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Biomedical subjects

M Okamoto

Publications and source records attributed to M Okamoto.

At least 361 records · Page 20Linked to original sources

WA8242A1, A2 and B, novel secretory phospholipase A2 inhibitors produced by Streptomyces violaceusniger. II. Biological properties.

WA8242A1, A2 and B, novel inhibitors of secretory phospholipase A2 (PLA2), were obtained from Streptomyces violaceusniger No. 8242. WA8242B inhibited secretory group I and II PLA2s in a dose-dependent manner. The mode of inhibition of group II PLA2 by WA8242B was in competitive fashion. WA8242B inhibited group II PLA2-induced Prostaglandin I2 (PGI2) production by human umbilical vein endothelial cells. Furthermore, WA8242B was effective in mouse zymosan writhing model.

2-Aminoadipic Acid↗

[Effectiveness of day care service for elderly patients with dementia and their caregivers as observed by comparison of days with and without day care services].

PURPOSE: To explore the effectiveness of day care service for the dementia elderly and their caregivers. METHODS: Subjects were sixty caregivers who took care of dementia elderly and were using day care service in two municipalities. The data on caregiving, care burden of caregivers, and time schedule of daily life were obtained from a questionnaire that was distributed at the five day care centers and collected through home visits. The data from a day with day care were compared with data from a day without. RESULTS & DISCUSSION: 1. Caregivers reported that their care burden was reduced on the day with day care, even though their time schedule for the day was not so different from the day without day care. 2. The harder the caregiving became, the more caregivers felt relieved on the day with day care. 3. Obviously, day care would no be expected to have the same effect in situations in which the caregiver is elderly or works outside the home all day. CONCLUSION: When we think about day care it is important to provide a well adapted home care program which effectively meets the needs of the dementia elderly and their caregivers.

Adult↗

Development of prototype full-automatic environmental control system for nitrox saturation diving.

A full-automated hyperbaric environmental control system (HECS) for nitrox saturation diving HABITAT has been examined since 1994. HECS was planned to be located inside HABITAT and operated automatically by supplying electricity and cooling water. To realize this, a regenerative-type carbon dioxide removal method and AC 100 V electric powered blower system were developed as key technology. By using molecular sieves as an adsorbent material for carbon dioxide, automated sequence for adsorbent and regeneration could be successfully realized. Also, by using solid-state conductor circuit, an AC 100 V type blower to use under hyperbaric conditions could be developed. A prototype HECS was manufactured and settled in JAMSTEC diving simulator for further evaluation.

Adsorption↗

[Use of normal human hepatocytes in a hybrid organ system].

Using the bioreactor model developed by J. Gerlach, we examined the potential of normal human hepatocytes for application in bioartificial liver devices. From normal human donor livers 1.5 x 10(8) hepatocytes were isolated. Hepatocytes were perfused in a woven multi-compartment capillary system in serum-free culture medium containing ammoniachloride over a period of 2 weeks. These cells demonstrated a well differentiated ultrastructure with formation of junctional complexes and bile canaliculi between adjacent cells. During reactor run, a constant albumin synthesis with levels above 11 mg/ml and maintenance of urea production and lignocaine metabolism (MEGX-test) were detected. These initial results indicate that normal human hepatocytes express typical morphology and ultrastructure and are able to keep differentiated functions in suitable perfusion models. Combination of the distinct human liver cell populations might enable promotion of further specific functions (clotting factors) and induction of liver cell proliferation.

Cell Survival↗

[Effects of uvulopalatopharyngoplasty on patients with obstructive sleep apnea--the severity of preoperative tonsillar hypertrophy].

Predicting outcome following uvulopalatopharyngoplasty (UPPP) in obstructive sleep apnea is difficult. We hypothesized that UPPP is effective in obstructive sleep apnea patients with severe tonsillar hypertrophy. We examined the relationship between the severity of pre-operative tonsillar hypertrophy and the effect of UPPP in 38 patients with obstructive sleep apnea (oxygen desaturation index (ODI) > or = 20). The patients were classified into three groups according to the Mackenzie Classification of tonsillar hypertrophy. Ten patients were classified as grade 1 (M1) hypertrophy, i.e. tonsils just visible beyond the palatal arch. Five patients had grade 3 (M3) hypertrophy, i.e. tonsils appearing to contact each other at the midline. The remaining 23 patients had grade 2 (M2) hypertrophy, i.e. intermediate enlargement. We measured the apnea index, ODI, DST 90, and DST 85 (%time with SaO2 < or = 90% and < or = 85%, respectively) using a screening device for sleep apnea (Apnomonitor II, CHEST M. I. Co. Tokyo, Japan) before and after UPPP. Following UPPP, the mean ODI decreased significantly in all groups: 59 to 9/hr (p < 0.005) in the M3 group, 53 to 27/hr (p < 0.001) in the M2 group, and 48 to 33/hr (p < 0.05) in the M1 group. Post-UPPP ODI decreased by 83% in M3, 45% in M2, and 28% in M1 patients. Successful UPPP, defined by a post-UPPP ODI of less than 20/hr and a greater than 50% decrease in post-UPPP ODI, occurred in 80% of M3, 43% of M2, and 10% of M1 patients. We conclude that tonsillar hypertrophy can predict a successful response to UPPP in obstructive sleep apnea patients.

Adult↗

Inhibition of human immunodeficiency virus type 1 replication and cytokine production by fluoroquinoline derivatives.

We have recently identified 8-difluoromethoxy-1-ethyl-6-fluoro-1, 4-dihydro-7-[4-(2-methoxyphenyl)-1-piperazinyl]-4-oxoquinoline-3-carb oxylic acid (K-12) as a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) transcription. In the search for more effective derivatives and their mode of action, we have found 7-(3,4-dehydro-4-phenyl-1-piperidinyl)-1, 4-dihydro-6-fluoro-1-methyl-8-trifluoromethyl-4-oxoquinoline-3- carboxylic acid (K-37) and 8-difluoromethoxy-1,4-dihydro-6-fluoro-7-(3, 4-dehydro-4-phenyl-1-piperidinyl)1-[4,(1,2, 4-triazol-1-yl)methylphenyl]-4-oxoquinoline-3-carboxylic acid (K-38) to be more potent inhibitors of HIV-1 replication than K-12. The EC50 values of K-37 and K-38 for HIV-1IIIB were 27 and 3.8 nM in peripheral blood mononuclear cells, respectively. These values were approximately 3- and 24-fold lower than the EC50 of K-12. K-38 was also a more potent inhibitor of HIV-1 replication in chronically infected cells, such as tumor necrosis factor alpha-stimulated OM-10. 1 cells. K-37 and K-38 proved to be more cytotoxic than K-12 for a variety of cell lines as well as peripheral blood mononuclear cells. These compounds were more inhibitory of Tat-induced HIV-1 long terminal repeat-driven gene expression than K-12, which suggests that their mechanism of action is attributable in part to the inhibition of Tat function. Interestingly, K-37 and K-38 could suppress the production of tumor necrosis factor alpha and interleukin 6 in phytohemagglutinin-stimulated peripheral blood mononuclear cells and the expression of intercellular adhesion molecule 1 in tumor necrosis factor alpha-stimulated human umbilical vein endothelial cells at their nontoxic concentrations. In contrast, another K-12 derivative, 1, 4-dihydro-8-dimethylaminomethyl-6-fluoro-7-[4-(2-methoxyphenyl)-1-pip eradinyl]-1-methyl-4-oxoquinoline-3-carboxylic acid (K-42), had anti-HIV-1 activity and cytotoxicity profiles similar to those of K-12, but K-42 scarcely inhibited the cytokine production and intercellular adhesion molecule 1 expression.

Anti-HIV Agents↗

[Necrosis of the hepatocellular carcinoma nodule can aggravate metastasis].

Since the stroma of hepatocellular carcinoma is composed of sinusoid-like structures, cancer cells are readily released from the primary tumor with possible injurious consequences. A 63-year-old woman with hepatocellular carcinoma underwent percutaneous ethanol injection therapy. During this treatment, tumor thrombus developed in the right hepatic vein. Partial hepatic resection was performed. Six months later, multiple nodules appeared in the lung fields. Partial necrosis may have allowed the release of cancer cells from the primary tumor. Perioperative therapy should have an effect on intrahepatic micrometastases, because removal of the main tumor can be done surgically.

Carcinoma, Hepatocellular↗

Evaluation of the function of primary human hepatocytes co-cultured with the human hepatic stellate cell (HSC) line LI90.

Most bioartificial liver devices utilise primary hepatocytes alone although some have considered the use of non parenchymal cells in addition. However the effects of co-culture of human hepatocytes with different sinusoidal cell types has not been fully investigated. In this study we have examined the influence of co-culturing primary human hepatocytes with the human hepatic stellate cell (HSC) line, LI90. Cultures were monitored by light microscopy and on days 4, 8 and 14 urea synthesis and cytochrome P450 activity were measured. Morphologically LI90 cells proliferated to fill spaces between and into adjacent islands of hepatocytes. On day 14 cytochrome P450 activity in co-culture was significantly improved compared to hepatocytes cultured alone. By contrast, urea synthesis in hepatocytes was unaffected by single or co-culture. Therefore it can be concluded that a combination of primary human hepatocytes with LI90 cells is beneficial for growth and some stability of hepatocytes and may therefore be appropriate for seeding bioartificial liver devices.

Cell Division↗

[Requirement of class II and membrane proximal region of mouse mammary tumor virus superantigen (Mtv SAG) in Mtv7 SAG presentation].

Although in some cases superantigens (SAGs) have been shown to bind directly to T cell receptor (TCR) in the absence of MHC molecules, the precise role of MHC class II in SAG presentation to T cells is not thoroughly understood. In particular, it is still not known whether MHC class II is a mere transporter of mouse mammary tumor virus (Mtv) SAG to the cell surface or an essential component complexed with SAGs for TCR triggering. In this study, we found that MHC class II negative B cell line transfected with CD72/Mtv7 sag chimeric gene could express the Mtv7 SAG on the cell surface. The murine B cell line M12.4.1 and its MHC class II negative mutant, M12C3 are transfected with CD72/Mtv7 sag chimeric gene. Although both transfectants expressed Mtv7 SAG on their cell surface, M12.4.1 but not M12C3 activated Mtv7 SAG responding T cell hybridomas. The results argue that the mere presence of Mtv7 SAG on the cell surface does not effectively transmit the signal to TCR. As MHC class II-positive cells transfected with CD72/Mtv7 sag gene caused T cell activation, the cytoplasmic/transmembrane portion of Mtv7 SAG is not essential for T cell activation. In order to examine the importance of the membrane proximal region of Mtv7 SAG in T cell activation, we constructed chimeric genes between the encoding cytoplasmic/transmembrane portion of CD72 and N-truncated extracellular region of Mtv7 sag (CD72/ATG3, CD72/ATG5). Despite the expression of Mtv7 SAG on the cell surface, cells transfected with CD72/ATG3 or CD72/ATG5 genes were unable to stimulate Mtv7 SAG responding T cell hybridomas. The results indicate that 54 extracellular amino acids (the difference between CD72/Mtv 7 SAG and CD72/ATG3) located proximal to the membrane may be important for Mtv7 SAG function.

Animals↗

[Type A acute aortic dissection: late reoperations for dilatation of the distal false lumen and aortic regurgitation].

From January 1990 to December 1996, 71 patients aged 33 to 79 years (mean 60 +/- 11) underwent an emergency operation for type A acute aortic dissection. Fifty-three (74.6%) survived, and were followed 7 to 94 months (mean follow up 2.9 +/- 1.8 years) after the first operation. Five patients underwent reoperation for dilatation of the distal false lumen 7 to 52 months (mean period, 25 months) after primary repair. One patient underwent replacement of the arch and descending aorta, three patients underwent replacement of the descending aorta, and one patient underwent the stented graft implantation, resulting in closure of the entry site. Three patients underwent reoperation for severe aortic valve regurgitation 12 to 31 months (mean period, 24 months) after primary repair. Two patients underwent aortic valve replacement, and one patient underwent aortic root replacement. The actuarial freedom from reoperations was 81 +/- 6.9% at 3 years, and 73 +/- 9.9% at 5 years.

Adult↗

What kind of patients are suitable for evaluating the therapeutic effect of sudden deafness?

OBJECTIVE: This study aimed to find out appropriate patients to evaluate the therapeutic effect of sudden deafness. STUDY DESIGN: The study design was a retrospective case review. SETTING: The study was performed at a university hospital. PATIENTS: A series of 443 patients with idiopathic sudden sensorineural hearing loss who visited the authors within 1 week from the onset participated. INTERVENTIONS: Relationship between interval from the onset and treatment prognosis was investigated. RESULTS: The significant difference in prognosis related to the days from the onset to the initial visit was noted only in the patients with the initial hearing level from 50-65 dB. The prognosis of the patients who visited the authors on the next day from the onset was excellent. Whereas, in the patients with initial hearing level worse than 70 dB, no significant difference in prognosis was noted among the days of visit. CONCLUSIONS: The patients with the initial hearing level worse than 70 dB and who visited the authors within 8 days from the onset were appropriate for candidates in evaluating the therapeutic effect of sudden deafness.

Adult↗

[Changes in intraoperative blood glucose and ketone body concentrations during the repair of lipomyelomeningocele in children].

Blood glucose and ketone body (3-hydroxy-butyrate) concentrations were measured in 8 children (4.2 +/- 2.8 years old) during the repair of lipomyelomeningocele (9.0 +/- 2.6 hours) to elucidate whether lipid mobilization can be prevented by glucose infusion at the rate of 0.2 +/- 0.05 g.kg-1.h-1. The operation was followed in about 4 hours by a significant increase in blood glucose and ketone body concentrations, with their maximum value of 195 +/- 75 mg.dl-1 and 656 +/- 75 mumol.l-1, respectively (P < 0.05), as compared with the preoperative level. The lipid mobilization soon returned to normal state by increasing the rate of glucose infusion, as indicated by ketone body level of 92 +/- 58 mumol.l-1 at the end of operation. These results show that glucose infusion rate should be adjusted based on serial analysis of both blood sugar and ketone body concentrations in the anesthetic management of children undergoing a long operation.

3-Hydroxybutyric Acid↗

Mints, Munc18-interacting proteins in synaptic vesicle exocytosis.

Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1. Mint proteins are detectable only in brain and are composed of an N-terminal sequence that binds Munc18-1, a middle phosphotyrosine-binding domain, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane. In brain, Mint proteins are part of a multimeric complex containing Munc18-1 and syntaxin that likely functions as an intermediate in synaptic vesicle docking/fusion. The phosphotyrosine-binding domain specifically binds to phosphatidylinositol phosphates known to be produced during vesicle exocytosis (Hay, J. C., Fisette, P. L., Jenkins, G. H., Fukami, K., Takonawa, T., Anderson, R. A., and Martin, T. F. J. (1995) Nature 374, 173-177). Our data suggest a model whereby local production of phosphatidylinositol phosphates may trigger the binding of vesicles to the active zone via the Mint.Munc18-1 complex in conjunction with syntaxin 1.

Adaptor Proteins, Signal Transducing↗

Polyadenylation-mediated translational regulation of maternal P450(11beta) mRNA in frog oocytes.

Northern blot analysis of bullfrog tissues using a cDNA probe of cytochrome P450(11beta) showed that a large amount of message was present in the ovary as well as in the adrenal tissue. Two kinds of mRNA of different sizes were found in the ovary. Sequence determination of the two cDNAs and analysis by reverse-transcription polymerase chain reaction indicated that the protein encoded by the larger mRNA was identical to the adrenal enzyme, while the protein encoded by the smaller had a truncated sequence lacking an extension peptide necessary for the protein transport to the mitochondria. The mRNAs were present in the oocytes but not in the follicular cells, and their content in an oocyte varied little during its maturation. Immunoblot analyses of the mitochondrial fraction of oocytes failed to demonstrate the presence of P450(11beta) protein. In contrast the eggs were found to contain a large amount of enzymatically active protein. Interestingly the mRNA has a cis-element called cytoplasmic polyadenylation element at its 3' untranslated region. When poly(A) tails of the message prepared from eggs and oocytes were examined by RNase H digestion or reverse-transcription polymerase chain reaction, those of eggs were about 150 nucleotides longer than those of oocytes. These results suggest that translation of the message is stimulated during the oocyte maturation as a result of enhanced polyadenylation at its 3'-end. Finally a finding is presented that progesterone was converted to 11beta-hydroxyprogesterone by the frog P450(11beta), implying that the enzyme expressed in eggs may control a level of progesterone which is needed to initiate the oocyte maturation.

Animals↗

Establishment of human peripheral lung epithelial cell lines (HPL1) retaining differentiated characteristics and responsiveness to epidermal growth factor, hepatocyte growth factor, and transforming growth factor beta1.

Novel human epithelial cell lines retaining characteristic features of normal peripheral airway cells were established by transfecting the SV40 large T antigen gene into primary in vitro outgrowths from normal peripheral lung specimens. These lines, designated as HPL1A to HPL1E, showed the polygonal shapes typical of epithelial cells and expressed cytokeratin in abundance. Ultrastructural examination revealed the presence of microvilli, multivesicular bodies, and multilamellar body-like structures that are characteristic of type II pneumocytes, but expression of CC1O transcripts, a highly specific marker for Clara cells, was also observed. Response to transforming growth factor beta, epidermal growth factor (EGF), and hepatocyte growth factor, all of which are thought to be important growth-regulatory molecules for cellular proliferation and developmental processes of peripheral lung, was apparent. In the HPL1A case, markedly altered cell morphology and cytoskeletal organization, potent inhibition of cell growth, and increased expression of an extracellular matrix protein were noted with transforming growth factor beta. Interestingly, both EGF and hepatocyte growth factor stimulated anchorage-dependent growth, whereas only EGF could sustain anchorage-independent proliferation. The HPL1 lines are, to our knowledge, the first series of stable epithelial lines of human peripheral lung to be described. They should be valuable for investigating various aspects of growth regulation and oncogenic processes, including the mechanisms of acquisition of anchorage independence and the interrelationships of genetic changes identified previously in lung cancers. In addition, the HPL1 lines may also prove useful for development of in vitro models for other human lung disorders as well as to elucidate the mechanisms of peripheral lung differentiation.

Aged↗

Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion.

Rab3 is a neuronal GTP-binding protein that regulates fusion of synaptic vesicles and is essential for long-term potentiation of hippocampal mossy fibre synapses. More than thirty Rab GTP-binding proteins are known to function in diverse membrane transport pathways, although their mechanisms of action are unclear. We have now identified a putative Rab3-effector protein called Rim. Rim is composed of an amino-terminal zinc-finger motif and carboxy-terminal PDZ and C2 domains. It binds only to GTP (but not to GDP)-complexed Rab3, and interacts with no other Rab protein tested. There is enrichment of Rab3 and Rim in neurons, where they have complementary distributions. Rab3 is found only on synaptic vesicles, whereas Rim is localized to presynaptic active zones in conventional synapses, and to presynaptic ribbons in ribbon synapses. Transfection of PC12 cells with the amino-terminal domains of Rim greatly enhances regulated exocytosis in a Rab3-dependent manner. We propose that Rim serves as a Rab3-dependent regulator of synaptic-vesicle fusion by forming a GTP-dependent complex between synaptic plasma membranes and docked synaptic vesicles.

Adaptor Proteins, Signal Transducing↗