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Biomedical subjects

S Miyake

Publications and source records attributed to S Miyake.

At least 181 records · Page 10Linked to original sources

[Metastasis of an adenocarcinoma of unknown origin to mediastinal lymph nodes, and transient regression].

A 67-year-old woman was admitted to our hospital because of fever. Chest roentgenogram showed an enlargement of mediastinal lymph nodes. Despite thorough examination, no definite diagnosis could be made. The mediastinal lymph nodes got smaller over the next 3 weeks and a chest roentgenogram taken 4 months later showed no mediastinal lymphadenopathy. The mediastinal lymphadenopathy and fever recurred 5 months later. She underwent thoracotomy and the mediastinal lymph nodes were excised. Microscopic examination of pretracheal lymph node specimens showed invasion of poorly differentiated adenocarcinoma associated with abundant tumor-infiltrating lymphocytes. The other lymph nodes showed sarcoid reaction. Although she has been followed for one year and 11 months, no primary site of the cancer has been found. Metastasis of cancer of unknown origin to mediastinal lymph nodes is extremely rare. It is also interesting that the lymph node swelling diminished spontaneously. The tumor-infiltrating lymphocytes and sarcoid reactions may have been immunological responses to the cancer and may have caused the transient regression.

Adenocarcinoma↗

Increase in adhesion molecules on CD4+ cells and CD4+ cell subsets in synovial fluid from patients with rheumatoid arthritis.

OBJECTIVE: To elucidate the role of adhesion molecules in the pathogenesis of rheumatoid arthritis (RA). METHODS: We evaluated their expression and that of an activation marker on CD4+ cell populations and CD4+ cell subsets in specimens of peripheral blood (PB) and synovial fluid (SF) obtained from 10 patients with RA and 7 with osteoarthritis (OA). A 2 or 3-color immunofluorescent method was used for analysis. RESULTS: The SF from both groups of patients showed a greater density of adhesion molecules including LFA-1 alpha, LFA-1 beta, CD2, VLA-4 alpha and VLA-5 alpha on CD4+ cells, and a higher percentage of CD4+HLA-DR+ cells compared with their PB. IN PB-CD4+ cell subsets from the arthritic and healthy subjects, the CD4+CD45RO+ cell population showed an increased expression of adhesion molecules compared with CD4+CD45RA+ cell population. The expression of adhesion molecules on circulating CD4+ cell population and CD4+ cell subsets from the patients with RA and OA was comparable to that from healthy subjects. SF from both groups of patients showed a higher percentage of CD4+CD45RO+ cells and a lower percentage of CD4+CD45RA+ cells. In SF-CD4+ cell subsets from patients with RA, the CD4+CD45RO+ cell population had an increased expression of VLA-4 alpha compared to the CD4+CD45RA+ cell population; however, there was no significant difference in other adhesion molecule expression and the percentage of HLA-DR+ cells between the 2 cell subsets. Furthermore, the expression of VLA-4 alpha on the CD4+CD45RO+ cell population in SF from patients with RA was significantly higher than that in matched PB. In CD4+CD45RA+ cell population from both groups of patients, SF showed an enhanced expression of adhesion molecules and an increased percentage of HLA-DR+ cells compared with matched PB. CONCLUSION: Our results suggest that increased expression of adhesion molecules and increased percentage of HLA-DR+ cells on CD4+ cells in SF may be responsible for cellular interactions between these cells and synovial cells or extracellular matrix.

Adult↗

Combined therapy with arbekacin and fosfomycin for methicillin-resistant Staphylococcus aureus infections.

We examined the clinical efficacy of a combination of arbekacin and fosfomycin in the treatment of various methicillin-resistant Staphylococcus aureus (MRSA) infections. The combination of arbekacin plus fosfomycin displayed 65.4% (17/26) clinical efficacy and 65.4% (17/26) bacteriological efficacy. This combination thus appeared to be an effective regimen for the treatment of MRSA infections. However, its bacteriological efficacy against concomitant Pseudomonas aeruginosa strains was only 16.7% (1/6). In addition, in 4 episodes of superinfection involving P. aeruginosa strains developed during the combination therapy.

Aminoglycosides↗

DNA alterations in cells from hereditary non-polyposis colorectal cancer patients.

To determine if the MCC, DCC or p53 gene is associated with susceptibility to hereditary non-polyposis colorectal cancer (HNPCC), these genes in normal cells from 12 HNPCC patients were analysed by polymerase chain reaction-single strand conformation polymorphism analysis. No changes which may alter the amino acid sequences of these genes were detected, suggesting that these genes are not associated with the susceptibility to HNPCC. Only one of nine HNPCC cancers showed mutations in the MCC and p53 genes on the same analysis. Loss of heterozygosity in chromosomes 5q, 17p, 18q and 22 was detected in four of the nine cancers, all of them being positive as to metastasis to lymph nodes. Abnormalities of the (CA)n repeat were found in six cancers, including all four without metastasis. These data indicate that tumor suppressor genes in chromosomes 5q, 17p, 18q and 22 are associated with the late stage of colorectal tumorigenesis in HNPCC, whereas the (CA)n repeat abnormalities are an early event of tumorigenesis and more essential to HNPCC.

Adult↗

[A case of crescentic glomerulonephritis associated with anti-myeloperoxidase antibody presenting as alveolar hemorrhage].

A 77-year-old man was admitted because of hemoptysis. Chest roentgenograms initially showed progressive infiltrative shadows, which improved spontaneously in 3 months. Transbronchial lung biopsy specimens obtained during the first admission revealed alveolar hemorrhage with neither granuloma nor vasculitis. Alveolar hemorrhage associated with renal dysfunction recurred 9 months later. Serum creatinine level was elevated to 3.5 mg/dl. No other organ than lungs or kidneys was involved. Renal biopsy was performed to confirm the pathological diagnosis of crescentic glomerulonephritis. Anti-basement-membrane antibody was negative, whereas anti-neutrophil-cytoplasmic antibody was positive for perinuclear pattern (P-ANCA) by indirect immunofluorescent (IF) method. He was diagnosed as having idiopathic crescentic glomerulonephritis complicated with alveolar hemorrhage, and the presence of anti-myeloperoxidase (MPO) antibody in serum was anticipated. Anti-MPO antibody level in his serum evaluated by ELISA was markedly elevated. Although myeloperoxidase has been considered as a common antigen to P-ANCA and anti-MPO antibody, the determination of P-ANCA has been clinically unreliable because of equivocal results. In contrast, the presence of anti-MPO antibody is highly specific for idiopathic crescentic glomerulonephritis complicated with alveolar hemorrhage or its incomplete variant case. Also, it is a better index of disease activity. Therefore, there is a possibility that those patients diagnosed as having idiopathic pulmonary hemosiderosis or pulmonary-renal syndrome may be categorized into the one disease, anti-MPO antibody-associated disease, and the measurement of anti-MPO antibody may lead to prompt treatment prior to the histological diagnosis.

Aged↗

Optimization of nonradioisotopic single strand conformation polymorphism analysis with a conventional minislab gel electrophoresis apparatus.

We have developed a means of nonradioisotopic single strand conformation polymorphism (nonRI-SSCP) analysis and applied it to the detection of a point mutation in the human tumor suppressor gene, p53. The method does not require any particular facilities or apparatus, such as a laboratory for radioactive materials, a large gel unit for sequencing, or a semiautomated electrophoresis system. This technique comprises amplification of DNA fragments by the PCR technique with specific oligonucleotide primers, denaturation, and electrophoresis on neutral polyacrylamide gels in a conventional minislab apparatus. The SSCP patterns on electrophoresis were detected with a commercially available silver stain method. We also evaluated various electrophoretic conditions for nonRI-SSCP analysis, such as the gel concentration and buffer components. A tris/glycine buffer system gave better resolution of SSCP bands. The SSCP patterns of different sized DNAs could be analyzed in a gradient polyacrylamide gel. Thus, nonRI-SSCP analysis with a conventional minislab gel electrophoresis apparatus can be satisfactorily substituted for a commonly used RI-SSCP technique.

Base Sequence↗

Beta 1 integrin-mediated interaction with extracellular matrix proteins regulates cytokine gene expression in synovial fluid cells of rheumatoid arthritis patients.

Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis (RA), whereas the mechanisms for constitutive production of inflammatory cytokines in affected joints are largely unknown. Recently, integrin-mediated interaction with extracellular matrix (ECM) proteins has been demonstrated to play a role in regulating cytokine production in T cells and monocytes. In this study, we investigated the contribution of the beta 1 integrin-mediated interaction with ECM proteins to the persistent cytokine gene expression in RA synovial fluid mononuclear cells (SFMNC). We examined mRNA expression of 14 cytokines in the SFMNC of three RA patients, which were either fresh or cultured overnight in serum-free medium on ECM-coated plates, by polymerase chain reaction with a panel of oligonucleotide primers specific for each cytokine. The persistent expression of various cytokine mRNA found in fresh SFMNC was maintained after overnight culture in serum-free medium on ECM proteins, especially on laminin (LM), but not on serum albumin. This effect of LM was inhibited by an anti-integrin beta 1 chain (CD29) mAb, as well as by an anti-CD3 mAb, indicating an important role of the beta 1 integrin-mediated interaction with ECM proteins in regulating persistent cytokine gene expression in RA SFMNC, and a key role of T cells in regulating inflammatory monokine production.

Adult↗

A possible role of two hydrophobic amino acids in antigen recognition by synovial T cells in rheumatoid arthritis.

Synovial T cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA) synovitis. We have quantitatively analyzed the T cell receptor (TcR) variable (V) region gene repertoire of freshly isolated synovial fluid (SF) T cells, comparing it with that of peripheral blood (PB) T cells in RA. The TcR V gene repertoire of PB and SF T cells in RA and osteoarthritis was heterogeneous. In contrast, V alpha 11 in SF was expressed to a greater degree in three of five RA patients, and increased levels of V beta 6, 1-3 were found in the SF of four of six RA, compared with paired PB. Of note, V beta 6, 1-3 was universally used in four RA patients with a disease duration of less than 10 years, irrespective of their HLA-DR types. This was in contrast to two other RA patients, suffering for more than 20 years, who showed different V alpha and V beta usages. beta-chain sequence analysis in RA patients with a preference for V beta 6, 1-3 has shown that a few clones dominated in SF, whereas polyclonality was observed in PB. These findings suggest oligoclonal expansion of T cells in response to specific antigen(s) in the SF of these patients with RA of relatively short duration. Concomitant use of two hydrophobic amino acids, leucine and valine in the D beta region was noticeable among the predominant SF clones. These two amino acids might directly contact a peptide specific for the induction of synovitis in RA patients. TcR-directed therapy may, therefore, be useful for the treatment of early RA synovitis.

Aged↗

Lymphocyte subsets in hemodialysis patients treated with recombinant human erythropoietin.

We investigated whether recombinant human erythropoietin (rhEPO) therapy affected the lymphocyte subsets in patients on long-term maintenance hemodialysis (HD) with severe anemia. Before treatment, the numbers of peripheral blood lymphocyte, CD3+, CD4+, CD8+, and CD20+ cells were decreased in HD patients compared to those in healthy subjects, while the number of CD3+HLA-DR+ cells was increased in HD patients compared to that in healthy subjects. Furthermore, the number of CD4+CD45RA+ (naive T) cells was markedly decreased in HD patients (112 +/- 77 vs 241 +/- 146/microliters; P < 0.01). The number of CD8+S6F1+ (cytotoxic T) cells in HD patients was also less than that in healthy subjects (247 +/- 104 vs 122 +/- 83/microliters; NS). During a 6-month period of rhEPO therapy, we found that the low level of CD4+CD45RA+ cells gradually increased (from 112 +/- 18 to 163 +/- 24/microliters; P < 0.01) with the elevation of hematocrit values (from 21.5 +/- 1.7 to 28.2 +/- 3.5%; P < 0.05). The number of CD3+HLA-DR+ cells decreased after 1 month of rhEPO therapy (from 93 +/- 14 to 46 +/- 13/microliters) and gradually declined throughout the 6-month study period. In our in vitro study, we demonstrated that no effects were observed on [3H]thymidine uptake in the T cell subsets at various concentrations of rhEPO. These results suggest that rhEPO-induced immunoregulation is mediated by an indirect stimulatory effect on the immune system, this stimulation being accompanied by an improvement in physical condition.

Adult↗

Fission yeast genes nda1+ and nda4+, mutations of which lead to S-phase block, chromatin alteration and Ca2+ suppression, are members of the CDC46/MCM2 family.

Fission yeast cold-sensitive mutants nda1-376 and nda4-108 display a cell cycle block phenotype at the restrictive temperature (cell elongation with the single nucleus) accompanied by an alteration in the nuclear chromatin region. DNA content analysis shows that the onset of DNA synthesis is blocked or greatly delayed in both mutant cells, the block being reversible in nda4-108. Upon release to the permissive temperature, nda4-108 cells resumed replicating DNA, followed by mitosis and cytokinesis. The nda4 phenotype was partly rescued by the addition of Ca2+ to the medium; Ca2+ plays a positive role in the nda4+ function. The predicted protein sequences of nda1+ and nda4+ isolated by complementation are similar to each other and also, respectively, to those of the budding yeast, MCM2 and CDC46, both of which are members of the gene family required for the initiation of DNA replication. The central domains of these proteins are conserved, whereas the NH2- and COOH- domains are distinct. Results of the disruption of the nda1+ and nda4+ genes demonstrates that they are essential for viability.

Amino Acid Sequence↗

A novel insertional mutation at exon VII of the myelin proteolipid protein gene in Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is an X-linked neurological disorder characterized by dysmyelination in the central nervous system (CNS). Recently mutations of the myelin proteolipid protein (PLP) gene which encodes both PLP and its isoform, DM-20 generated by alternative splicing, have been demonstrated in PMD patients. We analyzed the seven exons of the PLP gene of a Japanese boy affected with PMD by direct sequencing and identified an insertion event in exon VII of the PLP gene. This mutation was also present in his carrier mother, but was absent in ninety-five X chromosomes of normal Japanese. The frame-shift mutation leads to the production of truncated PLP with altered carboxyl terminal amino acid sequences, resulting in considerable change of the structure of PLP and DM-20 necessary for functional purposes. This is the first report of a mutation in exon VII of the PLP gene associated with PMD.

Adolescent↗

[Report of three cases of purple urine bag syndrome which occurred with a combination of both E. coli and M. morganii].

Purple urine bag syndrome is a rare phenomenon in which bags turns purple or blue following catheterization. This phenomenon was reported to occur by Providencia stuartii in the presence of indicanuria. We reported herein three females above 75 years of age having a similar phenomenon. All were bedridden chronically and constipated. In these cases, no growth of P. stuartii was found on repeated urine culture, but Escherichia coli and Morganella morganii were concomitantly isolated during the blue bags. It is suggested that purple urine bag syndrome develops in a combination of E. coli and M. morganii besides P. stuartii.

Aged↗

Philadelphia-chromosome-positive, monosomy 7 biphenotypic acute mixed lineage leukemia in adults: a pluripotent stem cell disorder.

Two adult patients with acute mixed lineage leukemia (AMLL) having combined Philadelphia chromosome (Ph1) positivity and monosomy 7 are presented. The phenotypes of leukemic blasts from both cases were almost same (early B-lymphoid lineage and myeloid lineage); CD10+, CD13+, CD19+. HLA-DR+, and dual-color analysis showed simultaneous expression of CD10 (CD19) and CD13 antigens in individual blasts (biphenotypic) in both cases. On molecular analysis, the leukemic blasts showed rearrangement in the first intron of the BCR gene with breakpoint just outside of 3' end of m-BCR-2 (bcr 3) in case 1, and in the M-BCR in case 2. Immunoglobulin heavy chain gene (IgH) rearrangement was noted in both cases, but rearrangement of the T-cell receptor beta-chain gene (TCR beta) was detected only in case 1. Clinically, both cases achieved complete remission by the combination chemotherapy consisting of L-asparaginase, doxorubicin, vincristine, and prednisolone (L-AdVP). In remission, all these molecular abnormalities disappeared in both patients. These results suggest that the Ph1-positive and monosomy 7 AMLL in adults is de novo acute leukemia with both early B-lymphoid and myeloid phenotypes and may arise from malignant transformation of pluripotent stem cell, and expresses a heterogenous rearrangement pattern of the BCR gene.

Acute Disease↗

Penetration of cefpirome into sputum in chronic respiratory infections: comparison of administration of 0.5 g and 1.0 g in the same patient.

This study evaluated the sputum penetration of cefpirome following slow intravenous infusion of 0.5 and 1.0 g using a comparative cross-over design to reduce variability. Five patients with chronic respiratory tract infections were randomized to receive either 0.5 g followed by 1.0 g, or by 1.0 g followed by 0.5 g cefpirome, by slow intravenous infusion over 1 h, with a 24-h wash-out period between each treatment. With the exception of one patient, sputum concentration correlated well with plasma concentration. Higher sputum levels of cefpirome were achieved following the higher dose.

Adult↗

[Long-term hypertension control in a community--comparison of stroke incidence and hypertension control between participants and nonparticipants in health examinations].

Since 1969, community-based hypertension control program has been conducted for non-company-employed residents aged 40 and over (3,039: 70% of the residents) in Noichi town, Kochi prefecture. The program is composed of annual health examinations, health education and referral of hypertensives to local physicians. Incidence and mortality of stroke have declined along with a decrease in systolic blood pressure levels. However, during the period of 1982-84, stroke incidence was higher for nonparticipants in health examinations than in the participants of the same age group. For an understanding of the state of detection and control of hypertension in nonparticipants aged 40-69 of the 1982-84 health examinations, blood pressure was examined for 312 subjects randomly selected from the 2,062 nonparticipants. Blood pressure levels were significantly higher in nonparticipants than in participants. In addition, the proportion of hypertensives who were aware of their blood pressure levels was lower in nonparticipants than in participants. About 87% of residents aged 40-69 reported that they received blood pressure checkups at least once a year. Persons who were involved in manual labor, sales and services received blood pressure checkups less frequently. Among company employees, the proportion of persons who checked their blood pressures annually was progressively lower with decrease in size of companies. The community hypertension control appears to have contributed to a decline of blood pressure levels and stroke incidence. However, detection and control of hypertension was relatively poor in nonparticipants in health examinations, particularly for employees of small companies.

Adult↗

[A case of surgically resected primary pulmonary lymphoma with IgG-paraproteinemia: gene analysis was effective for establishing its diagnosis].

A 69-year-old woman was hospitalized because of abnormal lung shadow and IgG-lambda paraproteinemia. She was otherwise healthy and asymptomatic. Chest roentgenogram showed a consolidation in the right lower lobe. Chest CT showed a tumour in S8 and subpleural interstitial shadow in S10. No intrathoracic lymphadenopathy was found. Serum IgG was 6,109 mg/dl. The cell count obtained by bronchoalveolar lavage (BAL) was 44.5% plasma cells and 17.5% lymphocytes. CD19-positive lymphocytes were prominent. The IgG/albumin ratio was 13 times higher, and IL-6/albumin ratio was 29 times higher in lavage fluid than in serum. Transbronchial lung biopsy (TBLB) specimen showed interstitial infiltration of plasma cells and lymphocytes. Right lower lobectomy was performed, and serum IgG subsequently decreased to about 4,000 mg/dl. DNA was extracted from the surgical specimen, and analyzed by Polymerase Chain Reaction (PCR) method. A rearrangement band was amplified with Fr3a & VLJH primers (immunoglobulin heavy chain gene). The infiltrated cells were proved to be monoclonal B-cells. This case was diagnosed as small lymphocytic lymphoma, plasmacytoid. Most primary pulmonary lymphomas are well differentiated B-cell type, and the histopathological findings resemble those of LIP or pseudolymphoma. Gene analysis may thus be an effective procedure for the distinction between inflammatory and neoplastic cell proliferation, such as LIP and lymphoma.

Aged↗