantified polar maps, and they were compared with the results of coronary angiography. RESULTS: Although 56% of the patients had some adverse effects, they were transient and mild. In all patients, the ATP infusion protocol could be completed, and no patient required aminophylline; AV block occurred in only 2% of the patients. The sensitivity and specificity were 88% and 80%, respectively, by visual analysis and 91% and 86%, respectively, by computer quantification. CONCLUSIONS: Thallium tomography with ATP is feasible and has a diagnostic value similar to that with adenosine for detecting coronary artery disease. In addition, it may have fewer side effects than adenosine myocardial tomography.

Adenosine Triphosphate

IL-2-induced gene expression of protein-tyrosine phosphatase LC-PTP requires acidic and serine-rich regions within IL-2 receptor beta chain.

A protein-tyrosine phosphatase LC-PTP is preferentially expressed in hematopoietic cells and is an early response gene in lymphokine stimulated cells. Here, we found the LC-PTP mRNA induction by IL-2 was markedly inhibited by several tyrosine kinase inhibitors. The induction required both the acidic and serine-rich regions of the IL-2 receptor beta chain (IL-2R beta) in mouse IL-3-dependent pro-B BAF-B03 transfectants. This is strikingly different from the induction of c-myc gene expression, which requires the serine-rich region alone. In addition, overexpression of activated-Lck or -Raf kinases resulted in augmented LC-PTP mRNA expression in myeloid cell line 32D transfectants. Considering the previous findings that the acidic region of the IL-2R beta is responsible for association with Lck and activation of Raf kinase, IL-2-induced expression of LC-PTP mRNA may be primarily transduced through a Lck-Raf mediated signaling pathway.

Animals

[Normal-sized ovary carcinoma syndrome: histopathological analysis of 14 cases].

Fourteen cases of "normal-sized ovary carcinoma syndrome" (diffuse metastatic malignant disease of the abdominal cavity of the female, with normal-sized ovaries, with no origin assigned definitively by intraoperative or preoperative evaluation, Feuer et al., 1989) were analyzed histologically, histochemically, immunohistochemically and ultrastructurally. Through these studies, 14 cases were divided into 11 primary peritoneal tumors (4 diffuse malignant mesotheliomas and 7 serous surface papillary carcinomas) and 3 metastatic peritoneal tumors (2 ovarian tumors and 1 appendicular tumor). To distinguish serous surface papillary carcinomas from epithelioid diffuse malignant mesotheliomas, examinations such as hyaluronidase digestion test, electron microscopy, and immunohistochemical studies using antibodies for Ber-EP4 and Vimentin were found to be useful. In order to achieve an accurate prognosis of normal-sized ovary carcinoma syndrome, it seems necessary for us to accumulate more information on this syndrome.

Carcinoma, Papillary

Downregulation of Wilms' tumor gene (wt1) during myelomonocytic differentiation in HL60 cells.

The putative Wilms' tumor-suppressor gene (wt1) encodes a zinc finger DNA binding protein that functions as a transcription repressor. The wt1 gene expression corresponds to kidney development, suggesting a role for this gene in nephroblast differentiation. Here we show that wt1 mRNA expression was downregulated during terminal differentiation of promyelocytic HL60 cells. When HL60 cells were induced to differentiate to granulocytes by dimethyl sulfoxide (DMSO) or retinoic acid (RA), a marked downregulation in the levels of wt1 transcripts was found. The wt1 transcripts were also downregulated in HL60 cells during differentiation to monocytes by vitamin D3 or 12-o-tetradecanoyl-phorbol-13-acetate. Nuclear run-on transcription studies showed the transcriptional rate of wt1 gene was not significantly altered during DMSO-induced granulocytic differentiation, suggesting the downregulation was mostly caused by posttranscriptional modification. Importantly, wt1 transcripts were not significantly altered in K562 cells by treatments with DMSO or RA, which do not induce differentiation of K562 cells. These findings suggest that wt1 gene expression may be downregulated as a differentiation-linked event in HL60 cells.

Base Sequence

Induction of protein-tyrosine phosphatase LC-PTP by IL-2 in human T cells. LC-PTP is an early response gene.

Tyrosine phosphorylation has been implicated in interleukin 2 (IL-2)-induced growth signaling and the phosphorylation levels are regulated by the balance of tyrosine kinase and tyrosine phosphatase activities. Here, we demonstrate the rapid activation of a leukocyte tyrosine phosphatase LC-PTP (HePTP) gene expression by IL-2 in an IL-2 dependent human T cell ILT-Mat. Accumulation of LC-PTP mRNA appeared at 1 h and peaked at 6 h after IL-2 stimulation, simultaneous with the G1 to early S phase, and the induction of LC-PTP mRNA did not require protein synthesis. LC-PTP protein increased approximately 6-fold at 8 h after IL-2 stimulation. Nuclear run-on assays showed that the induction of LC-PTP mRNA expression is mostly due to transcriptional activation. These data suggest that LC-PTP is an early response gene and its protein seems to be a crucial molecule which regulates the tyrosine phosphorylation level during T cell proliferation.

Enzyme Induction

Gastric emptying-limited oral absorption of alpha-linolenic acid administered as a milk fat-globule membrane (MFGM) emulsion in rats.

As a study to assess the potential application of milk fat-globule membrane (MFGM), which is of natural origin and expected to be a safer alternative to synthetic emulsifiers, to pharmaceutical dosage forms, the oral absorption of alpha-linolenic acid was evaluated by the analysis of gastrointestinal disposition after oral administration as an MFGM emulsion to rats. A linear model incorporated with first-order gastric emptying followed by first-order intestinal absorption was fitted to the data of the remaining fraction of alpha-linolenic acid versus time profiles for the stomach and small intestine to estimate the rate constants of gastric emptying (kg) and intestinal absorption (ka). The ka (0.045 min-1) was about 4 times larger than the kg (0.011 min-1). The kg was comparable to the apparent oral absorption rate constant estimated by the pharmacokinetic analysis of plasma concentration data. These results suggest that the oral absorption of alpha-linolenic acid administered as MFGM emulsion is gastric emptying-limited and, hence, any change in the intestinal absorption process would only modestly affect its oral absorption.

Animals

Evaluation of milk fat-globule membrane (MFGM) emulsion for oral administration: absorption of alpha-linolenic acid in rats and the effect of emulsion droplet size.

The performance of milk fat-globule membrane (MFGM) emulsion as an oral dosage form was evaluated in rats using [14C]alpha-linolenic acid as a lipophilic model solute. For emulsions prepared by homogenization alone, the area under the plasma concentration versus time curve (AUC) after oral administration tended to be larger for MFGM emulsion, 35.0 +/- 2.5 micrograms eq.h/ml (mean +/- S.E., n = 3), than for Tween 80 emulsion, 28.5 +/- 0.6 micrograms eq.h/ml at p < 0.1, though the peak plasma concentration (Cmax) and the time required to reach Cmax (Tmax) were not significantly different. The absorption in the intestinal loop was not significantly different between the two emulsions, either. Thus, MFGM emulsion, compared with Tween 80 emulsion, did not show an obvious advantage or enhancement in the oral and intestinal absorption of alpha-linolenic acid, except for a slight increase in AUC. However, MFGM could be a good alternative to a synthetic emulsifier for oral use, considering that it is of natural origin and may be safer. In addition, it was shown that the AUC, as well as the absorption in the intestinal loop, was decreased for a MFGM emulsion in which the droplet size was reduced by sonication, presumably because of the observed decrease in alpha-linolenic acid concentration in the water phase, which was assumed to be the result of an increased distribution of alpha-linolenic acid, due to its amphipathic nature, to the increased oil-water interface.

Administration, Oral

Systolic anterior motion of the mitral valve associated with acute myocardial infarction in a 62-year-old patient.

A 62-year-old patient was admitted to our hospital for treatment of early gastric cancer. After total gastrectomy, he suffered from anteroseptal myocardial infarction. Systolic anterior motion of the mitral valve which was not observed before surgery was observed during the acute phase of myocardial infarction and completely disappeared 3 weeks after the onset of myocardial infarction. Systolic anterior motion of the mitral valve in this patient may have been caused by changes in left ventricular wall motion during the acute phase of myocardial infarction.

Echocardiography

[A correlative study of the aluminum content and aging changes of the brain in non-demented elderly subjects].

The interrelation of the aluminum content and aging change of the nerve cells was studied with special reference to the neurofibrillary tangle (NFT) and occurrence of senile plaque (SP), in 15 autopsied brains (cerebrum) of non-demented elderly subjects varying in age from 75 to 101 years old and 10 cases of non-demented non-elderly adult subjects. 1) In the brain of non-demented non-elderly adult subjects, the aluminum content of the hippocampus was 14.4 +/- 1.39 ppb and that of the cortex of the frontal lobe was 20.4 +/- 2.54 ppb. In the brain of the non-demented elderly subjects, the aluminum content of the hippocampus was 401.7 +/- 60.05 ppb and that of the cortex of the frontal lobe was 373.29 +/- 72.35 ppb. Comparison of the two groups showed obviously higher levels in the latter group, being 28 times in the hippocampus and 19 times in the cortex of the frontal lobe. 2) The histochemical demonstration of the aluminum localization by the Morin method disclosed the positive fluorescence reaction along the part of the disintegrating neurofibrillary tangle and amyloid core in the senile plaques of non-demented elderly subjects. In the normal brain tissue, positive fluorescence reaction was observed in the wall of the capillary vessels of the blood brain barrier, perivascular glial supporting tissues, the nuclei of the astrocytes and nuclei, nucleoli of the nerve cells partially. No fluorescence reaction was observed in the non-demented adult subjects. 3) Morphologically, the appearance of the neurofibrillary tangle was noted in some cases of non-demented elderly group with higher aluminum levels. Classical and diffuse type senile plaques were dispersed in the 1st to 4th zone of the cortex of the frontal lobe. However, diffuse type senile plaques in the hippocampus appeared to a lesser extent. Neurofibrillary tangles were slightly noted in the cortex of the frontal lobe, however marked increase was confirmed in the CA1 to CA3 zones of the hippocampus. Ultrastructurally, paired helical filaments (PHF) were noted in the neurofibrillary tangle constituent and the increase of amyloid fibrils in senile plaques was confirmed. In this study, high levels of the aluminum content of the brain were confirmed in the non-demented elderly subjects. Moreover, the histochemical demonstration of aluminum localization by the Morin method disclosed a positive fluorescence reaction along the sites of neurofibrillary tangles and amyloid core in the senile plaques of non-demented elderly subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged

[Complete remission during administration of rhG-CSF in acute myeloblastic leukemia with pneumonia].

A 54-year-old man was admitted with pneumonia and pancytopenia (WBC 400/microliters, RBC 297 x 10(4)/microliters, Hb 10.1g/dl, Plt 5.6 x 10(4)/microliter). Bone marrow aspiration revealed a proliferation of leukemic cells (61.6%) and led the diagnosis of AML (M2). Although no antileukemic agent had been administered previously, the combination therapy of antimicrobials and rhG-CSF for the infection not only improved pneumonia, but also induced a complete remission of AML. The short-term remission was followed by the first relapse of AML, in spite of the continuous administration of rhG-CSF. The abnormal karyotype (47, XY, +8) shown in the chromosomal analysis of the bone marrow cells at admission remained on the first remission. The second complete remission was induced by combination chemotherapy (BHAC-DMP), and the chromosomal analysis at this time showed a normal karyotype. These findings suggested that the first remission of AML in this case was caused mainly by the maturation induction effect of rhG-CSF on the leukemic cells, however, the possibility of the spontaneous remission in this case also remained.

Antineoplastic Combined Chemotherapy Protocols

[c-erbB-2 oncogene product expression in lacrimal gland tumors].

Using a polyclonal antibody to the c-erbB-2 oncogene product (ErbB-2 protein), an immunohistochemical study on the expression of ErbB-2 protein in lacrimal gland tumors was performed. The expression of ErbB-2 protein was observed in 4 (33.3%) of 12 cases of pleomorphic adenoma, but was not in two cases of adenoid cystic carcinoma and one case of normal lacrimal gland. The immunohistochemical reaction was localized in the cell membrane and cytoplasm, and was more intense in the former. There were strongly stained cells in the epithelium of ductal cell lineage and in the solid area, and some of the cells in the myxoid/chondroid areas were weakly stained. The relation ErbB-2 protein with the malignant lacrimal gland tumors in general is not clear, but pleomorphic adenomas of lacrimal gland could have some relation with this protein.

Adult

[Assessment of myocardial viability by thallium-201 reinjection imaging with sublingual nitroglycerin].

Although thallium-201 (201Tl) reinjection imaging improves the detection of myocardial viability compared to standard 3-4-hr redistribution (RD) imaging, it still underestimates the extent of viable myocardium. We examined whether 201Tl reinjection SPECT with sublingual nitroglycerin (NTG) had a higher sensitivity for viability detection than reinjection alone. Eighty patients with coronary artery disease were studied, 38 of them with an old myocardial infarction. At the peak of exercise, 111 MBq 201Tl was injected and the initial and the delayed SPECT images were obtained. Then, all patients were divided randomly into two groups, and in each group, SPECT data were obtained again after the injection of 37 MBq 201Tl with (NTG(+) group) or without 0.6 mg of sublingual NTG (NTG(-) group). Among 50 segments showing fixed defects on the delayed image in the NTG(+) group, 21 (42%) were found to be reversible on the reinjection image, as compared to 16 of 51 (31%) in the NTG(-) group. Twenty-two of 44 (50%) segments showing incomplete RD were found to be reversible in the NTG(+) group, while 17 of 42 (41%) segments in the NTG(-) group. Moreover, the ratio of reversible segments seen in the reinjection images was significantly higher in the collateralized regions of the NTG(+) group than in those of the NTG(-) group (20/26 vs. 14/28, p < 0.05). Thus, 201Tl reinjection SPECT with sublingual NTG improves the detection of ischemic but viable myocardium as compared to SPECT with reinjection alone.

Administration, Sublingual

Selective alpha 1-adrenergic inhibition improves decrease glucose disposal in patients with essential hypertension.

This study evaluated insulin secretion and insulin sensitivity before and after short-term oral administration of doxazosin in patients with essential hypertension. The hypertensive group consisted of 11 nonobese subjects (aged 41.0 +/- 2.5 years (mean +/- SEM), body mass index 24.0 +/- 0.53 kg/m2). The normotensive group consisted of 12 subjects matched to the hypertensive group for age and body mass index. The hypertensive group showed significantly higher concentrations of prestimulated and stimulated plasma insulin and plasma C peptide than normal groups. The insulin-mediated glucose disposal rate during euglycaemic clamp (M-value) was significantly lower in the hypertensive group than in normal controls (7.32 +/- 0.56 vs 8.88 +/- 0.34 mg/kg/min, P < 0.05). After one month of doxazosin treatment blood pressure was significantly reduced (P < 0.05). The short-term administration of doxazosin improved the M-value significantly to 8.60 +/- 0.62 mg/kg/min without a significant change in stimulated plasma C-peptide level. These data show that hypertension is associated with increased insulin secretion and impaired insulin sensitivity. Selective alpha 1-adrenergic inhibition with doxazosin improves the decreased glucose disposal rate associated with hypertension.

Administration, Oral

[Characteristic event-related potentials evoked by somatosensory tasks in a patient with right-left disorientation and finger agnosia].

Event-related brain potentials associated with both somatosensory and auditory detection tasks were recorded from the scalp in a 63-year-old man with finger agnosia and right-left disorientation resulted from cerebral infarction located around the region of the left angular gyrus. In a somatosensory oddball paradigm for discrimination between the right index finger (target, P = 0.2) and the left index finger (non-target, P = 0.8), early cognitive components P100, N140 and processing negativity were observed both in the target responses and non-target responses, however, no P300 component was recorded in both paradigms. In another paradigm to discriminate the index finger (target, P = 0.2) from small finger (non-target, P = 0.8) in the right hand, no P300 was evoked and only processing negativity was recorded both in the target responses and nontarget responses. These phenomena were obtained through characteristic behavior that the patient paid attention to the target stimuli as well as non-target stimuli and mentally counted them without discrimination. In contrast, in an auditory oddball paradigm P300 was clearly demonstrated to target stimuli that the patient correctly could count. The normal appearance of P300 in auditory detection tasks strongly suggests that the neural generator for the P300 was reserved intact. These results indicate that somatosensory information processing might be disturbed at the level of sensory discrimination needed for generation of P300 in our patient. It is also proposed that the neural events for somatosensory discrimination and auditory discrimination would take separate channels each other to reach the common generator of p300 in information processing.

Brain

Structure of the human LC-PTP (HePTP) gene: similarity in genomic organization within protein-tyrosine phosphatase genes.

Recently, various cDNA sequences coding protein-tyrosine phosphatases (PTPs) have been reported and their extensive similarities in the catalytic domains clarified, but knowledge of the structures and organizations of their genes is still limited. In this study, a detailed structure and organization of the human intracellular LC-PTP (also called HePTP) gene is reported. The 13 to 18.5 kb genomic clones encoding human LC-PTP have been isolated. The LC-PTP gene is organized into 11 exons, including the 5'-noncoding first exon and the 3'-noncoding exon. Splicing sites for exons 4 to 10, which encode the conserved catalytic PTP domain, arise almost at the same position as for the CD45 gene. This elucidation of the LC-PTP gene structure provides insight into the domain evolution of intracellular LC-PTP and transmembrane CD45, which may be generated by gene duplications of an ancestral gene.

Amino Acid Sequence

A patient with cardiac amyloidosis presenting a rapid increase in technetium-99m-hydroxymethylene diphosphonate accumulation.

We assessed the changes in cardiac condition in a patient with cardiac amyloidosis, by means of dual nuclei single photon emission computed tomographic (SPECT) images with technetium-99m-hydroxymethylene diphosphonate (99mTc-HMDP) and thallium-201 (201Tl). Dual SPECT showed a marked increase in myocardial 99mTc-HMDP accumulation along with deterioration of symptoms and signs, while 201Tl scintigraphy remained almost unchanged.

Aged

Acetylcholine-induced myocardial ischemia without epicardial coronary artery spasm: a possible vasospasm of small coronary arteries--a case report.

Small-vessel vasospasm has been speculated upon as a possible cause of chest pain in patients with normal-appearing coronary angiograms. In this report, a patient who experienced typical chest pain during acetylcholine testing, which caused ST segment elevation without epicardial coronary spasm, is presented. This finding suggests that small-vessel vasospasm may be involved in the induction of myocardial ischemia in patients with normal epicardial coronary arteries.

Acetylcholine