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Biomedical subjects

M Umeda

Publications and source records attributed to M Umeda.

At least 127 records · Page 7Linked to original sources
PubMed1998

Clinical features of testicular non-Hodgkin's lymphoma--focus on treatment strategy.

Testicular primary non-Hodgkin's lymphoma (NHL) is said to account for about 5% of all testicular tumors and about 2% of extranodular lymphoma. From a clinical standpoint, we reviewed testicular NHL of stage IE treated at our department over the past 18 years. Among the 865 cases of NHL, 19 (2.2%) were primary testicular NHL, stage IE. The 19 patients had a median age of 62 years (range 48-77 years), all had diffuse B-cell lymphoma. Of the 19 patients, 8 were treated with radiotherapy after high inguinal orchiectomy (Group I), 4 received both postoperative radiotherapy and chemotherapy (Group II), and 7 received additional prophylactic intrathecal chemotherapy (Group III). The 5-year survival rates for Groups I, II and III were 37.5%, 50%, and 100%, respectively. None of the patients receiving prophylactic intrathecal chemotherapy had relapse in the central nervous system and all of them are alive and disease-free. Primary testicular NHL is relatively common among elderly persons, and many patients die as a result of central nervous system recurrence. These results suggest that preventive measures for central nervous system recurrence such as intrathecal injection of anticancer agents should be taken into consideration as early as at the induction of remission.

Aged↗
PubMed1998

Phosphoinositide signaling pathways in nuclei are associated with nuclear speckles containing pre-mRNA processing factors.

Phosphoinositide signal transduction pathways in nuclei use enzymes that are indistinguishable from their cytosolic analogues. We demonstrate that distinct phosphatidylinositol phosphate kinases (PIPKs), the type I and type II isoforms, are concentrated in nuclei of mammalian cells. The cytosolic and nuclear PIPKs display comparable activities toward the substrates phosphatidylinositol 4-phosphate and phosphatidylinositol 3-phosphate. Indirect immunofluorescence revealed that these kinases were associated with distinct subnuclear domains, identified as "nuclear speckles," which also contained pre-mRNA processing factors. A pool of nuclear phosphatidylinositol bisphosphate (PIP2), the product of these kinases, was also detected at these same sites by monoclonal antibody staining. The localization of PIPKs and PIP2 to speckles is dynamic in that both PIPKs and PIP2 reorganize along with other speckle components upon inhibition of mRNA transcription. Because PIPKs have roles in the production of most phosphatidylinositol second messengers, these findings demonstrate that phosphatidylinositol signaling pathways are localized at nuclear speckles. Surprisingly, the PIPKs and PIP2 are not associated with invaginations of the nuclear envelope or any nuclear membrane structure. The putative absence of membranes at these sites suggests novel mechanisms for the generation of phosphoinositides within these structures.

Animals↗
PubMed1998

Induction of apoptosis by phosphatidylserine.

Treatment of Chinese hamster ovary (CHO) cells with phosphatidylserine (PS) caused cell death in a dose-dependent manner. Other phospholipids, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid, had no effect on cell viability. The cells incubated with PS became round and underwent a dramatic reduction of cellular volume while maintaining the membrane containment of cellular contents. The PS-treatment induced chromatin condensation and extensive DNA fragmentation, with a pattern characteristic of internucleosomal fragmentation on agarose gel electrophoresis. These results indicate that PS-treatment induces apoptosis of CHO cells. This apoptosis-inducing activity was highly specific for PS, and neither of the synthetic PS analogs 1,2-diacyl-sn-glycero-3-phospho-D-serine (D-PS) and 2,3-diacyl-sn-glycero-1-phospho-L-serine induced apoptosis. Analysis using fluorescence-labeled phospholipids showed that both PS and D-PS were taken up equally and then transported to intracellular membranes, suggesting that the PS-specific induction of apoptosis was not the result of its specific internalization. These observations suggest that certain molecules which may recognize the stereo-specific configuration of PS are involved in the apoptotic process triggered by PS.

Animals↗
PubMed1998

Subgingival distribution of periodontopathic bacteria in adult periodontitis and their susceptibility to minocycline-HCl.

The purpose of this study was to investigate the distribution of several periodontopathic bacteria in adult periodontitis, their in vitro susceptibility to minocycline-HCl, and whether the efficacy of the drug changes with a decrease in bacterial susceptibility. Twenty-one patients (43 to 75 years old) with 62 periodontal lesions from pockets > or =4 mm participated in the study. After subgingival sampling, an ointment containing 2% minocycline-HCl was applied locally to the selected pockets once a week for 4 weeks. The lesions were clinically examined after 1 and 4 weeks of administration. The distribution of the subgingival microorganisms included Capnocytophaga sputigena (37.1%), Prevotella intermedia (22.6%), Porphyromonas gingivalis (22.6%), Fusobacterium nucleatum (20.1%), Actinobacillus actinomycetemcomitans (9.7%), and Eikenella corrodens (4.8%). The distribution was complex, with 76.8% of the sites containing 1 to 3 bacterial spieces. The minimum inhibitory concentration (MIC) of minocycline-HCl for each organism showed that most were inhibited by a minocycline-HCl concentration equal to or less than the MIC for reference strains. However, some clinical strains of Prevotella intermedia seemed to exihibit low susceptibility to minocycline-HCl. There were no significant differences among sites with strains exhibiting low or normal susceptibility to minocycline-HCl. The concentration of the drug applied to deep periodontal pockets inhibited the growth of most of the microorganisms investigated in this study.

Administration, Topical↗
PubMed1998

Risk indicators for harboring periodontal pathogens.

The risk for harboring 6 putative periodontal pathogens in 4 selected periodontal pockets, in whole saliva, or in either site (i.e., orally) was determined in 52 Caucasians, 49 African-Americans, 48 Asian-Americans, and 50 Hispanics living in Los Angeles. 16S rRNA PCR analysis assessed the presence of Actinobacillus actinomycetemcomitans, Bacteroides forsythus, Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens, and Treponema denticola. Step-wise regression analysis determined the relationship between the occurrence of each organism and various explanatory variables (risk indicators). Periodontal probing depth or disease severity was positively associated with all 6 study organisms. African-Americans carried an increased risk for harboring P. gingivalis in saliva (odds ratio [OR] 2.95) and orally (OR 2.66), and a reduced risk for harboring T. denticola orally (OR 0.34). Asian-Americans showed an increased risk for harboring A. actinomycetemcomitans in periodontal pockets (OR 6.63) and P. gingivalis in periodontal pockets (OR 5.39), in saliva (OR 5.74), and orally (OR 5.81). Hispanics demonstrated an increased risk for harboring A. actinomycetemcomitans in periodontal pockets (OR 12.27) and P. gingivalis in periodontal pockets (OR 6.07), in saliva (OR 8.72), and orally (OR 7.98). Age was positively associated with the prevalence of P. gingivalis in saliva (OR 1.20) and orally (OR 1.20), and of A. actinomycetemcomitans orally (OR 1.18). The male gender was a risk factor for harboring P. intermedia in periodontal pockets (OR 2.40), in saliva (OR 3.31), and orally (OR 4.25), and for harboring P. nigrescens in saliva (OR 2.85). The longer the subjects resided in the United States, the less likely A. actinomycetemcomitans was detected orally (OR 0.82). Former smokers demonstrated a decreased risk for harboring A. actinomycetemcomitans in saliva (OR 0.23). Current smokers displayed an increased risk for harboring T. denticola in periodontal pockets (OR 4.61). The number of dental visits in the past 10 years was inversely related to the prevalence of P. intermedia orally (OR 0.96). The prevalence of P. intermedia in saliva was positively associated with the length of time from the last dental visit (OR 1.01). This study suggests that genetic and/or environmental factors predispose subjects to oral colonization by putative periodontal pathogens.

Adolescent↗
PubMed1998

The utility of whole saliva to detect the oral presence of periodontopathic bacteria.

This study compared the presence of 6 periodontopathic bacteria in whole saliva and subgingival plaque of 202 subjects. The test bacteria were identified using a 16S rRNA-based PCR detection method. Each study subject contributed a whole saliva sample and a paper point sample pooled from the deepest periodontal pocket in each quadrant of the dentition. The kappa test revealed a fair agreement between the presence of Porphyromonas gingivalis, Prevotella intermedia, and Treponema denticola in whole saliva and periodontal pocket samples (kappa > 0.4). The McNemar test showed that the differences between sample types were due to a more frequent detection of the 3 organisms in whole saliva than in periodontal pocket samples (P < 0.01). Prevotella nigrescens also was detected more frequently in whole saliva than in periodontal pocket samples (P < 0.01; McNemar test). Although little agreement between samples was found for Actinobacillus actinomycetemcomitans and Bacteroides forsythus (kappa < or = 0.4), neither whole saliva nor pocket samples showed better detection for these 2 species (P < 0.01, McNemar test). The results indicate that whole saliva is superior to pooled periodontal pocket samples to detect P. gingivalis, P. intermedia, P. nigrescens, and T. denticola in the oral cavity. The detection of oral A. actinomycetemcomitans and B. forsythus with reasonably good accuracy may require both whole saliva and periodontal pocket samples.

Adult↗
PubMed1998

Pirarubicin-induced myocardial damage in elderly patients with non-Hodgkin's lymphoma.

123I-metaiodobenzylguanidine (MIBG) myocardial single photon emission computed tomography (SPECT), 123I-beta-methyliodophenyl pentadecanoic acid (BMIPP) myocardial SPECT, and holter ECG recording were performed in patients with non-Hodgkin's lymphoma who underwent chemotherapy including pirarubicin (THP), in an attempt at early detection of cardiac toxicity from THP. Twenty-six patients with untreated non-Hodgkin's lymphoma who received THP-COPBLM therapy were studied. For THP-COPBLM therapy. THP was administered at a dose of 40 mg/m2 every 21 days and the total dose was 250 mg/m2 on average (40 approximately 400 mg/m2). 1) The washout rate (WR) correlated with the total THP dose, and was considered to be a useful index of cardiac sympathetic nervous dysfunction. 2) The left ventricular ejection fraction (LVEF) correlated negatively with the total dose of THP. 3) The total dose of THP showed a correlated positively with the extent score and severity score determined by BMIPP. 4) The WR correlated with the frequency of premature ventricular contraction. Animal studies have indicated that THP has less cardiac toxicity than doxorubicin, but the present study showed that cardiac toxicity occurred at a total THP dose of about 360 mg/m2 in elderly patients. Accordingly, when THP is used to treat elderly patients, multimodal evaluation of cardiac is necessary to detect cardiotoxicity and to determine the optimal dosage.

3-Iodobenzylguanidine↗
PubMed1998

[Clinical study of elderly patients with non-Hodgkin's lymphoma arising in the thyroid].

The study group comprised 10 patients who were referred between 1992 and 1996 with non-Hodgkin's lymphoma arising in the thyroid gland. There were three men and seven women, with a median age of 75 years, and seven of the group had a history of Hashimoto's disease. All 10 patients had hypothyroidism; anti-microsomal antibody was positive in six. The lymphoma was of the diffuse type in all patients (B cell, 9; T cell, 1). Five patients had stage I and five had stage II. Generally, four courses of COP-BLAM therapy were given, followed by radiotherapy (30 Gy). Complete remission was achieved in all patients, and they remained alive and disease-free for a median period of 40 months. Ultrasonography revealed diffuse, an-or hypoechoic confluent nodules, and there was intensification of the posterior acoustic enhancement in most patients. With early diagnosis non-Hodgkin's lymphoma arising in the thyroid of elderly patients, mainly women, can be cured with chemotherapy and radiotherapy.

Aged↗
PubMed1998

[A clinical study of primary lymphoma of bone].

Primary non-Hodgkin's lymphoma (NHL) of bone is a rare disease, accounting for less than 1% of all NHL cases and 3-5% of all extranodal lymphoma cases. Of 512 NHL patients treated at our department, 9 patients (1.8%, median age of 54 years) had primary NHL of bone. The disease was histologically of the diffuse type in all a patient, and of the large cell type in 6. The disease was at stage 1 in 8 patients and stage II in 1. The patients all received radiotherapy of 30-40 Gy following either the CHOP or COP-BLAM chemotherapy regimens. Treatment achieved complete remission in 8 patients. Six patients still alive (median follow-up: 63 months). It has been reported that survival is longer for patients treated with a combination of chemotherapy and radiotherapy than those, treated with radiotherapy alone. Consequently, we conclude that the standard treatment course for primary NHL of bone should be chemotherapy followed by radiotherapy.

Adult↗
PubMed1997

Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene 6.

Gas6, a product of a growth arrest-specific gene 6, potentiates proliferation of vascular smooth muscle cells and prevents cell death of vascular smooth muscle cells. It has been also demonstrated that Gas6 is a ligand of receptor tyrosine kinases Axl, Sky, and Mer. Gas6 contains gamma-carboxyglutamic acid residues, which are found in some blood coagulation factors and mediate the interaction of the coagulation factors with negatively charged phospholipid. In this study, we clarified that Gas6 specifically bound to phosphatidylserine and the binding was dependent on Ca2+ and gamma-carboxyglutamic acid residues. Furthermore, we found that U937 cells, which express Gas6 receptor on their surfaces, adhered to phosphatidylserine-coated enzyme-linked immunosorbent assay (ELISA) plate only in the presence of Gas6 and Ca2+. U937 cells also bound to ELISA plate coated with phosphatidylinositol, but the binding was independent of Gas6 and Ca2+. On the other hand, U937 cells did not adhere to phosphatidylcholine- or phosphatidylethanolamine-coated ELISA plate even in the presence of Gas6 and Ca2+. These findings suggest that Gas6 may play a role in recognition of cells exposing phosphatidylserine on their surfaces by phagocytic cells, which is supposed to be one of the mechanisms for clearing dying cells.

Animals↗
PubMed1997

Relationship between exposure to TPA and appearance of transformed cells in MNNG-initiated transformation of BALB/c 3T3 cells.

In the BALB/c-3T3-cell transformation system, the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) exposure on the appearance of transformed cells was examined in order to investigate the mechanisms of in vitro tumor promotion. Optimal duration of TPA exposure on N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-initiated cells was at least 11 days. To investigate the effect of transformation frequencies of altering inoculating cell density at the replating of MNNG-exposed cells and of altering the time of starting TPA exposure, MNNG-exposed cells were replated at various inoculum sizes. With lower inoculum sizes (1 x 10(3) to 3 x 10(4) cells/dish), maximum TPA-induced transformation occurred for TPA commencement at confluence, while with higher inoculum size (1 x 10(5) cells/dish), maximum transformation frequency was observed when TPA exposure was started on day 7 after replating, being some 2 days after confluence. This may suggest that there are different mechanisms involved, depending on inoculum size, and that these may involve cell-cell interactions (at lower inoculum) and mutation expression periods (at higher inoculum). By means of redispersion experiments, it was demonstrated that the appearance of transformed cells begins on about day 7 after replating at a cell density of 1 x 10(4) cells/dish. These results suggest the usefulness of the replating method for optimizing transformation in the BALB/c-3T3-cell transformation assay, and provide insight into the time frame of expression of MNNG-initiated transformants and TPA-induced expansion of these transformants.

3T3 Cells↗
PubMed1997

Induction of differentiation of human myeloid leukemia cells by 2'-deoxycoformycin in combination with 2'-deoxyadenosine.

2'-Deoxycoformycin (dCF), a specific and potent inhibitor of adenosine deaminase, has demonstrated significant antitumor effect on lymphoid malignancies. The drug induced functional and morphologic differentiation of myeloid leukemia cells in combination with 2'-deoxyadenosine (dAd), but not dCF alone. NB4, a cell line derived from a patient with t(15; 17) acute promyelocytic leukemia (APL) underwent granulocytic differentiation when treated with all-trans retinoic acid (ATRA) or dCF plus dAd, but not with cytosine arabinoside. Pre-exposure of NB4 cells to ATRA greatly potentiated differentiation induced by dCF plus dAd, but pretreatment with dCF plus dAd before exposure to ATRA was less effective. Differentiation of NB4 cells was effectively induced by clinically applicable concentrations of dCF in combination with dAd. These findings may provide useful information about induction of differentiation in vivo.

Antibiotics, Antineoplastic↗
PubMed1997

Exposure of phosphatidylethanolamine on the surface of apoptotic cells.

In the early stages of apoptosis, phosphatidylserine (PS) is translocated from the inner side of the plasma membrane to the outer layer, which allows phagocytes to recognize and engulf the apoptotic cells. In this study we have analyzed the cell surface exposure of phosphatidylethanolamine (PE) in apoptotic CTLL-2 cells, a cytotoxic T cell line, using a tetracyclic polypeptide of 19 amino acids (Ro09-0198) which specifically recognizes the structure of PE and forms a tight equimolar complex with the phospholipid. Fluorescence microscopic analysis showed that the peptide, conjugated with fluorescence-labeled streptavidin (FL-SA-Ro), bound effectively to the cell surface of cells undergoing apoptosis in response to withdrawal of interleukin-2 from the culture media, but not to nonapoptotic cells. The binding of FL-SA-Ro to apoptotic cells was not uniform and the intense staining was observed on surface blebs of apoptotic cells. The FL-SA-Ro binding was inhibited specifically by liposomes containing PE, suggesting that PE is mainly exposed on the surface blebs of apoptotic cells. The specific binding of FL-SA-Ro to the apoptotic cells was also confirmed using a flourescence-activated cell sorter and the time-dependent cell surface exposure of PE correlated well with the exposure of PS, as detected by the binding of annexin V. This study provides the first direct evidence that PE as well as PS is exposed on the cell surface during the early stages of apoptosis, resulting in the total loss of asymmetric distribution of aminophospholipids in the plasma membrane bilayer.

Animals↗
PubMed1997

Phosphorylation of the C2 subunit of the proteasome in rice (Oryza sativa L.).

Proteasomes function mainly in the ATP-dependent degradation of proteins that have been conjugated with ubiquitin. To demonstrate the phosphorylation of proteasomes in plants, we conducted an enzymatic dephosphorylation experiment with a crude extract of rice cultured cells. The results indicated that the C2 subunit of the 20S proteasome is phosphorylated in vivo in cultured cells. An in-gel kinase assay and analysis of phospho-amino acids revealed that the C2 subunit is phosphorylated by a 40-kDa serine/threonine protein kinase, the activity of which is inhibited by heparin, a specific inhibitor of casein kinase II. The catalytic subunit of casein kinase II from Arabidopsis was also able to phosphorylate the C2 subunit. These results suggest that the C2 subunit in rice is probably phosphorylated by casein kinase II. Our demonstration of the phosphorylation of proteasomes in plants suggests that phosphorylation might be involved in the general regulation of the functions of proteasomes.

Arabidopsis↗
PubMed1997

Recognition of phosphatidylserine on the surface of apoptotic spermatogenic cells and subsequent phagocytosis by Sertoli cells of the rat.

In a primary co-culture of spermatogenic and Sertoli cells of the rat, many spermatogenic cells die by apoptosis and are subsequently engulfed by Sertoli cells. We investigated the mechanism of this phagocytosis reaction. Testicular cells from 20-day-old rats were cultured, and spermatogenic cells and Sertoli cells were separated. When the recovered spermatogenic cells were maintained without Sertoli cells, the viability of the cells decreased and they became more susceptible to phagocytosis by Sertoli cells. Phagocytosis was severely impaired when liposomes containing acidic phospholipids, such as phosphatidylserine, phosphatidylinositol, and cardiolipin, were included in the reaction, whereas those consisting of neutral phospholipids showed little effect. Such anionic liposomes were more efficiently engulfed by Sertoli cells than were the other neutral liposomes. Also, the number of spermatogenic cells that exposed phosphatidylserine to the surface increased when cells were maintained in single culture. The results indicate that upon induction of spermatogenic cell apoptosis, phosphatidylserine and probably other acidic phospholipids, which are normally localized in the inner leaflet of the plasma membrane, translocate to the outer leaflet and serve as a signal for phagocytosis by Sertoli cells.

Animals↗