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Biomedical subjects

Y Suehiro

Publications and source records attributed to Y Suehiro.

At least 19 recordsLinked to original sources

Sequence and expression analyses of mu and delta transcripts in patients with Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia (WM) is a malignant lymphoplasmo-proliferative disorder with monoclonal pentameric immunoglobulin (Ig)M production. The most consistent feature of clonal B cells in the bone marrow (BM) and/or lymph nodes of patients with WM is the presence of pleomorphic B-lineage cells at different stages of maturation, such as small lymphocytes, lymphoplasmacytoid cells, and plasma cells. Monoclonal lymphocytes express mu chains with or without delta chains. A recent DNA analysis of WM tumor clones showed WM to be derived from B cells that have been selected by antigen at a relatively late stage of differentiation. To further clarify the origin of WM tumor cells, we analyzed the variable (V) domain sequences of tumor derived mu and delta transcripts. The expression of delta transcripts was also examined in peripheral blood (PB) and BM using the reverse transcriptase polymerase chain reaction (RT-PCR) combined with a single-strand conformation polymorphism (SSCP) analysis. The sequences were identical among the mu and delta transcripts in each patient and the level of somatic mutation in the VH regions expressed by tumor cells was in the same range as that of IgM-only B cells and IgM(+)IgD(+) memory B cells. In our previous RT-PCR-SSCP analysis, a single dominant band of the mu isotype was observed in BM and PB in all patients. However, common dominant bands in BM and PB were detected in only one patient in a delta transcript analysis. In the rest of the patients, monoclonal delta transcripts were only detected in BM. Our results suggest that a normal counterpart of WM cells is somatically mutated IgM(+)IgD(+) and/or IgM-only B cells and the expression patterns of monoclonal mu and delta transcripts differ between BM and PB in some cases of WM.

Blood Cells↗

A case of 46,X,der(X)(pter-->q21::p21-->pter) with gonadal dysgenesis, tall stature, and endometriosis.

OBJECTIVE: To report a case of 46,X,der(X)(pter-->q21::p21-->pter) with gonadal dysgenesis, tall stature, and endometriosis. DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A 20-year-old primary amenorrheal woman receiving estrogen-progestogen substitution. INTERVENTION(S): G-banding, comparative genomic hybridization, fluorescence in situ hybridization (FISH), and laparoscopy. MAIN OUTCOME MEASURE(S): A recombinant X chromosome, 46,X,der(X)(pter-->q21::p21-->pter), and pelvic endometriosis. RESULT(S): The patient's chromosomal abnormality was misjudged by the use of G-banding as a distal part deletion of the long arm in one X chromosome. Comparative genomic hybridization and fluorescence in situ hybridization analyses with locus-specific probes revealed 46,X,der(X)(pter-->q21::p21-->pter). The laparoscopic examination showed bilateral streak gonads and blue berry spots at the pelvic peritoneum, which were confirmed by evaluation of biopsy specimens. CONCLUSION(S): Recent advances of genetic strategies make it easy to determine karyotype and phenotype abnormalities. We have to keep our mind on the potential of endometriosis with patients who are receiving estrogen-progestogen substitution.

Adult↗

Combined examination of p27(Kip1), p21(Waf1/Cip1) and p53 expression allows precise estimation of prognosis in patients with gastric carcinoma.

AIMS: In order to estimate the prognostic values of p27(Kip1), p21(Waf1/Cip1), and p53, alone and in combination, we investigated immunohistochemically the expression of p27(Kip1), p21(Waf1/Cip1), and p53 proteins in gastric carcinomas. METHODS AND RESULTS: The expression of p27(Kip1), p21(Waf1/Cip1), and p53 was immunohistochemically examined in 140 gastric carcinomas. Positive expression of p27(Kip1) and p21(Waf1/Cip1) correlated significantly with a favourable prognosis (P < 0.05), whereas, positive expression of p53 tended to correlate with poor prognosis. Multivariate survival analysis revealed that TNM stage of tumour (P < 0.001), lymph node state (P=0.005), and p27(Kip1) expression (P=0.006) were independent prognostic factors. A striking stratification of mortality rate was found when patients were divided into four groups according to the expression of p21(Waf1/Cip1) and p27(Kip1). The mortality rate was higher in patients with both p21(Waf1/Cip1)- and p27(Kip1)-negative gastric carcinoma than in patients with one or both positive carcinomas (P < 0.01). In addition, if the four p21(Waf1/Cip1)/p27(Kip1) groups were compared based on p53 status, p53+ cases tended to have a higher mortality rate than p53- cases. CONCLUSION: Our results suggest that low expression of both p27(Kip1) and p21(Waf1/Cip1), could be useful as markers of poorer prognosis, and the combined examination of p27(Kip1), p21(Waf1/Cip1) and p53 expression allows reliable estimation of prognosis for patients with gastric carcinoma.

Adult↗

Aberrant BCR-ABL transcript with intronic insertion in a patient with philadelphia chromosome-positive chronic myeloid leukemia: implications for disease progression.

The BCR-ABL fusion gene is important for the leukemogenesis of chronic myeloid leukemia (CML). A relationship between types of BCR-ABL transcripts in CML and clinical features has been proposed. We present here a patient with CML who carried an aberrant BCR-ABL transcript with an intronic sequence insert. A 26-year-old woman was diagnosed as having Philadelphia chromosome (Ph) positive CML. Reverse transcription polymerase chain reaction detected an atypically large BCR-ABL mRNA transcript. Sequencing revealed a 589bp insertion consisting of a 5' portion of BCR intron b2 and a 3' portion of ABL intron 1b between BCR exon b2 and ABL exon a2. Although the typical b2a2 transcript was undetectable initially, it appeared after intensive chemotherapy. The aberrant transcript presumably arose as a result of a lack of splicing, and chemotherapy might modify the disease course by selecting the subpopulation of the CML clone expressing typical BCR-ABL mRNA dominantly.

Adult↗

New molecular tumor markers for endometrial cancer.

Although the International Federation of Gynecology and Obstetrics officially changed the classification system of endometrial cancer from a clinically staged to a surgically staged disease in 1988, optimal management of patients with endometrial cancer is still controversial. Gynecologists happen to experience that patients with tumors that are identical in grade and stage often have significantly different clinical outcomes or responses to therapy. In order to identify an objective biological factor correlating with tumor aggressiveness, many tumor markers have been investigated. So far, CA125 is one of the most reliable tumor marker for adenocarcinoma of the uterus and frequently used in a clinical setting. Recently, with the advent of molecular biological techniques, many genes and regions of the genome related to endometrial cancer have been identified. We undertook a genome-wide screening to detect genetic changes by comparative genomic hybridization (CGH) in primary endometrioid cancers, since CGH analysis provides comprehensive information concerning relative chromosomal losses and gains in tumors by a single hybridization. In this paper, the usefulness of serum tumor markers and the new promising molecular tumor markers for endometrial cancer are discussed.

Biomarkers, Tumor↗

Genetic aberrations detected by comparative genomic hybridization predict outcome in patients with endometrioid carcinoma.

Endometrial cancer progression is determined by a complex pattern of multiple genetic aberrations, but how these aberrations affect prognosis is unknown. In this study, we undertook a genome-wide screening to detect genetic changes by comparative genomic hybridization (CGH) in 51 tumors from patients with primary endometrioid carcinoma of the uterine corpus. The observed genetic changes were subsequently correlated with the progression of the disease and the clinical outcome in each case. The average number of genetic aberrations (copy number gains and losses) was significantly greater in non-surviving patients than in disease-free patients (12. 6 vs. 2.7, P < 0.0001). According to multivariate analysis, lymph node metastasis (P = 0.015), cervical involvement (P = 0.007) and one or more copy number losses at 9q32-q34, 11q23, or Xq12-q24 (P = 0.023) were significantly predictive of death from the disease. Interestingly, lymph node metastasis was significantly associated with copy number gains at 8q22-q23 and 8q24-qter (P = 0.003 and P = 0.025, respectively). Moreover, cervical involvement was also correlated significantly not only with gains of 8q22-q23 and 8q24-qter but also with loss of 11q23 (P = 0.04, 0.0003, and P = 0. 009, respectively). These results suggest that analysis of genetic changes may help predict clinical outcome and the presence of metastatic disease as well as assist in therapeutic decision making for patients with endometrioid carcinoma.

Adult↗

Electrophysiological studies of a child with presumed botulism.

Electrophysiological studies of a child with presumed botulism showed that the amplitude of the serially and electrically elicited blink reflexes Rl, R2 and R2' was reduced during recovery. These findings suggest a conduction block of the facial nerves. Other nerve conduction studies and an incremental response to repetitive stimulation demonstrated a block of the presynaptic neuromuscular transmission. Results of the biological tests were negative, but those of electrodiagnosis and clinical examination favored a diagnosis of botulism. A combination of electrically elicited blink reflexes and rapid repetitive stimulation of the peripheral nerves was found to be a sensitive method of assessing the integrity of neuromuscular junctions and the subclinical impairment of muscle nerves.

Blinking↗

Genetic aberrations detected by comparative genomic hybridization in ovarian clear cell adenocarcinomas.

Genetic abnormalities were detected by comparative genomic hybridization (CGH) in 12 ovarian clear cell adenocarcinomas. DNA sequence copy number abnormalities (CNAs) occurring in more than 20% of the cancers included increased copy numbers of 8q11-q13, 8q21-q22, 8q23, 8q24-qter, 17q25-qter, 20q13-qter and 21q22-qter and reduced copy numbers of 19p. Increases in copy numbers of 8q11-q13, 8q21-q22, 8q23 and 8q24-qter occurred more frequently in disease-free patients than in recurrent/non-surviving patients (p < 0.05). However, increases in copy numbers of 17q25-qter and 20q13-qter occurred more frequently in recurrent/non-surviving patients than in disease-free patients (p < 0.05). Furthermore, increases in copy numbers of 17q25-qter and 20q13-qter occurred together (p < 0.05). Additionally, there were negative correlations between increases in copy numbers of 8q21-q22 and 17q25-qter, and between 8q21-q22 and 20q13-qter (p < 0.05). It appears that ovarian clear cell adenocarcinomas can be classified into two subtypes, one being cancer with an increase in copy numbers of 8q and the other being cancer with increases in copy numbers of 17q25-qter and 20q13-qter.

Adenocarcinoma, Clear Cell↗

Macrophage inflammatory protein 1alpha enhances in a different manner adhesion of hematopoietic progenitor cells from bone marrow, cord blood, and mobilized peripheral blood.

Regulatory mechanisms governing adhesion of hematopoietic progenitor cells to the stromal nische are poorly understood. Growth factors such as stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor, and thrombopoietin were reported to upregulate the adhesion of hematopoietic progenitors to immobilized fibronectin through activation of integrin alpha4beta1 and alpha5beta1. Macrophage inflammatory protein (MIP)-1alpha is a C-C chemokine that suppresses colony formation by stem/progenitor cells in vitro. We asked if MIP-1alpha would modulate the adhesive phenotype of colony-forming cells (CFCs) obtained from healthy donor bone marrow (BM), cord blood (CB), and mobilized peripheral blood (mPB) CD34+ cells, in comparison with SCF, using immobilized fibronectin. SCF significantly increased the level of adhesion of CFCs from BM, CB, and mPB. On the other hand, MIP-1alpha significantly increased the level of adhesion of CFCs from BM and CB, but less so from mPB. The effects of MIP-1alpha were inhibited by blocking antibodies to integrin alpha4, alpha5, or beta1, and polymerization plus rearrangement of F-actin were observed in affected cells by labeling with rhodamine-conjugated phalloidine. These data indicate that the effect of MIP-1alpha on the adhesive phenotype of CFCs is mediated by modulation of the organization of integrin. The amount of MIP-1alpha receptor on mPB was less than for BM or CB, which may explain the distinct characteristics in the adhesive response induced by MIP-1alpha. We suggest that hematopoietic progenitor cells from different sources may be heterogeneous with respect to maturation, integrin affinity, MIP-1alpha receptor expression, and regulation of MIP-1alpha signaling. Our data indicate that MIP-1alpha may affect migration, homing, and mobilization of hematopoietic progenitors by modulating the adhesive phenotype of these cells.

Actins↗

[Donor leukocyte transfusion in a patient with relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation: analysis of natural killer cell activity and T-cell receptor repertoire in bone marrow T cells that exhibited graft-versus-leukemia activity].

Hematologic relapse of chronic myeloid leukemia developed in 37-year-old man 255 days after allogeneic bone marrow transplantation. The patient received a donor lymphocyte transfusion (DLT) twice at a dose of 5 x 10(6)/kg T cells. He achieved complete cytogenetic response (CCR) 14 weeks after DLT, and has remained in a CCR state for 17 months. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. Natural killer (NK) cell activity was elevated. Also, analysis of the T cell receptor (TCR) repertoire disclosed oligoclonal expansion of T cells of the TCR V beta and J beta subfamilies. These observations provide evidence for the clonal expansion of allogeneic T cells that are capable of mediating antileukemic activity without causing GVHD.

Adult↗

Anti-emetic effects of a novel NK-1 receptor antagonist HSP-117 in ferrets.

We have developed a non-peptide compound, HSP-117, antagonist of the tachykinin NK-1 receptor. Binding of 3H-substance P (SP) to the membranes of IM-9 cells was inhibited by the antagonists HSP-117 and CP-99,994, the inhibitory activity of HSP-117 being about 50-fold that of CP-99,994. The SP-induced firing responses of single neuron activity in slices of the nucleus tractus solitarius of ferrets were inhibited by 10 microM HSP-117. Intracerebroventricular injection of HSP-117 significantly inhibited retching and vomiting induced by copper sulphate and morphine and the inhibitory effect of HSP-117 on emesis was greater than that of CP-99,994. These results indicate that (1) HSP-117 is a potent anti-emetic agent, blocking NK-1 receptors in the nucleus tractus solitarius and (2) NK-1 receptors in the nucleus tractus solitarius play an important role in emesis induced by broad-spectrum emetic stimuli.

Animals↗

Successful treatment of a patient with cardiac lymphoma who presented with a complete atrioventricular block.

A patient with primary cardiac lymphoma, which is very rare, generally is regarded to have a poor prognosis. We herein report a patient with cardiac lymphoma who was treated successfully by systemic chemotherapy and radiotherapy using a pacemaker to control the complete atrioventricular (A-V) block. A 70-year-old man had a syncope caused by a complete A-V block. An echocardiogram, a computed tomographic scan, and magnetic resonance imaging of his chest showed a cardiac tumor. At this time, a biopsy of the cardiac tumor disclosed malignant lymphoma (diffuse large cell type, B cell type). The patient was thus treated with systemic chemotherapy and radiotherapy and, as a result, achieved a complete remission with a disappearance of the A-V block. Recently, several successful outcomes involving primary cardiac lymphoma have been reported because of the progress in diagnostic techniques including echocardiography, computed tomographic scanning, and magnetic resonance imaging, as well as improvement in the therapy of malignant lymphoma. Our clinical experience indicated that an early and accurate diagnosis combined with the appropriate therapy can thus help in obtaining a long survival in patients with primary cardiac lymphoma.

Aged↗

[Chlamydia pneumoniae infection in children with asthma exacerbation].

Little is known about the significance of C. pneumoniae in wheezing state in children. In this study, a total of 33 children with exacerbation of bronchial asthma were serologically and bacteriologically analyzed to investigate whether C. pneumoniae infection is associated with wheezing in children with bronchial asthma. 1) Of the 33 patients 12 (39%) had an acute antibody rise against C. pneumoniae. C. pneumoniae was isolated from 8 patients (24%) by culture. Based on these findings, 15 cases (45%) were diagnosed as C. pneumoniae infection. 2) There were no significant difference in clinical signs, symptoms and laboratory studies between with and without C. pneumoniae infection. The high incidence of C. pneumoniae infection in children with exacerbation of bronchial asthma suggests its significance as a cause of wheezing. Although there was no specific symptom in C. pneumoniae infection, this infection should be suspected in wheezing children for diagnosis and proper treatment.

Adolescent↗

[Cancer-associated gene abnormalities and chemosensitivity].

One of the most important clinical issues in cancer chemotherapy is the presence of intrinsic resistance or the appearance of acquired resistance against chemotherapy. As for intrinsic resistance, we had to perform direct chemo-sensitivity testing, or had to rely on the knowledge empirically acquired from randomized clinical trials. However, molecular or genetic markers associated with chemo-sensitivity have been reported recently. For example, inactivation of p53 or GML gene has been reported to be associated with chemo-resistance. Overexpression of topo-isomerase I has been reported to be associated with chemo-sensitivity to Topo I inhibitor. Overexpression of Thymidine Phosphorylase has been found to be associated with chemo-sensitivity to prodrug of 5-FU. By checking the status of such chemo-sensitivity markers prior to chemotherapy, it would be possible to predict the chemotherapeutic effect and even the necessity of the chemotherapy in the near future. In this article, we review the chemo-sensitivity markers reported so far, and methodology contributing to the discovery of new chemo-sensitivity markers. As a clinical study, 11 cases of ovarian cancer with high sensitivity to cisplatin-based chemotherapy and 29 cases of ovarian cancer with chemoresistance were analyzed by Comparative Genomic Hybridization (CGH). Copy number decrease in Xp, and copy number increase in 19q were observed in 13, 12 out of 29 resistant cases (45, 41%) and zero, 1 out of 11 sensitive cases (0, 9%), suggesting that -Xp and +19q were likely to be a genetic event associated with intrinsic drug-resistance (p = 0.006, 0.05, respectively). This effort should contribute to the discovery of new chemo-sensitivity and resistance markers.

Antineoplastic Agents↗

High occurrence of primary malignant neoplasms in patients with adult T-cell leukemia/lymphoma, their siblings, and their mothers.

BACKGROUND: Attempts were made to clarify the correlation between human T-cell leukemia/lymphoma virus (HTLV)-1 infection and malignant oncogenicity other than adult T-cell leukemia/lymphoma (ATL) in a case-control study. METHODS: The occurrence of primary malignant neoplasms (MN) in 110 ATL patients, their parents, and 430 siblings was compared with HTLV-1 seronegative non-Hodgkin's lymphoma (NHL) patients, their parents and 867 siblings. The chi-square test, odds ratio (OR), and 95% confidence intervals (CI) were used to determine the statistical significance of differences in the occurrence of the primary MN among ATL patients, HTLV-1 seronegative NHL patients, their siblings, and their parents. RESULTS: The occurrence of primary MN in the ATL patients was higher than the occurrence in HTLV-1 seronegative NHL patients (P = 0.0036; OR = 2.91; 95% CI: 1.42, 6.02). In siblings of the ATL patients, there was a higher occurrence of primary MN than in siblings of the HTLV-1 seronegative NHL patients (P < 0.0001; OR = 3.35; 95% CI: 2.01, 5.58). In mothers of the ATL patients, there was a higher occurrence of primary MN than in mothers of the HTLV-1 seronegative NHL patients (P = 0.0063; OR = 2.55; 95% CI: 1.30, 5.00), but not in fathers (P = 0.1602; OR = 1.68; 95% CI: 0.81, 3.47). CONCLUSIONS: There is an increased risk of primary MN in ATL patients, their siblings, and their mothers.

Aged↗

[Photodynamic therapy (PDT) for early cervical cancer].

The incidence of carcinoma in situ (CIS) and dysplasia of the uterine cervix has been increasing among young women in recent years. Most of these patients want to preserve their fertility. Also, to accommodate high-risk patients with complications, elderly patients, and those who refuse surgery, we perform PDT as a method to preserve fertility. The technique required for PDT is relatively simple, and can be performed without anesthesia, since it causes no pain or bleeding. PDT, with the use of Excimer Dye Laser (EDL), a type of low pulse laser, has a considerably higher degree of tissue penetration, even compared to PDT using Argon Dye Laser (ADL). Also, PDT using EDL can manage glandular involvement of CIN, and its special feature of selective destruction of malignant cells with almost no effect on normal tissues is noteworthy. Beginning in 1995, PDT using YAG-OPO Laser with a variable laser wavelength has been performed. PDT is performed 48 hours after intravenous injection of 1.5 mg/kg to 2 mg/kg photosensitizer Porfimer sodium (PHE) when the difference in density of PHE becomes greatest between malignant cells and normal tissue. The most advanced features of our method compared to conventional radiation which uses cut fiber are: First, by using colposcope with an optical path for the laser, it is possible to show a 10 mm circular spot at the focus of observation. With this method, cervical lesions can be observed and checked while receiving stable and precise photoradiation by using colposcope through direct observation. Second, for cervical canal treatment, by using a cervical probe to administer photoradiation in the forward direction in the cervical canal and to the side walls, 70% of the laser light is scattered to the side walls, so that all of the cervical canal can be radiated. Also, the cervical canal probe used to administer photoradiation, by inserting 2 cm to 3 cm depending on the conditions of the cervical canal and withdrawing the probe 1 mm, can be performed precisely and promptly by using the cervical probe manipulator feature of the colposcope. At the present time, studies using the PDT method have been conducted on 56 patients (39 CIS and 17 dysplasia patients). Out of these 56 patients, there were 54 CR (96.4%), only one NC, and one PR with very limited remnants but most of the lesions had disappeared. The NC was highly suspected to be invasive carcinoma and the PR was CIS. In the CIS case, some remnant was evident at the end of the cervical canal, and PDT was administered again. After this treatment, it became CR. This was 10 months ago, and no abnormal condition has been reported since. The first CR case was reported 6 years ago among the 56 cases studied, and no recurrence has been observed to date. Five patients became pregnant after the treatment. Four had normal deliveries and one had a cesarean section. PDT's side effect is similar to symptoms of sunburn such as minor skin irritation due to sensitive reaction to sunlight. Normally, it can be relieved by applying carmine lotion, and even cases that required treatment were cured completely within a few days after applying steroid ointment. Before hospitalization, if the patient gets a sunburn from being outside, the sensitive reaction to laser light is almost nonexistent. Thus, we advise patients to get some exposure to the sun before being hospitalized. Also, in cases where strict shading time is observed, side effects are not apparent at all, and no abnormal findings are recognized in the blood and urine due to using PHE. With almost no side effects, bleeding or pain, and with certain improvements in administration methods, a better choice of photosensitizer which would shorten the shading time, PDT is considered to be the best therapy for treating CIS and dysplasia while preserving fertility.

Adult↗