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Biomedical subjects

Y Matsuo

Publications and source records attributed to Y Matsuo.

At least 73 records · Page 4Linked to original sources

Human bone marrow stroma-dependent cell line MOLP-5 derived from a patient in leukaemic phase of multiple myeloma.

The novel multiple myeloma (MM) cell line MOLP-5 and its homologous sister cell line B407, a lymphoblastoid cell line (LCL), were established from the peripheral blood of a 71-year-old Japanese patient with Bence-Jones kappa-type multiple myeloma (stage IIIB with hyperammonaemia and hypercalcaemia). The growth of MOLP-5 cells is constitutively dependent on bone marrow stroma (BST) cells; none of the cytokines tested nor the culture supernatant of the bone marrow stroma cells could support the growth of MOLP-5. Wright-Giemsa-stained MOLP-5 cells showed typical plasma cell morphology with abundant cytoplasm and one to three nuclei. The immunoprofile of MOLP-5 corresponds to that seen typically in primary MM cells: positive for cytoplasmic immunoglobulin (Ig) kappa light chain, CD28, CD29, CD38, CD40, CD44, CD49d, CD54, CD56, CD58, CD71, CD138 and PCA-1; the cells were negative for surface Ig and various other B-cell, T-cell and myelomonocyte-associated immunomarkers. Interleukin 6 (IL-6) receptor mRNA was found in the reverse transcriptase polymerase chain reaction (RT-PCR) analysis. IL-6 and IL-10 could induce cellular proliferation in short-term induction experiments. IL-6 or IL-10 production was not detected by specific enzyme-linked immunoabsorbent assay (ELISA). MOLP-5 cells expressed parathyroid hormone-related protein (PTHrP) at the mRNA level. Cytogenetic analysis showed the typical t(11; 14) chromosome abnormality. The novel MOLP-5 cell line together with the B407 B-LCL sister line will be useful model systems in the investigation of the biology of MM.

ADP-ribosyl Cyclase↗

Identification of a nuclear export signal in MKK6, an activator of the carp p38 mitogen-activated protein kinases.

Carp homologues of p38 mitogen-activated protein kinase (MAPK) and its activator MAPK kinase 6 (MAPKK6, referred to as MKK6) were identified. There exist at least two distinct carp p38s, cp38a and cp38b, both of which consist of 361 amino acids. The transcript of c38a was exclusively expressed in the ovary, whereas that of cp38b was ubiquitously expressed. Western blot analysis with anti-(phosphorylated MAPK) Ig specific to the active p38 or JNK has shown that p38 was activated in response to hypertonic stress (1 M sorbitol) in epithelioma papilosum cyprini carp epithelial cells (EPC) and that the activation of p38 proceeded faster to the maximal level than that of JNK. Carp homologue (cMKK6) of p38 activator MKK6 consists of 404 amino acids. It was expressed ubiquitously but was most abundant in the ovary. An in vitro kinase assay demonstrated that cMKK6 is an upstream activator of cp38 and cp38b in carp because it specifically phosphorylated and activated cp38a and cp38b. Interestingly, we found that cMKK6 has a nuclear export signal (NES) sequence in its N-terminal region although upstream activators of stress-activated MAPKs, p38 and JNK, do not in other animals. The NES sequence facilitated nuclear export of cMKK6 and ovalbumin. Leucine residues in the sequence were crucial for the NES activity, as the activity was lost on replacement of the leucines to alanines. The existence of an NES in cMKK6 implies the requisite of strict regulation of the p38 MAPK pathway in carp. The abundance of these components for the stress-activated pathway in the ovary might be related to ectogenetic early development.

Amino Acid Sequence↗

Sepsis in children.

BACKGROUND: Sepsis remains lethal to children. At our institution, we have noted that approximately 2% of all hospitalized patients have had sepsis. In the present study, we analyzed episodes of sepsis that occurred in our ward. METHODS: Sepsis that occurred in our institution between January 1984 and December 1998 was reviewed and analyzed. RESULTS: Three hundred and sixty-six episodes of sepsis in 244 admitted patients were analyzed. Sepsis occurred in approximately 2% of all hospitalized patients. Forty-three of 244 patients were under 1 year of age. Eighty-seven percent (212/244) of cases had underlying diseases. Hematologic disorders or neoplasms were the most common underlying disease, comprising 55% of all patients (133/244). Two-hundred and fifty-one of 366 episodes of sepsis were acquired during hospitalization. We identified 409 causative agents. There were 25 polymicrobial infections (25/366; 7%). Gram-positive bacteria comprised 68% of all organisms (280/409). Staphylococcus aureus was the most common organism, comprising 18% of causing agents (75/409). Sixty-six organisms came from the insertion of a central venous catheter. Eighty-one patients experienced recurrent episodes of sepsis. In terms of complications, respiratory distress was the most common complication (36 episodes) and there were 15 episodes of shock. Thirty-seven patients died of sepsis. Sepsis caused by Gram-negative bacteria showed significantly higher mortality than Gram-positive bacteria (11/43 (26%) vs 15/146 (10%); P= 0.053). CONCLUSIONS: In our institution, approximately 20% of septic patients were under 1 year of age and 90% had underlying diseases. The causative agents of sepsis affected the outcome.

Adolescent↗

Case of mesothelioma of the tunica vaginalis testis with characteristic findings on ultrasonography and magnetic resonance imaging.

A case of mesothelioma of the right tunica vaginalis testis in a 32-year-old man is reported. Trans-scrotal ultrasonography revealed hydrocele and multiple nodular masses measuring 1.0-4.5 cm in size attached to the parietal vaginal layer. Magnetic resonance imaging demonstrated more clearly nodular masses with irregular surfaces lined on the hydrocele cavity. Histologic diagnosis of the tumor when orchiectomized was mesothelioma. The patient has been free of disease for approximately 3 years since the treatment.

Adult↗

Combined latissimus dorsi musculocutaneous flap and free superior gluteal artery skin flap.

We used a combined superior gluteal artery skin flap and latissimus dorsi musculocutaneous flap to repair a massive tissue defect of the upper limb. This combined flap has several advantages in that the length can be more than 60 cm, it can be used as an auxilliary muscle (latissimus dorsi) and it can also be used as a sensory flap. This combined flap is useful for covering massive skin defects.

Adult↗

Skin hemodynamics during change from supine to lateral position.

The purpose of this study was to identify the skin hemodynamics during the position change from supine to lateral in patients with neurodegenerative diseases. The participants were 19 patients with neurodegenerative diseases and 12 healthy volunteers. The alteration in the total concentration of oxyhemoglobin and deoxyhemoglobin, indicative of change in blood volume, was measured in the skin of the left flank by using a portable noninvasive tissue oxygen monitor by near-infrared spectroscopy. The positions were changed from the left and right lateral with a return to the supine between each procedure. In healthy volunteers, total hemoglobin concentration (skin blood volume) increased when the position changed from supine to left lateral and decreased when changed from supine to right lateral. The decreased skin blood volume gradually recovered after a change from the supine to the right lateral position in healthy volunteers. However, it did not recover in three sporadic olivopontocerebellar atrophy (OPCA) patients with marked autonomic dysfunction and one Parkinsonian patient with severe orthostatic hypotension. Our study identified that the intracutaneous blood was changing dynamically during the position change from supine to lateral and was regulated by autonomic nerve function.

Autonomic Pathways↗

Automated search of natively folded protein fragments for high-throughput structure determination in structural genomics.

Structural genomic projects envision almost routine protein structure determinations, which are currently imaginable only for small proteins with molecular weights below 25,000 Da. For larger proteins, structural insight can be obtained by breaking them into small segments of amino acid sequences that can fold into native structures, even when isolated from the rest of the protein. Such segments are autonomously folding units (AFU) and have sizes suitable for fast structural analyses. Here, we propose to expand an intuitive procedure often employed for identifying biologically important domains to an automatic method for detecting putative folded protein fragments. The procedure is based on the recognition that large proteins can be regarded as a combination of independent domains conserved among diverse organisms. We thus have developed a program that reorganizes the output of BLAST searches and detects regions with a large number of similar sequences. To automate the detection process, it is reduced to a simple geometrical problem of recognizing rectangular shaped elevations in a graph that plots the number of similar sequences at each residue of a query sequence. We used our program to quantitatively corroborate the premise that segments with conserved sequences correspond to domains that fold into native structures. We applied our program to a test data set composed of 99 amino acid sequences containing 150 segments with structures listed in the Protein Data Bank, and thus known to fold into native structures. Overall, the fragments identified by our program have an almost 50% probability of forming a native structure, and comparable results are observed with sequences containing domain linkers classified in SCOP. Furthermore, we verified that our program identifies AFU in libraries from various organisms, and we found a significant number of AFU candidates for structural analysis, covering an estimated 5 to 20% of the genomic databases. Altogether, these results argue that methods based on sequence similarity can be useful for dissecting large proteins into small autonomously folding domains, and such methods may provide an efficient support to structural genomics projects.

Algorithms↗

Identification of a series of transforming growth factor beta-responsive genes by retrovirus-mediated gene trap screening.

Transforming growth factor beta (TGF-beta) plays important roles in the regulation of proliferation, differentiation, apoptosis, and carcinogenesis. To identify genes responsible for maintaining the phenotype induced by TGF-beta, we performed a retrovirus-mediated gene trap screening designed to isolate TGF-beta-responsive genes in human lung carcinoma cell line A549. After screening 249 trap lines, 21 were found to express the reporter beta-galactosidase gene in a TGF-beta-responsive manner. Interestingly, in large proportions of these trap lines, the reporter gene was responsive also to phorbol ester and was suppressed by gamma interferon. Fragments of all these trapped genes were recovered by 5'- and 3'-rapid amplification of cDNA ends (RACE), and in 15 out of 21 cases (71%), the TGF-beta responsiveness of the endogenous genes was confirmed by RNA blot hybridization. In at least five cases, the TGF-beta-induced upregulation was found to be cycloheximide resistant, suggesting the roles of the genes in the TGF-beta-induced primary responses. Sequence analyses revealed that 43% (9 of 21) of the trapped genes were novel and that the remainder included genes previously reported to be upregulated by TGF-beta, such as epidermal growth factor receptor and beta1 integrin, documenting the validity of this approach. Other known genes include the ones encoding the proteins associated with cell proliferation (ribosomal proteins S15a, hNRP/NAP-1, and lipocortin II), focal adhesions (paxillin), and transcriptional regulation (thyroid hormone receptor activator molecule 1 [TRAM-1]).

Blotting, Northern↗

Breast masses with peripheral rim enhancement on dynamic contrast-enhanced MR images: correlation of MR findings with histologic features and expression of growth factors.

PURPOSE: To investigate the histologic bases of rim enhancement of breast masses demonstrated on dynamic contrast material-enhanced magnetic resonance (MR) images. MATERIALS AND METHODS: Dynamic MR images of breast lesions (invasive carcinoma, n = 29; other, n = 6) in 35 women were reviewed. In each patient, subtraction images of the dynamic contrast-enhanced study were obtained, and early and delayed rim enhancement and delayed internal enhancement were evaluated. The MR findings were correlated with the ratio of microvessel density of the peripheral to the central portion of the lesion, fibrosis, and other histologic features, including expression of vascular endothelial growth factor (VEGF) and transforming growth factor ss1. RESULTS: Early rim enhancement was observed in 29% and delayed rim enhancement was noted in 60% of all patients. Small cancer nests, a high ratio of peripheral-to-central microvessel density, peripheral VEGF expression, and a low ratio of peripheral-to-central fibrosis were correlated with early rim enhancement. Delayed rim enhancement was correlated with a high degree of fibrosis and inflammatory changes. Delayed internal enhancement was correlated with a high degree of fibrosis. CONCLUSION: Rim enhancement of breast lesions at MR imaging is due to a combination of angiogenesis, distribution and degree of fibrosis, expression pattern of VEGF, and various histologic features.

Adenocarcinoma, Mucinous↗

Influence of thoracoabdominal movement on pulmonary function in patients with Parkinson's disease: comparison with healthy subjects.

Patients with Parkinson's disease (PD) may develop pulmonary dysfunction, but the pathogenesis remains unclear. We investigated a correlation between thoracoabdominal movements and pulmonary function in seven patients with PD and 14 healthy controls. We measured vital capacity (VC) and forced vital capacity (FVC) using an autospirometer, and measured chest and abdominal movements using a respiratory inductance plethysmography by fixing transducers on the rib cage and umbilicus. Patients with PD had significantly decreased % VC (90.3 +/- 17.1 vs 105.8 +/- 13.9%), chest movement (271.3 +/- 79.6 vs. 375.2 +/- 126.7% VT) and abdominal movement (217.6 +/- 93.5 vs. 247.4 +/- 100.2% VT) with 100% VT being an average volume of chest and abdomen at rest during measurement of VC. Patients with PD also had significantly decreased % FVC (74.4 +/- 20.6 vs. 97.6 +/- 14.1%), chest movement (246.2 +/- 115.2 vs. 344.5 +/- 126.4% VT) and abdominal movement (160.3 +/- 105.6 vs 207.6 +/- 104.7% VT) with 100% VT being an average volume of chest and abdomen at rest during forced maximal inspiration. Based on the results, we conclude that a reduction of % VC in patients with PD correlated with chest movements, while a reduction of % FVC correlated with abdominal movement in patients with PD.

Abdomen↗

Experimental sensitization with Japanese cedar pollen in dogs.

Japanese cedar pollinosis is a type I allergic disease mediated by immunoglobulin E (IgE) antibodies to Japanese cedar (Cryptomeria japonica) pollen antigen (CPAg). By using 22 dogs consisting of 20 dogs aged 3 months and 2 dogs aged 3 years, immunization was performed by subcutaneous injections of CPAg with aluminum hydroxide gel. Variable levels of CPAg-specific IgE antibody response were detected in 21 of the 22 immunized dogs two weeks after the second immunization. This study provided an experimental sensitization system with CPAg in dogs, which will be useful for further immunological studies on Japanese cedar pollinosis.

Animals↗

Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in diabetic rats.

The development and progression of diabetic nephropathy is dependent on glucose homeostasis and many other contributing factors. In the present study, we examined the effect of nitecapone, an inhibitor of the dopamine-metabolizing enzyme catechol-O-methyl transferase (COMT) and a potent antioxidant, on functional and cellular determinants of renal function in rats with streptozotocin-induced diabetes. Administration of nitecapone to diabetic rats normalized urinary sodium excretion in a manner consistent with the dopamine-dependent inhibition of proximal tubule Na,K-ATPase activity. Hyperfiltration, focal glomerulosclerosis, and albuminuria were also reversed by nitecapone, but in a manner that is more readily attributed to the antioxidant potential of the agent. A pattern of elevated oxidative stress, measured as CuZn superoxide dismutase gene expression and thiobarbituric acid-reactive substance content, was noted in diabetic rats, and both parameters were normalized by nitecapone treatment. In diabetic rats, activation of glomerular protein kinase C (PKC) was confirmed by isoform-specific translocation and Ser23 phosphorylation of the PKC substrate Na,K-ATPase. PKC-dependent changes in Na,K-ATPase phosphorylation were associated with decreased glomerular Na,K-ATPase activity. Nitecapone-treated diabetic rats were protected from these intracellular modifications. The combined results suggest that the COMT-inhibitory and antioxidant properties of nitecapone provide a protective therapy against the development of diabetic nephropathy.

Animals↗

Relation of body weight change to changes in atherogenic traits; a study of middle-aged Japanese obese male office workers.

We examined the effect of body weight change on the modification of atherogenic risk factors in 296 middle-aged obese male office workers without medication for hypertension, dyslipidemia, hyperuricemia or diabetes mellitus. During a 1-year education program, 39.2% of the participants could reduce their weight, and the percentage of those who lost 2 kg or more was only 17.7%. Concomitant with the decrease of weight, however, the levels of systolic and diastolic blood pressures, total cholesterol, triglyceride, uric acid and hemoglobin A1c and the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol decreased significantly, whereas the HDL cholesterol level increased significantly. In a multivariate regression analysis, in addition to the initial risk-factor level, weight change was an important factor determining the changes in atherogenic risk factors. Changes in alcohol consumption were significantly associated with the changes in systolic blood pressure and HDL cholesterol levels. Changes in cigarettes smoking also showed significant associations with the changes in triglyceride level and the ratio of total cholesterol to HDL cholesterol. These results suggest that although the education program for controlling weight may have limited success, weight reduction exhibits beneficial changes in the atherogenic risk-factor profile in middle-aged obese men.

Adult↗

Associations of body mass index and percentage body fat by bioelectrical impedance analysis with cardiovascular risk factors in Japanese male office workers.

To determine whether body mass index (BMI, kg/m2) or percentage body fat (%BF) by bioelectrical impedance analysis (BIA) better reflects the cardiovascular risk profile, we examined the associations among BMI, %BF by BIA, and cardiovascular risk factors (systolic blood pressure (SBP), diastolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C ratio, and triglycerides (TG)) in 1,217 Japanese male office workers aged 25 to 59 years. From stepwise regression analyses of cardiovascular risk factors on age, BMI, alcohol intake, and cigarette smoking, significant correlates were, in the order of relative importance: age, BMI, and alcohol intake for SBP and DBP (the cumulative percentage of variation; 14.9% and 21.3%, respectively); age, BMI, and alcohol intake (negative) for LDL-C (11.0%); BMI (negative), alcohol, and cigarette smoking (negative) for HDL-C (19.9%); BMI, alcohol intake (negative), age, and cigarette smoking for LDL-C/HDL-C ratio (23.1%); and BMI, age, cigarette smoking, and alcohol intake for Log TG (21.7%). From stepwise regression analyses using %BF by BIA as an independent factor, %BF by BIA was also significantly associated with each cardiovascular risk factor, but the decrease in explained variance for each cardiovascular risk factor was 0.2-4.5%, compared with the model using BMI as an independent factor. These results suggest that BMI may better reflect blood pressure or serum lipid profile than %BF by BIA.

Adult↗

In vitro susceptibilities to 23 antimicrobial agents of Haemophilus influenzae from pediatric patients in Japan.

One hundred eighty-six clinical isolates of Haemophilus influenzae (H. influenzae) collected from January 1996 through December 1997 from 182 pediatric patients and 16 isolates from blood or cerebrospinal fluid (CSF) of 13 patients with bacteremia and purulent meningitis collected during the last ten years were examined for in vitro susceptibilities to 23 antibiotic agents, including 3 penicillins, 9 cephalosporins, 4 carbapenems and others, as well as for their encapsulated types and beta-lactamase production. Ceftriaxone (a third generation cephalosporin) had the highest activity against the strains in this study (minimal inhibitory concentration, MIC90 of 0.025 microgram/ml) and cefditoren (a new oral cephalosporin) was the most active oral antimicrobial agent (MIC90 of 0.05 microgram/ml). Meropenem had a much higher activity against H. influenzae (MIC90 of 0.2 microgram/ml) than the other carbapenems (imipenem, MIC90 of 1.56 micrograms/ml, panipenem, MIC90 of 1.56 micrograms/ml, and biapenem, MIC90 of 3.13 micrograms/ml). Regarding the serotyping of the encapsulated strains, 172 strains (85.1%) were nontypeable and 30 (14.9%) were serotyped (24 strains of type b, 4 strains of type e, one each of type a and c). Fifteen of the strains isolated from blood and CSF were type b and one was nontypeable. Sixteen of 202 strains (7.9%) produced beta-lactamase and all of them produced both penicillinase and cephalosporinase. The production of beta-lactamase in this study was lower than that reported in previous studies [1-3]. In this study, some strains were found against which the MICs of carbapenems were very high (highest MIC of imipenem was 12.5 micrograms/ml, of panipenem was 6.25 micrograms/ml and of biapenem was 25 micrograms/ml). Therefore, we assayed the binding affinities of imipenem for each of penicillin-binding proteins (PBPs) about one of these resistant strains. In resistant strains, inhibitory concentrations (IC50) of imipenem for PBP4 and 5 were much higher than those in susceptible strains. Thus, the results demonstrate the decrease of the affinity of imipenem for PBP4 and 5. It seems, therefore, that the major factor in the resistance to imipenem of H. influenzae was the low affinity of PBP4 and 5 for the drug.

Anti-Bacterial Agents↗

Human T-lymphotropic virus type I provirus and T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is a rare type of post-thymic T-cell neoplasm, the etiology of which is unknown. Patients with T-PLL have been found to be seronegative for human T-lymphotropic virus type-I (HTLV-I), and their leukemia cells do not retain monoclonally integrated HTLV-I provirus. Recently, we have demonstrated the presence of defective HTLV-I provirus by polymerase chain reaction in the DNA extracted from peripheral blood cells or affected lymph nodes of T-PLL patients. Although there is a possibility, from our observation, that an alternative mechanism is operating in HTLV-associated leukemogenesis, it is still unknown whether and how HTLV-I can contribute to the leukemogenesis of T-PLL. In this review, we describe controversial issues and discuss a role of HTLV-I in the leukemogenesis of T-PLL.

Cell Transformation, Viral↗

Human bone marrow stroma-dependent myeloma sister cell lines MOLP-6 and MOLP-7 derived from a patient with multiple myeloma.

Human bone marrow stroma (BST)-dependent myeloma sister cell lines MOLP-6 and MOLP-7 were established from the peripheral blood of a multiple myeloma (MM) patient with IgA kappa type MM (stage IIIB). The growth of the cell lines is constitutively dependent on BST cells; none of the cytokines tested nor the culture supernatant of the BST cells could support the growth. Both cell lines showed typical plasma cell morphology with abundant cytoplasm and one to four nuclei under Wright staining. The immunoprofiles of MOLP-6 and MOLP-7 correspond to that seen typically in primary MM cells: positive for cytoplasmic immunoglobulin (Ig) chains, a heavy and kappa light chains, CD9, CD28, CD40, CD44, CD45, CD56, and PCA-1; the cells were negative for surface Igs and various other B-cell, T-cell and myelomonocyte associated markers. Both cell lines also expressed adhesion molecules including HCAM (CD44), VLA-4 (CD49d/CD29), VLA-6 (CD49f/CD29), ICAM-1 (CD54), NCAM (CD56), LFA-3 (CD58) and L-selectin (CD62L). The doubling time of MOLP-6 and MOLP-7 was 48 and 168 hours, respectively. In addition to this growth characteristic, the maximum cell density of each cell line was obtained at 1.7 x 10(6) cells/ml and 9.7 x 10(5) cells/ml, respectively. The characteristics of each cell line may reflect intraclonal variation of the proliferative capacity. The MOLP-6 together with the MOLP-7 sister will be useful model systems for the investigation of the biology of myeloma.

Antigens, CD↗

Recovery of hematopoietic progenitor cells in patients with severe aplastic anemia who obtained good clinical response with a combination therapy of immunosuppressive agents and recombinant human granulocyte colony-stimulating factor.

Seventeen patients with newly diagnosed acquired severe aplastic anemia were treated with a combination of immunosuppressive drugs consisting of anti-lymphocyte or anti-thymocyte globulin, cyclosporin A (CyA), methylprednisolone, and recombinant human granulocyte colony-stimulating factor (G-CSF). Fourteen (82%) of the 17 patients achieved good response (GR), and 3 (18%) had no response. Among the 14 GR patients, 5 (36%) later evolved clonal diseases, 1 developed myelodysplastic syndrome, and 4 developed paroxysmal nocturnal hemoglobinuria. The numbers of granulocyte-macrophage colony-forming units (CFU-GM) and erythrocyte burst-forming units were markedly low or absent in all cases before therapy. After therapy, those numbers in 13 patients among 14 responders recovered to the level of the normal control at the time of GR. However, the CFU-GM number substantially declined after that but gradually recovered again to reach a normal level over longer clinical courses. The positive rate for HLA-DRB1*1501 was 60% (3/5) among 5 CyA-dependent patients, which tended to be higher than the 20% (1/5) among 5 CyA-independent patients. Thus, immunosuppressive therapy combined with G-CSF provides a high rate of good hematological response accompanied by the apparent recovery of the hematopoietic progenitor compartments.

Adolescent↗