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Biomedical subjects

M Ishihara

Publications and source records attributed to M Ishihara.

At least 127 records · Page 7Linked to original sources

CD8+ T lymphocyte counts as an adjunctive predictor of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

We encountered a case of cytomegalovirus (CMV) retinitis with spontaneous regression in association with an increased number of CD8+ but not CD4+ T lymphocytes in a patient with acquired immunodeficiency syndrome (AIDS). Thus, we examined the number of CD4 and CD8 counts at the diagnosis of CMV retinitis and compared with those of Pneumocystis carinii pneumonia (PCP). All 21 patients with a confirmed diagnosis of PCP (22 episodes) and 14 CMV retinitis patients were included in this study. Although PCP occurred after depletion of CD4 count to below 200/microl, CD8 count at that time varied widely and remained normal in some patients (median: 276.5/microl, range: 133-900/microl). In contrast, as CMV retinitis occurred after further depletion of CD4 count to below 50/microl, CD8 count decreased to below 500/microl (median: 238/microl, range: 43-448/microl) (p<0.05; PCP vs CMV retinitis). The values of the sensitivity and specificity for CMV retinitis obtained at the cutoff point of either 400/microl in CD8 count and 50/microl in CD4 count were similar. When these two cutoff points were combined, the positive predictive value was 46%. Monitoring of CD8 count may prove valuable as an additional predictor of CMV retinitis in patients with AIDS after CD4 depletion.

AIDS-Related Opportunistic Infections↗

[Practical localization of the central sulcus using a video display during surgery by cortical somatosensory evoked potentials and how to discern precentral P20 and central P25].

In patients with lesions around the central sulcus, cortical surface somatosensory evoked potentials (SEPs) have been applied for the purpose of localization of the central sulcus based on the polarity inversion of postcentral N20 to precentral P20 across the central sulcus. We have intraoperatively monitored SEPs to infer the location of the central sulcus in 16 cases since December 1988. Intraoperative localization of the central sulcus has been most useful in patients with frontal lobe gliomas in which the localization of the central sulcus enables the surgeon to extensively resect tumor without postoperative motor weakness. The localization of the central sulcus, however, might be misjudged by using the polarity inversion criterion alone, because central P25 following N20 and P20 complicates SEP waveforms. It is significant that P25, which is recorded also posterior to the central sulcus, is discerned from the precentral P20. In order to solve this matter, we regarded only the positivity in SEP waveforms having the identical peak latency to that of N20 as the precentral P20. Positive potentials having a later peak latency than that of N20 are the superposition of P20 and P25, and might also be recorded posterior to the central sulcus. For the observation of the polarity inversion of N20 to P20 across the central sulcus, a multi-channel SEP should be recorded using a sheet of silicone rubber embedded in a 16-electrode array consisting of a 4 by 4 grid. We projected the exposed cortical surface on the video display through the microscope apparatus and marked the locations of the recording electrodes on the video display. This enabled the location of the recording electrodes to correspond easily and precisely to the cortical surface. Our reliable and simple method of intraoperative localization of the central sulcus by cortical SEPs monitoring is presented in a practical case.

Adolescent↗

[Evaluation of three-dimensional CT angiography (3D-CTA) for the diagnosis of cerebral vasospasm].

We evaluated the usefulness of three-dimensional CT angiography (3D-CTA) for the diagnosis of cerebral vasospasm following subarachnoid hemorrhage (SAH). Eleven patients with SAH who were suspected of having cerebral vasospasm on the basis of their clinical symptoms were examined by 3D-CTA with a spiral CT scanner after an intravenous bolus administration of contrast medium. 3D-CTA revealed vasospastic changes of the cerebral vessels in eight patients. Conventional angiography was performed in six patients immediately after the 3D-CTA examination, and demonstrated the cerebral vasospasm. In eight patients, a second 3D-CTA was performed with the same technique one week after the first 3D-CTA examination. The second 3D-CTA showed the cerebral vessels without vasospastic change. In conclusion, 3D-CTA is a promising, minimally invasive strategy for the assessment of cerebral vasospasm.

Cerebral Angiography↗

[Histological findings of specimens obtained by directional coronary atherectomy from patients with acute myocardial infarction].

The histological characteristics of acute myocardial infarction were examined in specimens obtained from infarct-related coronary artery lesions (20 left anterior descending artery, 2 left circumflex artery, 8 right coronary artery) in 30 patients with initial acute myocardial infarction who underwent directional coronary atherectomy following intracoronary thrombolysis within 6 hours after the onset of chest pain. Resected tissues were fixed in 10% buffered formalin and embedded in paraffin, and the 4 microns-thick paraffin sections were stained with hematoxylin-eosin and examined by light microscopy. Thrombus and/ or intramural hemorrhage were present in all samples. There were high incidences of cholesterol cleft in 19 (63%), foam cell in 21 (70%), calcium deposit in 19 (63%) and intimal proliferation in 16 (53%). These data suggest that thrombus and/or intramural hemorrhage are important in the onset of acute myocardial infarction.

Aged↗

[The usefulness and the problems of attenuation correction using simultaneous transmission and emission data acquisition method: studies on normal volunteers and phantom].

Attenuation correction using simultaneous transmission data (TCT) and emission data (ECT) acquisition method was applied to 201Tl myocardial SPECT with ten normal adults and the phantom in order to validate the efficacy of attenuation correction using this method. Normal adults study demonstrated improved 201Tl accumulation to the septal wall and the posterior wall of the left ventricle and relative decreased activities in the lateral wall with attenuation correction (p < 0.05: paired t-test). The counts of the posterior wall were however, significantly higher than those of the anterior wall and the lateral wall (p < 0.05: unpaired t-test). Moreover, relative low uptake of the apex was enhanced using attenuation correction. Static phantom studies revealed the self scatter from high 201Tl uptake organs such as the liver and the stomach pushed up the activities in the septal wall and the posterior wall. Cardiac dynamic phantom studies showed partial volume effect due to cardiac motion contributed to under-correction of the apex, which might be overcome using gated SPECT. Although simultaneous TCT and ECT acquisition was conceived of the advantageous method for attenuation correction, miss-correction of the special myocardial segments should be taken into account in assessment of attenuation correction compensated images.

Adult↗

[Assessment of left ventricular systolic function derived from ECG-gated myocardial SPECT with 99mTc-tetrofosmin: automatic determination of LV epi- and endocardial surface].

Non-invasive assessment of ischemic heart disease requires information of both LV function and myocardial perfusion. Recently, ECG-gated myocardial SPECT with technetium-labeled radiopharma-ceuticals can provide both of them. Gated myocardial SPECT were performed in thirty-three patients with cardiac disease using a two-headed rotating gamma camera system (ADAC; VERTEX), 30-60 minutes after resting injection of 555-740 MBq of 99mTc-Tetrofosmin. Then, the SPECT data were used to determine the LV epi- and endocardial surface, and LV volume for measurement of LVEF was calculated automatically. This entire computational process required only 210 seconds per 16 frame study. Interobserver agreement of EF values obtained from gated SPECT was excellent (r = 0.996, n = 10, p < 0.01). LVEFs obtained from gated SPECT showed good correlation to those calculated from radionuclide ventriculography (MUGA) (r = 0.91, p < 0.01). In conclusion, this automatic method using gated myocardial SPECT data was considered to be useful for assessment of LV function with reproducibility.

Aged↗

DNA damage-induced apoptosis and Ice gene induction in mitogenically activated T lymphocytes require IRF-1.

Lymphocytes are highly sensitive to DNA damage-induced apoptosis. In thymocytes, the tumor suppressor p53 has been shown to be required for this type of apoptosis. However an as yet unknown, p53-independent pathway(s) appears to mediate the same event in mitogenically activated mature T lymphocytes. By using mice with a null mutation in the IRF-1 gene, we revealed that DNA damage-induced apoptosis in the latter cell type is dependent on the anti-oncogenic transcription factor interferon regulatory factor-1 (IRF-1). Thus two different anti-oncogenic transcription factors, p53 and IRF-1, are required for distinct apoptotic pathways in T lymphocytes. Furthermore, we found that mitogen induction of the interleukin-1 beta-converting enzyme (Ice) gene, a mammalian homolog of the Caenorhabditis elegans cell death gene ced-3, is also IRF-1-dependent. An IRF-1 binding sequence was identified in the 5' flanking region of the Ice gene. In addition, ectopic overexpression of IRF-1 results in the activation of the endogenous Ice gene and enhances the sensitivity of cells to radiation-induced apoptosis. Thus, induction of Ice gene may be involved in IRF-1 dependent DNA damage-induced apoptosis in activated mature T lymphocytes.

Animals↗

[Assessment of cerebral circulation using echo planar imaging--basic analysis in quantitating the mean transit time, cerebral blood flow, and cerebral blood volume].

The mean transit time (MTT), cerebral blood flow (CBF) and cerebral blood volume (CBV) using echo planar imaging (EPI) in 22 aged volunteers were measured based on moment analysis and gamma variate method. The first peak of signal intensity curve (p delta R2.) and the area under the curve after the first peak (AUC) were calculated according to the height over area method, as a convenient quantification. Then, MTT, CBF, and CBV were compared with AUC/p delta R2, p delta R2, and AUC, respectively. There was a good correlation between each other parameter (r = 0.67 - 0.92, every p < 0.001). The slow upward slope and the low peak height, however, caused a larger error between each other parameter.

Blood Flow Velocity↗

[Assessment of regional microcirculatory changes by EPI perfusion studies in patients with multiple lacunar infarction].

The aim of this report is to assess regional cerebral microcirculatory changes by EPI perfusion study in patients with multiple lacunar infarction(MLI). Especially, we focused on the parameter(rCBV, MTT, rCBF) changes in the white matter and on the relationship between these changes in the gray and white matter. Twenty MLI patients(mean age 72 +/- 15 years) and 10 age-similar normal controls (mean age 65 +/- 12 years) were examined. As a result, the MLI patients demonstrated an insignificant rCBF reduction due to the rCBV elevation in the gray matter and a moderate rCBF reduction with less rCBV elevation in the white matter. These results show a difference in the vascular reserve between the gray and white matter, and insufficiency of the vascular reserve in MLI's white matter.

Aged↗

[Cooperative multicentre study on posttraumatic epilepsy].

A multicentre cooperative prospective study have been conducted to investigate the factors influencing posttraumatic epilepsy (PTE) and to evaluate the prophylactic effect of anticonvulsants. Since April 1994, patients with head injury have been observed following our protocol as follows; anticonvulsants are administered only to the patients with brain parenchymal injury for one month just after head trauma and no anticonvulsants are administered after one month after trauma to any patients except those with posttraumatic epilepsy (PTE). Brain parenchymal injury included traumatic subarachnoid hemorrhage, acute subdural hematoma, contusion, intracerebral hematoma, and diffuse axonal injury. To April 1996, 635 patients with head injury have been registered and analyzed. During the follow-up period, 14 patients (2.2%) developed PTEs, which had only been observed in patients with brain parenchymal injury. Multiple regression analysis revealed that two factors, early epilepsy and brain parenchymal injury, could contribute to the prediction of PTE. The frequency of PTE in this study was compared with that in our previous retrospective study (Nakamura, 1995), in which anticonvulsants were administered to the patients with head injury. There was no significant difference in the percentage of patients having PTE between the group treated without anticonvulsants in this study and the untreated group in previous retrospective study. Anticonvulsants treatment after head injury was not likely to have a prophylactic effect against the development of PTE.

Adolescent↗

[Local eosinophilia of the nose, the larynx and the trachea in rats sensitized with Japanese cedar pollen].

Eight Brown Norway rats were immunized twice at days 0 and 13 by intraperitneal injections of 10 micrograms Cry j I, one of major allergen to Japanese cedar pollinosis, mixed with 4.5 mg aluminium hydroxide gel. Serum level of Anti-Cry j I IgE antibody was detected by the method of ELISA. Mean value of serum levels of specific IgE to Cry j I in the sensitized rats was significantly higher than that in the non-sensitized five rats (p < 0.01). The grades of eosinophil and lymphocyte accumulation in the nasal mucosa of the sensitized rats were higher than those in the non-sensitized rats respectively (p < 0.05, p < 0.01). In the laryngeal mucosa, the grade of eosinophilia in the sensitized rats was higher than that in the control (p < 0.01), but no significant differences of lymphocyte accumulation in the larynx between the two groups were found. Only a small number of eosinophil and lymphocyte accumulations in the trachea of the both groups were observed and no significant differences of the grade of inflammatory cells accumulation between the two groups were found. According to the results of this fundamental study, allergic laryngitis in Japanese cedar pollinosis might be originated from Japanese cedar pollen.

Animals↗

Effect of zeta potential of cationic liposomes containing cationic cholesterol derivatives on gene transfection.

Cationic liposomes are known to be useful tools for gene transfection. However, the relation between transfection efficiency and physicochemical properties of liposomes has not been well understood. Here, we synthesized eight cationic derivatives of cholesterol which contain a tertiary amino head group with a different spacer arm. Transfection of plasmid pSV2CAT DNA into cells was done by cationic liposomes made of a mixture of dioleoylphosphatidylethanolamine (DOPE) and each cationic cholesterol derivative. At the same time we measured zeta potential of cationic liposomes by laser Doppler spectroscopy. The present results indicated that zeta potentials of cationic liposomes were well related to transfection activity of pSV2CAT DNA. This suggested that zeta potential of cationic liposomes is one of important factors which control gene transfection.

3T3 Cells↗

Time course of impaired coronary flow reserve after reperfusion in patients with acute myocardial infarction.

To evaluate the time course of coronary flow reserve after reperfusion, 14 patients with a first anterior wall acute myocardial infarction who underwent successful coronary angioplasty within 6 hours after symptom onset were studied. After angioplasty, coronary flow reserve of the left anterior descending artery was measured with a coronary Doppler guidewire and intravenous dipyridamole (0.56 mg/kg over 4 minutes). Measurements were repeated at predischarge (16 +/- 3 days, n = 12) and at follow-up (6 +/- 3 months, n = 9). Patients with restenosis at the time of repeat catheterization were excluded. An additional 13 patients with normal angiograms served as reference patients. Coronary flow reserve was 1.33 +/- 0.29 after angioplasty. It increased to 1.88 +/- 0.36 at predischarge (p <0.01) and further to 2.34 +/- 0.38 at follow-up (p <0.01 vs after angioplasty and at predischarge, respectively). However, compared with reference patients (3.15 +/- 0.48), coronary flow reserve was significantly reduced in the infarct patients even at follow-up (p <0.01). In infarct patients, the infarct region wall motion was initially -3.86 +/- 0.67 SD/chord. It significantly improved to -2.07 +/- 1.04 SD/chord at predischarge (p <0.01) and to -1.67 +/- 1.43 SD/chord at follow-up (p <0.01). However, there was no significant relation between coronary flow reserve and region wall motion after angioplasty (r = 0.10), at predischarge (r = 0.35), and at follow-up (r = 0.28). Thus, coronary flow reserve is severely impaired early after reperfusion. Coronary flow reserve improves over 2 weeks, but the impairment persists at 6 months after acute myocardial infarction. The impairment of coronary flow reserve cannot be predicted by left ventricular function. Small sample size is a potential limitation of this study, and a larger study should be performed to confirm these findings.

Aged↗

Limited proteolysis by chymotrypsin of midkine and inhibition by heparin binding.

When digested with a low concentration of chymotrypsin, midkine (MK) underwent limited proteolysis and produced two fragments with Mr of 11,000 and 6,000 Da. The cleavage site was identified as on the carboxyl side of Phe55. This limited proteolysis was specifically inhibited by heparin, but not by other glycosaminoglycans. Using various heparin-derived oligosaccharides with different chain lengths or chemically desulfated heparin derivatives, it was shown that a minimum of 6 monosaccharide units was necessary for the inhibition, and that sulfonyl groups of the heparin disaccharide unit were required for inhibition. The present study showed that MK consists of two domains, N- and C-domains, and that Phe55 localized to the hinge region is exposed on the surface of the molecule. It was also suggested that the N-domain may function as a stabilizing domain against proteolytic degradation of the C-domain in the intact molecule.

Amino Acid Sequence↗

HLA-C genotyping of patient with Behçet's disease in the Japanese population.

Behçet's disease has been known to be strongly associated with a particular HLA-B allele, B51. To address the possibility that the HLA-C gene, which is closely linked to HLA-B but has been poorly defined for allo-antigen specificity by the serologic method is involved in the susceptibility to Behçet's disease, HLA-C genotyping was performed for 90 Japanese Behçet's disease patients by the PCR-SSP method. The frequencies of HLA-Cw*14 and -Cw*15 were significantly higher in the patient with Behçet's disease as compared to the controls (48.9% vs. 24.0%, p = 0.0005, and 17.8% vs. 7.3%, p = 0.0434, respectively). On the other hand, the frequencies of HLA-Cw*0304 and -Cw*01 were significantly decreased in the patient group as compared to the control group (7.8% vs. 25.0%, p = 0.0027, and 23.3% vs. 37.5%, p = 0.0398, respectively). The significantly higher HLA-Cw*14 and -Cw*15 alleles may tightly correlate with the B51 antigen, and hence may have increased as a result of a linkage disequilibrium with B51. Accordingly, the HLA-C allele frequencies were compared for the B51-positive or -negative patients and controls, but there was no HLA-C allele showing a significant difference between these patient and control groups. Conversely, analysis of the HLA-B allelic distribution in association with HLA-Cw*14 revealed that in the healthy controls, B44 and B51 were present at the frequencies of 57.1% and 35.7% of the HLC-Cw*14-positive individuals, respectively. In contrast, in the Cw*14-positive patients the frequency of B44 was merely 14.0% (p = 0.0001) and that of B51 was significantly high, amounting to 82.0% (p = 0.0001). These facts suggest that the pathogenic gene of Behçet's disease is not the HLA-C gene (HLA-Cw*14 and/or HLA-Cw*15) but the HLA-B gene (HLA-B51) itself or a non-HLA gene residing in the centromeric side of the HLA-B gene rather than in the telomeric side around the HLA-C gene. This finding supports our previous mapping result, which located the susceptible gene between the TNF and HLA-B genes.

Alleles↗

Analysis of HLA-DM polymorphisms in sarcoidosis.

Sarcoidosis is a multisystemic granulomatous disorder showing significant increases in the HLA-DRB1*11, *12, *14 and *08 alleles in the Japanese population. To evaluate the role of polymorphism in the DMA and DMB genes in predisposition to sarcoidosis, seventy Japanese patients with sarcoidosis and 95 unrelated healthy controls were analyzed in the third exon polymorphisms within the DMA and DMB genes by the PCR-RFLP method. There were no differences in the distribution of DMA alleles between the patient and control groups. The frequency of DMB*0102 was higher (p < 0.05) and that of DMB*0101 was lower (p < 0.05) in the patients than in the healthy controls. However, this association and negative association could be explained by linkage disequilibrium with the disease-associated DRB1 alleles. The DMA and DMB genes do not primarily confer the susceptibility to sarcoidosis.

Adult↗

Cooperation of the tumour suppressors IRF-1 and p53 in response to DNA damage.

Normally growing cells promptly cease DNA synthesis when exposed to genotoxic stresses, such as radiation, and this cell-cycle arrest prevents the accumulation of mutations. The transcription factor interferon regulatory factor (IRF)-1 is essential for the regulation of the interferon system, inhibits cell growth, and manifests tumour-suppressor activities. Here we show that mouse embryonic fibroblasts (EFs) lacking IRF-1 are deficient in their ability to undergo DNA-damage-induced cell-cycle arrest. A similar phenotype has been observed in EFs lacking the tumour suppressor p53 (refs 8, 9), although the expression of IRF-1 and p53 are independent of one another. Furthermore, we show that transcriptional induction of the gene encoding p21 (WAF1, CIP1), a cell-cycle inhibitor, by gamma-irradiation is dependent on both p53 and IRF-1, and that the p21 promoter is activated, either directly or indirectly, by both in a transient cotransfection assay. These two tumour-suppressor transcription factors therefore converge functionally to regulate the cell cycle through the activation of a common target gene.

Animals↗