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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 181 records · Page 10Linked to original sources

Diagnostic potential and pitfalls of ultrasound-guided fine-needle aspiration cytology for breast lesions.

Ultrasound (US)-guided fine-needle aspiration cytology (FNAC) is now widely accepted as a diagnostic procedure for breast lesions. Along with its advantages, US-guided FNAC also has some pitfalls. The recognition of these pitfalls for this procedure is extremely important for the strict management of the disease. We retrospectively investigated the diagnostic potential and pitfalls of US-guided FNAC in the diagnosis of breast lesions. This study consisted of 348 aspirated samples from 274 breast tumors. The rate of sufficient aspirates was 74% after a single aspiration, while sufficient materials were finally obtained from 93% of the tumors by repeated aspirations. The rate was lower in tumors measuring less than 10 mm in diameter (62%), and in sclerosing adenosis (25%). The sensitivity of FNAC was 65%, the specificity was 75%, the border diagnosis rate was 18%, and the positive predictive value was 92%. The false-negative rate was higher in noninvasive carcinoma (45%). The border diagnosis rate was also higher in scirrhous carcinoma (29%). There were also five false-positive cases. Limited to nonpalpable lesions, the sufficient aspirates rate was 70% and the accuracy was 67%.

Adenocarcinoma, Scirrhous↗

Delayed and selective motor neuron death after transient spinal cord ischemia: a role of apoptosis?

OBJECTIVE: The mechanism of spinal cord injury has been thought to be related to tissue ischemia, and spinal motor neuron cells are suggested to be vulnerable to ischemia. We hypothesized that delayed and selective motor neuron death is apoptosis. METHODS: Thirty-seven Japanese domesticated white rabbits weighing 2 to 3 kg were used in this study and were divided into two subgroups: a 15-minute ischemia group and a sham control group. Animals were allowed to recover at ambient temperature and were killed at 8 hours, and 1, 2, 4, and 7 days after reperfusion (n = 3 at each time point). By means of this model, cell damage was histologically analyzed. Detection of ladders of oligonucleosomal DNA fragment was investigated with gel electrophoresis up to 7 days of the reperfusion. Immunocytochemistry, in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining was also performed. RESULTS: After 15 minutes of ischemia, most of the motor neurons showed selective cell death at 7 days of reperfusion. Typical ladders of oligonucleosomal DNA fragments were detected at 2 days of reperfusion. Immunocytochemistry showed in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end staining was detected at 2 days of reperfusion selectively in the nuclei of motor neurons. CONCLUSION: These results suggest that delayed and selective death of the motor neuron cells after transient ischemia may not be necrotic but rather predominantly apoptotic.

Animals↗

Enhancement of heat shock protein expression after transient ischemia in the preconditioned spinal cord of rabbits.

PURPOSE: This investigation was designed to evaluate the mechanism used to acquire a tolerance to spinal ischemia. We investigated inductions of the heat shock protein (HSP) 70 gene and protein in rabbit spinal cord with or without preconditioning. METHODS: Neurologic function, morphologic changes, and inductions of HSP70 messenger RNA (mRNA) and protein were compared in the cases of a 15-minute ischemia 2 days after sham treatment and a 15-minute ischemia 2 days after 10-minute preconditioning. RESULT: HSP70 mRNA was induced at 8 hours of reperfusion after a 15-minute ischemia 2 days after sham treatment. HSP70 protein was induced slightly in selective motor neuron cells at 8 hours of reperfusion, and about 70% of motor neuron cells showed selective cell death after 7 days of reperfusion (p < 0.01). On the other hand, large populations of the motor neuron cells survived at 7 days after the 15-minute ischemia that was applied at 2 days after preconditioning (p < 0.01). HSP70 mRNA was induced persistently as compared with the case of a 15-minute ischemia 2 days after sham treatment. The motor neuron cells strongly produced immunoreactive HSP70 from 8 hours to 2 days. CONCLUSION: Preconditioning with 10-minute ischemia enhanced and prolonged the HSP70 gene expression at both mRNA and protein levels and saved the motor neuron cells from subsequent lethal ischemia. These changes of HSP70 gene expression may play an important role in the acquisition of ischemic tolerance of motor neuron cells in rabbit spinal cord.

Animals↗

Suppression of alloreactivity with gamma delta T-cells: relevance to increased gamma delta T-cells following bone marrow transplantation.

Several reports have shown that an increase in T-cell receptor gamma/delta-positive T-cells (gamma delta T-cells) have been observed following bone marrow transplantation. gamma delta T-cells expanded from peripheral blood mononuclear cells from normal volunteers were used to investigate the function of gamma delta T-cells in vitro. Peripheral blood mononuclear cells were cultured with synthetic ligand of gamma delta T-cells, monoethyl phosphates (MEP), for 7 days. MEP specifically expanded gamma delta T-cells. Expanded gamma delta T-cells from subject "B" were added to an A anti-B or A anti-C mixed lymphocyte culture (MLC) containing responder cells from subject "A" and irradiated stimulator cells from subjects "B" or "C". The cultures were harvested on day 6 and tested for cytotoxicity against stimulator-type Con A blasts. gamma delta T-cells from subject "B" specifically inhibit generation of allospecific cytotoxic T lymphocytes (CTL) in A anti-B MLC. The results indicate that gamma delta T-cells exhibit veto-type suppression of alloreaction. If the current experiments are also applicable in vivo, gamma delta T-cells originating from the donor after bone marrow transplantation may inhibit graft rejection by suppressing recipient anti-donor reactivity. gamma delta T-cells may be involved in the suppression of allogeneic reaction in vivo following allogeneic bone marrow transplantation.

Bone Marrow Transplantation↗

Late-onset unilateral renal dysfunction combined with non-insulin-dependent diabetes mellitus and bronchial asthma following allogeneic bone marrow transplantation for acute lymphoblastic leukemia in a child.

We report a child with T cell acute lymphoblastic leukemia who developed late-onset multiple complications after allogeneic bone marrow transplantation from an HLA-matched sibling. The preparative regimen consisted of total body irradiation (TBI, 12 Gy), splenic irradiation (6 Gy) and cytosine arabinoside (3 g/m2 x 10). Splenic irradiation was added because of persistent splenomegaly in spite of intensive chemotherapy. He developed bronchial asthma 1 1/2 years post transplant. He presented with microhematuria and proteinuria 4 1/2 years post-transplant, which were due to unilateral left renal dysfunction. He developed type II, non-insulin-dependent diabetes mellitus 8 years post-transplant. A biopsy from the left kidney was not compatible with diabetic nephropathy. All these complications appear to be independently related to BMT, particularly TBI and/or splenic irradiation.

Adolescent↗

Amplification of the TCL1 flanking region at 14q32.1 with no TCL1 gene transcription in a patient with peripheral T cell lymphoma.

Cytogenetic and molecular-genetic characteristics in peripheral T cell lymphoma (PTL) have not been well defined, except for those in adult T cell leukemia/lymphoma (ATL/L). Translocations and inversions involving a chromosome band 14q32 were extremely common abnormalities reported in PTL and ATL/L. We studied the involvement of TCL1, a recently isolated gene located in 14q32.1, in tumor tissues from 20 patients with PTL including three with 14q32 translocations by two color fluorescent in situ hybridization (FISH) using two cosmid probes flanking the TCL1 gene. The two cosmid signals were separated in none of them, but much increased in number in one tumor without 14q32 translocation, indicating that the TCL1 genomic region was amplified in this tumor. Reverse transcription-polymerase chain reaction (RT-PCR), however, failed to detect the TCL1 transcript in the tumor. These findings suggest that an oncogene other than TCL1 may be located in 14q32.1, and its amplification may be involved in the neoplastic process of PTL.

Aged↗

Clinical utility of serum levels of eosinophil cationic protein (ECP) for monitoring and predicting clinical course in childhood asthma.

BACKGROUND: The concentration of ECP in serum has been proposed as a marker of airway inflammation in asthma. However, its clinical significance is still to be determined. OBJECTIVES: This study was performed to determine whether concentration of ECP in serum reflects clinical status in asthma and can serve as a predictive parameter. METHODS: Cross-sectional analysis was performed in 28 children with asthma. A total of 91 blood samples was obtained to determine levels of ECP in serum and eosinophil counts. Forced expiratory volume in 1 s was also determined at the time of the sampling. Data were analysed on the basis of asthma symptoms in the 4 weeks before and the 4 weeks after sampling. RESULTS: Serum levels of ECP were significantly lower in patients who had been asymptomatic for 3 or 4 weeks before sampling than in patients who had been symptomatic or asymptomatic for only 1 or 2 weeks. In the former group, serum levels of ECP were higher when patients became symptomatic after sampling than when they remained stable, a finding that suggests that serum levels of ECP may have a predictive value in certain situations. Although the concentration of ECP in serum was not proved to be predictive in the latter symptomatic group, the concentration of ECP was significantly lower when measured again 4 weeks later when the patients' symptoms had resolved. In contrast, levels of ECP were unchanged when patients remained symptomatic, a finding that suggests serum levels of ECP may reflect the clinical response to therapy. CONCLUSIONS: Serum ECP may be a useful marker for monitoring and predicting the clinical course in asthma.

Adolescent↗

Cytokine-enhanced mixed lymphocyte reaction (MLR) in cord blood.

Although in cord blood (CB) transplantation graft-versus-host disease (GVHD) is reported to be less severe, GVHD may occur even in patients with HLA-identical sibling donors. This result shows that HLA typing can not entirely predict GVHD. The standard MLR with CB cells was either normal or slightly reduced compared with adult peripheral blood (PB) cells. We used two manipulations to increase the responses of CB cells to allo-antigens. The first was to treat the stimulator cells with cytokines, and the second to amplify weak proliferative responses by adding exogenous cytokines to MLR cultures (modified MLR). The stimulator cells were treated with both interferon-gamma (IFN-gamma) and IL-4. The responder cells were treated with both IL-2 and tumour necrosis factor-alpha (TNF-alpha). It is still to be determined whether or not this cytokine-enhanced MLR could be a possible predictor of GVHD. However, using these cytokines, 90% of CB could recognize allo-antigens, even if the standard MLR was negative.

Adult↗

Postinfarction left-ventricular aneurysm: regional stress, function, and remodeling after aneurysmectomy.

BACKGROUND: Left-ventricular (LV) aneurysm formation after myocardial infarction (MI) leads to LV remodeling with global and regional cardiac dysfunction. LV aneurysmectomy (LVA) can often improve LV function, but changes of regional wall stress and systolic function in the noninfarcted segment before and after the operation remain poorly understood. The purpose of this study was to assess the effects of LVA on regional stress and systolic function in the noninfarcted region and to examine this procedure's impact on the LV remodeling in patients with LV aneurysm after myocardial infarction (MI). METHODS: Using quantitative left ventriculography and pressure measurements, 11 patients with an anterior LV aneurysm were studied before and 8 months after standard linear repair (LVA group), and 10 patients with an anterior transmural infarction who received coronary artery bypass grafting were also studied (CABG group) in an attempt to separate the effects of aneurysmectomy from the effects of bypass surgery. Regional end-systolic (ESS) and end-diastolic (EDS) stresses of the contractile segment (CS) were computed by Janz's method. RESULTS: The total ejection fraction (EF) increased (p < 0.01) in the LVA group, whereas it did not change in the CABG group at 8 months after surgery. Both the end-diastolic and end-systolic volume indices of CS decreased (p < 0.01 and p < 0.01, respectively) in the LVA group, whereas both remained unchanged in the CABG group. The mean velocity of circumferential fiber shortening (mean Vcf) of CS increased substantially (p < 0.01) in the LVA group and, less significantly (p < 0.05), in the CABG group. Regional ESS and EDS decreased (p < 0.01 and p < 0.05, respectively) in the LVA group, whereas both remained unchanged in the CABG group. The increase in mean Vcf correlated strongly with the magnitude of decrease in ESS (r = -0.63, p < 0.01) in the LVA group but not in the CABG group. CONCLUSIONS: LVA can reduce regional afterload and improve ejection performance of the noninfarcted myocardium in many patients with a large anterior LV aneurysm and, moreover, may favorably affect the LV remodeling process after MI.

Cardiac Catheterization↗

Activation of lymphocytes by HHV-6 antigen in normal children and adults.

We investigated the immune reaction of lymphocytes in response to human herpes virus-6 (HHV-6) in normal children and adults. Cell proliferation was assayed by measurement of the incorporation of 5-bromo-2'-deoxyuridine (BrdU) by enzyme-linked immunosorbent assay (ELISA), and changes in expression of interleukin-2 receptors (IL-2Rs) (alpha-, beta3-, and gamma-chain) were assayed by flow cytometry. Incorporation of BrdU and expression of IL-2Rs (alpha-, beta-, and gamma-chain) in CD4+, CD8+, and CD45RO+ lymphocytes were increased when peripheral blood mononuclear cells (PBMC) from HHV-6 seropositive children aged 3 to 12 years and adults were cultured with HHV-6 antigen compared with control antigen. In contrast, cord blood mononuclear cells (CBMC) and PBMC from seronegative children did not show cell proliferation and changes in expression of IL-2Rs. In seropositive children less than 2 years of age, the magnitude of cell proliferation was low and IL-2Rs (alpha-, beta-, and gamma-chain) in CD8+ cells and IL-2Rs (alpha-chain) in CD45RO+ cells were increased. These data suggest that children below the age of 2 had immature lymphocytic response to HHV-6 antigen. Deletion of monocytes from PBMC and the addition of a mixture of anti-IL-2Rs (alpha-, beta-, and gamma-chain) antibodies reduced cell proliferation in response to HHV-6, suggesting the requirement of the presence of monocytes and expression of IL-2Rs.

Adult↗

Inductions of 3-L-nitrotyrosine in motor neurons after transient spinal cord ischemia in rabbits.

The induction and distribution of 3-L-nitrotyrosine (NO2-Tyr) were examined with HPLC and immunohistochemistry in rabbit spinal cords after 15 minutes of transient ischemia until 7 days of the reperfusion. After the 15-minute ischemia, there was a significant decrease of neurologic scores in the ischemic group compared with the sham-operated control group at 7 days of reperfusion (P = 0.0017), and the majority of motor neurons was selectively lost at 7 days of reperfusion (P = 0.0039). NO2-Tyr was transiently induced at 8 hours of reperfusion in the ventral part of the spinal cord (0.47%+/-0.86%, NO2-Tyr/total tyrosine; P = 0.0021), but was not induced at any time point of reperfusion in the dorsal part of the spinal cord. Strong immunoreactivity for NO2-Tyr was selectively induced in large pyramidal motor neurons at 8 hours of reperfusion and was still weakly present until 7 days of reperfusion. (There may be a difference in sensitivity between the two techniques.) These results suggested that protein tyrosine nitration by nitric oxide plays a role in the selective motor neuron cell damage after transient spinal cord ischemia.

Animals↗

The ecdysteroid UDP-glucosyltransferase gene of Autographa californica nucleopolyhedrovirus alters the moulting and metamorphosis of a non-target insect, the silkworm, Bombyx mori (Lepidoptera, Bombycidae).

The Autographa californica nucleopolyhedrovirus (AcMNPV) does not infect the silkworm and molecular studies on silkworm insusceptibility have not been performed. In cultured cells of the silkworm, the expression of viral genes has been reported. The expression of AcMNPV genes and their effect in vivo and in vitro was studied. In this study, the early gene, the ecdysteroid UDP-glucosyltransferase (egt) gene of AcMNPV, which inactivates the insect moulting hormone by sugar conjugation, was examined to determine whether it would alter the growth of the silkworm. Using wild-type (wt) AcMNPV, the egt gene deletion virus (vEGTDEL), and the virus carrying the egt promoter-lacZ cassette in vEGTDEL (vEGTZ), the egt promoter-driven expression in cultured cells and in nonproductive infection of the silkworm was characterized. Infection of cultured cells with vEGTZ at three different doses occurred in a single cell manner. When budded wt AcMNPV was injected into the fourth and fifth instar larvae, an increase in the amount of virus occurred and caused abnormal larval growth, which resulted in the prolongation or skipping of the larval instar, premature pupation, or death during the pupal stage. For infection of the fourth instar larvae, precocious metamorphosis was observed. When the same amount of vEGTDEL was injected, the alteration of growth did not occur. These results suggest that the egt gene was expressed in the primary infected cells of the silkworm, and that the EGT was secreted into the haemocoel, which significantly altered larval growth.

Animals↗

Suppressive effect of the angiogenesis inhibitor TNP-470 on the development of carcinogen-induced hepatic nodules in rats.

Tumor metastasis can be prevented by inhibiting angiogenesis. In the present study, we have demonstrated that the angiogenesis inhibitor TNP-470 also suppresses the development of primary hepatic nodules. Hepatocarcinogenesis was performed by the feeding of 2-acetylaminofluorene to hepatectomized rats during 8-14 weeks of age. Predominantly arterial-to-portal circulation and sinusoidal capillarization were determined by the staining of nodules with arterially infused ink and immunostaining for factor VIII-related antigen, respectively. Intraperitoneal administration of 30 mg/kg b.w. of TNP-470 twice a week significantly reduced the number of hepatic nodules. Among the nodules, hyperplastic nodules stained with ink, atypical hyperplastic nodules and hepatocellular carcinoma, all of which possess structurally altered sinusoidal endothelial cells or capillary-type endothelial cells, were dramatically decreased in number. Suppression was observed equally in nodules of all sizes. TNP-470 was more effective when administered during 8-20 weeks than during 14-26 weeks. In contrast, ink-non-stained hyperplastic nodules, which have normal sinusoidal endothelial cells, were not affected at all. The present results indicate that TNP-470 suppresses the development of primary hepatic nodules whose microvessels are capillaries or transitional forms from sinusoids to capillaries.

2-Acetylaminofluorene↗

Molecular analysis of HLA class I (HLA-A and -B) and HLA class II (HLA-DRB1) genes in Japanese patients with multiple sclerosis (Western type and Asian type).

The types of HLA-A, -B and -DRB1 genes were studied in 146 Japanese patients with multiple sclerosis (MS) using polymerase chain reaction-sequence-specific oligonucleotide probe analysis. Fifty-seven patients who displayed selective clinical involvement of the optic nerve and spinal cord were classified as having Asian type MS. The other 89 patients had disseminated central nervous system involvement and were classified as having Western type MS. The frequency of HLA-B*5101 was increased in both types of MS patients compared with controls. The frequency of HLA-DRB1*1501 was increased in Western type MS and the frequency of HLA-DRB1*0802 was increased in Asian type MS compared to controls. After correction of P values, the association of Western type MS patients with HLA-DRB1*1501 was statistically significant (Pc=0.0003) whereas other HLA alleles showed no significant association. These results suggest that HLA class I (HLA-A and -B) alleles may not contribute to a strong susceptibility to MS in Japanese compared to HLA class II (HLA-DRB1) alleles.

Alleles↗

Hyperplastic foci in chronic liver disease: their proliferative activity assessed by nucleolar organizing region.

In the cirrhotic and precirrhotic liver, there may be small foci with increased cellularity and amphophilic cytoplasm. These are microscopic lesions that do not form macroscopically detectable nodules, which differ from the macroscopically apparent nodules of dysplastic nodules. In the present study, we assessed the proliferating activity of 12 hyperplastic foci in 11 patients with cirrhosis or chronic hepatitis, by staining for agyrophilic nucleolar organizing regions (AgNOR). The mean AgNOR count per nucleus in the hyperplastic foci ranged from 0.96 to 1.36 (mean, 1.13; SD 0.12), and from 0.81 to 1.06 (mean, 0.94; SD 0.08) in the controls. The AgNOR count in the hyperplastic foci was significantly higher than that in the controls (P < 0.01). Small hyperplastic foci show increased proliferative activity. Further study on these foci is required to clarify their relation to hepatocarcinogenesis.

Adult↗