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Biomedical subjects

M Noma

Publications and source records attributed to M Noma.

At least 37 records · Page 2Linked to original sources

[A case of large congenital right ventricular outflow aneurysm].

A rare case of large congenital right ventricular outflow aneurysm is reported. A 5-year-old girl had been diagnosed as having atrial septal defect and pulmonary valvular stenosis. A large cavity in front of right ventricular outflow was noticed by her follow-up echocardiography. The non-contracting cavity was confirmed as an aneurysm originating from right ventricular outflow tract by angiocardiogram. Surgical resection was performed successfully with concomitant atrial septal defect closure and pulmonary valvular commissurotomy. Histological examination revealed that the wall of the ventricular outflow aneurysm consisted of dense fibrous tissue, contained no myocardium, and the cavity was lined with endocardium. It is reported that rupture of congenital ventricular aneurysm may occur even if there is no symptom. Surgical resection will be recommended especially when increasing in size is diagnosed.

Cardiac Surgical Procedures↗

The effects of ivermectin on onchocercal skin disease and severe itching: results of a multicentre trial.

OBJECTIVE: To determine the effects of ivermectin in annual, 3-monthly and 6-monthly doses on onchocercal skin p6isease (OSD) and severe itching. METHOD: A multicentre, double-blind placebo controlled trial was conducted among 4072 residents of rural communities in Ghana, Nigeria and Uganda. Baseline clinical examination categorized reactive skin lesions as acute papular onchodermatitis, chronic papular onchodermatitis and lichenified onchodermatitis. Presence and severity of itching was determined by open-ended and probing questions. Clinical examination and interview took place at baseline and each of 5 subsequent 3-monthly follow-up visits. RESULTS: While prevalence and severity of reactive lesions decreased for all 4 arms, those receiving ivermectin maintained a greater decrease in prevalence and severity over time. The difference between ivermectin and placebo groups was significant for prevalence at 9 months and for severity at 3 months. Differences between placebo and ivermectin groups were much more pronounced for itching. From 6 months onward, the prevalence of severe itching was reduced by 40-50% among those receiving ivermectin compared to the trend in the placebo group. CONCLUSION: This is an important effect on disease burden as severe itching is for the affected people the most troubling complication of onchocerciasis. The difference among regimens was not significant, and the recommended regimen of annual treatment for the control of ocular onchocerciasis appears also the most appropriate for onchocerciasis control in areas where the skin manifestations predominate. The final determination of the effect on skin lesions requires a longer period of study.

Adult↗

Delivery systems and cost recovery in Mectizan treatment for onchocerciasis.

The efficiency of on-going delivery systems and cost recovery in Mectizan (ivermectin, MSD) treatment for onchocerciasis are reviewed. The search is on for an effective system of Mectizan delivery, involving drug procurement, delivery from port to districts and distribution to eligible persons, which can be sustained by the endemic countries for many years. The mechanisms for procuring and clearing the drug at the ports, and the drug's integration into the existing delivery systems of each national health service, need to be improved. Although large-scale treatments by mobile teams or community-based methods evidently achieve high and satisfactory rates of coverage, they also incur high recurrent costs which have to be covered by external partners and are not sustainable by national health services. Cost-sharing is considered an important factor in a sustainable delivery system and community-directed treatment, in which the community shares the cost and ownership of local distribution and is empowered to design and implement it, is likely to be more cost-effective and sustainable.

Africa↗

Morphological changes and hypomethylation of DNA in transgenic tobacco expressing antisense RNA of the S-adenosyl-L-homocysteine hydrolase gene.

S-adenosyl-L-homocysteine hydrolase (SAHH) is a key enzyme in the regulation of intracellular methylation reactions. To investigate the role of SAHH in methylation reactions and morphogenesis in planta, we have made transgenic plants expressing antisense RNA of tobacco SAHH. The transgenic plants displayed distinct morphological changes including a floral homeotic change. We hypothesized that the changes were caused by increased levels of cytokinin. In those transgenic plants, we observed that a repetitive DNA sequence appeared less methylated than controls. We speculated that altered gene expressions by the hypomethylation of DNA might be involved in the changes.

Adenosylhomocysteinase↗

[A case report of a fenestrated Fontan operation after bivalvation of the common atrioventricular valve in right isomerism].

The patient is a boy of five years old with asplenia, dextrocardia, right aortic arch, bilateral superior vena cavae, single atrium, common atrioventricular orifice, double outlet right ventricle and pulmonary stenosis. He underwent operations of right Blalock-Taussig shunt and right superior vena cava ligation when he was eight months old and at the age of three years old, bidirectional Glenn procedure and bivalvation of the common atrioventricular valve (CAVV) as he, then, suffered from severe regurgitation of the CAVV. The regurgitation improved from grade 3 to 1 and his recovery allowed the fenestrated Fontan operation at the age of four years and nine months. Bivalvation is an effective means for the mitigation of regurgitation of CAVV and paves the way for application of Fontan-type operation.

Child, Preschool↗

Successful engraftment of allogeneic CD34-enriched marrow cell transplantation from HLA-mismatched parental donors.

The CD34 antigen is expressed on pluripotent stem cells and the CD34+ cell has been shown to be capable of hematopoietic reconstitution in animal and human autologous grafts. We asked if CD34+ cells could reconstitute hematopoiesis in human allogeneic transplantation from a HLA-mismatched donor. Three pediatric patients with advanced leukemia received allogeneic CD34-enriched marrow cell graft from HLA two (two patients) or three (one patient) loci-mismatched parental donors. CD34+ cell selection was performed with mouse anti-CD34 antibody 9C5 and magnetic beads coated sheep anti-mouse IgG1. 1.53 to 2.48 x 10(9) marrow cells were processed and 2.53 to 7.89 x 10(7) positively selected cells were recovered. The selected population showed 93.7 to 99.0% CD34+ cells and total recovery of CD34+ cells from the starting population was 54.6 to 62.3%. CD34+ cell selection resulted in more than 99.9% depletion of CD5+ cells from the bone marrow. The patients received 2.53 to 7.25 x 10(6) CD34-enriched cells/kg after myeloablative therapy. All patients achieved trilineage engraftment that was confirmed by various genetic markers. Acute graft-versus-host disease (GVHD) was grade 0 (two patients) or grade I (one patient), and hematological recovery was successfully achieved as follows; the days to reach granulocytes over 0.5 x 10(9)/I were 11 to 13 days, reticulocytes over 2% was 18 to 28 days, platelets over 50 x 10(9)/I was 33 to 58 days. One patient is surviving without relapse of leukemia and two patients died after either mixed hematopoietic chimerism or leukemia relapse was observed. These studies suggest that CD34+ marrow cells are capable of hematopoietic reconstitution from HLA two or three loci-mismatched donors even with the lowest dose of mature T cells.

Adult↗

Identification of two isoforms of mouse neuropeptide Y-Y1 receptor generated by alternative splicing. Isolation, genomic structure, and functional expression of the receptors.

Two cDNA clones homologous with human neuropeptide (NP) Y-Y1 receptor have been isolated from a mouse bone marrow cDNA library. One was thought to be the cognate of the human NPY-Y1 receptor, termed Y1 alpha receptor, and the other form, termed Y1 beta receptor, differed from the Y1 alpha receptor in the seventh transmembrane domain and C-terminal tail. Analysis of the mouse genomic DNA showed that both receptors originated from a single gene. The different peptide sequences of the Y1 beta receptor were encoded by separate exons, hence, these receptors were generated by differential RNA splicing. High affinity binding of [125I]NPY to each receptor expressed in Chinese hamster ovary (CHO) cells and sequestration of [125I]NPY after binding to each receptor were observed. In the CHO cells expressing the Y1 alpha receptor, intracellular Ca2+ increase, inhibition of forskolin-induced cAMP accumulation, and mitogen-activated protein kinase (MAPK) activation were observed by stimulation of NPY, and these responses were abolished by pretreatment with pertussis toxin. Since wortmannin completely inhibited NPY-elicited MAPK activation, we speculate that wortmannin-sensitive signaling molecule(s) such as phosphoinositide 3-kinase may lie between pertussis toxin-sensitive G-protein and MAPK. In contrast, these intracellular signals were not detected in CHO cells expressing the Y1 beta receptor. Northern blots and reverse transcriptase-polymerase chain reaction analyses indicated that the Y1 alpha receptor was highly expressed in the brain, heart, kidney, spleen, skeletal muscle, and lung, whereas the Y1 beta receptor mRNA was not detected in these tissues. However, the Y1 beta receptor was expressed in mouse embryonic developmental stage (7 and 11 days), bone marrow cells and several hematopoietic cell lines. These results suggest that the Y1 beta receptor is an embryonic and a bone marrow form of the NPY-Y1 receptor, which decreases in the expression during development and differentiation.

Alternative Splicing↗

A radioreceptor binding assay for platelet-activating factor (PAF) using membranes from CHO cells expressing human PAF receptor.

A simple and reproducible radioreceptor assay (RRA) has been developed using membranes from CHO cells which can stably express human platelet-activating factor (PAF) receptor. The CHO cells expressing the PAF receptor, termed CHO.1F8, showed a significant intracellular Ca2+ response to PAF, and the same binding properties to [3H]WEB 2086, a PAF antagonist, as reported (Kd, 13.6 +/- 1.9 nM; Bmax, 2.5 +/- 0.4 pmol/mg protein (n = 6)). A competitive binding assay was done using the CHO.1F8 cell membranes and [3H]WEB 2086. The minimum detectable dose of PAF was 0.3 nM (approximately 30 pg per well) and the assay was highly specific for PAF. This method makes it possible to handle large numbers of samples rapidly and simultaneously, since the receptor membrane is prepared in advance and the binding assay can be completed within 3 h. Using this method, we have determined the production and cell association of PAF in human neutrophils.

Animals↗

Broad resistance to plant viruses in transgenic plants conferred by antisense inhibition of a host gene essential in S-adenosylmethionine-dependent transmethylation reactions.

S-Adenosylhomocysteine hydrolase (SAHH) is a key enzyme in transmethylation reactions that use S-adenosylmethionine as the methyl donor. Because of the importance of SAHH in a number of S-adenosylmethionine-dependent transmethylation reactions, particularly the 5' capping of mRNA during viral replication, SAHH has been considered as a target of potential antiviral agents against animal viruses. To test the possibility of engineering a broad type of resistance to plant viruses, we expressed the antisense RNA for tobacco SAHH in transgenic tobacco plants. As expected, transgenic plants constitutively expressing an anti-sense SAHH gene showed resistance to infection by various plant viruses. Among those plants, about half exhibited some level of morphological change (typically stunting). Analysis of the physiological change in those plants showed that they contained excess levels of cytokinin. Because cytokinin has been found to induce acquired resistance, there is also a strong possibility that the observed resistance was induced by cytokinin.

Journal Article↗

Improvement of coronary vasomotion with eicosapentaenoic acid does not inhibit acetylcholine-induced coronary vasospasm in patients with variant angina.

Impaired function of the endothelium may be a mechanism of the coronary vasospasm induced by acetylcholine. We examined whether purified eicosapentaenoic acid (EPA), a major component of fish oil, improves the coronary vasomotion in response to acetylcholine, and the effect of purified EPA on acetylcholine (ACh)-induced coronary vasospasm in 22 patients with variant angina. ACh was infused into the coronary artery both before and after 4 months of EPA treatment (EPA 1.8 g/day, n = 12). In the control group (n = 10) that did not receive EPA, the response of the coronary diameter to ACh did not change over time. In the EPA-treated group, the cholinergic response in non-spastic sites changed from vasoconstriction to vasodilation, while ACh-induced coronary vasospasm persisted at the spastic sites. Therefore, EPA treatment improved the coronary vasomotor responsiveness to ACh, but did not inhibit ACh-induced coronary vasospasm.

Acetylcholine↗

[Citrate and ionized calcium on extracorporeal circulation in pediatric cardiac surgery].

The control of optimum concentrations of ionized calcium Ca2+ during cardiopulmonary bypass is important in maintaining cardiac function and reducing reperfusion injury. Ca2+ may be in part dependent upon the serum level of citrate Cit in use of hemodiluted prime in pediatric cardiac surgery. The purpose of this study was to ascertain fluctuations of Ca2+ during bypass in relation to Cit and to study control of optimum Ca2+. Ca2+ and Cit was measured prior to and every 10 or 20 minutes during bypass in 12 children aged 21 days to 6 years. Of 6 patients (body weight less than 6 kg) received acid-citrate-dextrose (ACD) solution 20 ml before aortic declamp to give low Ca2+ for reducing reperfusion injury. Ca2+ showed initial drop and then gradually increased as the result of decreasing Cit. Ca2+ was inversely correlated with Cit (r = 0.85, p = 0.0001). When ACD 20 ml was added, Ca2+ significantly decreased from 1.00 +/- 0.13 to 0.65 +/- 0.13 mmol/l. However, Cit remained 24.3 +/- 13.3 mg/dl at the end of bypass. In conclusion, the results of this study suggest that gradually increasing Ca2+ during bypass may be related to the rate of citrate metabolism and the use of citrate for the control of Ca2+ remains questionable.

Calcium↗

[Postoperative bronchial stenosis associated with IAA complex and transendoscopic resection of intrabronchial granulation].

Problem with stenosis of the left bronchus was encountered in a patient with type B interrupted aortic arch complex after the arch reconstruction and pulmonary artery banding. Bronchoscopic study disclosed the intraluminal granulation of left bronchus and transendoscopic resection of the granulation successfully relieved the stenosis and brought the patient to full recovery.

Airway Obstruction↗

[Continuous intraarterial infusion of 5-fluorouracil plus leucovorin for liver metastases from colorectal cancer].

Between September 1990 and August 1994, 11 patients (pts) with liver metastases (mets) from colorectal cancer were treated with continuous hepatic arterial infusion chemotherapy of 5-fluorouracil (FU) plus leucovorin (LV). Eight pts had non-resectable liver mets (H3: 7, H2: 1), and 3 had residual small mets after resection of major mets. Drugs were administered via an extracorporeal infusion device connected to the hepatic arterial infusion port. 5-FU and LV were given through a 5- to 7-day continuous infusion at 500-750 mg/body/day and 30 mg/body/day, respectively, with a 3- to 4-week rest period. In the recent 6 pts, cisplatin was administered as a 2-hour infusion at 25 mg/body, one or two times simultaneously. Grade 2 toxicity was noted in two pts (18%). One was stomatitis and another was uncontrolled ascites in an advanced cirrhotic pt. The response rate in the 9 evaluable pts was 67% with 6 PR and no CR. The duration of the response was 5 to 9 months. One- and two-year survival rates were 75% and 22%, respectively. These results were superior to those of the intermittent bolus injection of 5-FU plus MMC (or epirubicin) in 40 pts from 1977 to 1994. These results suggest that continuous 5-FU plus LV arterial infusion is an effective regimen in pts with liver metastases from colorectal cancer. However, the infusion with an extracorporeal device limits the pts' quality of life. Further investigation is needed for a schedule that can be practiced for a longer period.

Aged↗

[A case of multiple liver metastasis from remnant gastric cancer responding to leucovorin.5-FU+UFT therapy].

We report a case of a 67-year-old male patient who experienced multiple liver metastasis 6 months after undergoing an operation for remnant gastric cancer. The histological classification of the cancer in gastric remnant was poorly-differentiated adenocarcinoma. The patient was treated with a low dose of LV.5-FU once a week and oral UFT as an outpatient. As a result, after 3 months of the treatment, CT showed that multiple liver lesions almost disappeared, a condition that lasted about 3 years without relapse. Toxic effects due to this treatment were temporary slight liver disfunction, mild anorexia and stomatitis. This case indicates that the regimen of LV.5-FU+UFT may be effective for multiple liver metastasis from postoperative remnant gastric cancer, enabling the patient to maintain an excellent QOL (quality of life).

Adenocarcinoma↗

[A case of supravalvular pulmonary stenosis with atrial septal defect].

We reported a case of supravalvular pulmonary stenosis with atrial septal defect (ASD) in 37-year-old man. Extended pulmonary arterioplasty with the technique of Doty's operation for supravalvular aortic stenosis was carried out with bovine pericardial patch. Pressure gradient between the right ventricle and the pulmonary artery reduced from 90 to 20 mmHg after this operation. Doty's technique could be modified and successfully applicable to supravalvular pulmonary stenosis.

Adult↗

Human 5-lipoxygenase associates with phosphatidylcholine liposomes and modulates LTA4 synthetase activity.

A Ca2+ and a phosphatidylcholine (PC) as stimulatory factors to human 5-lipoxygenase (5-LO) were assessed to examine aspects of the regulatory mechanism of 5-LO. In the presence of Ca2+ (1 microM or less), PC liposomes distinctly stimulated the dual activities of 5-LO for the production of 5-HPETE from arachidonate and for its subsequent conversion to LTA4. At the same concentration of Ca2+, 5-LO was found to bind to PC liposomes. As with 5-LO activities, the binding was dependent on the range of Ca2+ concentration. The conversion ratios of 5-HPETE to LTA4 were dependent on PC liposome concentration and reached a maximum of 50% conversion. Among the four cell membrane lipids examined, PC liposomes demonstrated the highest conversion ratio of 5-HPETE to LTA4 by 5-LO. Most of the arachidonate added to the reaction mixture localized in PC liposomes. These results confirm that the intracellular increase of Ca2+ concentration causes 5-LO to associate with the cell membrane and perform an interfacial reaction. They also suggest that this binding of 5-LO to the cell membrane enhances the subsequent conversion from 5-HPETE to LTA4.

Adenosine Triphosphate↗

X-ray structure of a pokeweed antiviral protein, coded by a new genomic clone, at 0.23 nm resolution. A model structure provides a suitable electrostatic field for substrate binding.

We have determined the crystal structure of alpha-pokeweed antiviral protein, a member of ribosome-inactivating proteins, at 0.23 nm resolution, by the molecular-replacement method. The crystals belong to the space group P2(1)2(1)2 with unit-cell dimensions a = 4.71, b = 11.63 and c = 4.96 nm, and contain one protein molecule/asymmetric unit based on a crystal volume/unit protein molecular mass of 2.1 x 10(-3) nm3/Da. The crystallographic residual value was reduced to 17.2% (0.6-0.23 nm resolution) with root-mean-square deviations in bond lengths of 1.9 pm and bond angles of 2.2 degrees. The C alpha-C alpha distance map shows that alpha-pokeweed antiviral protein is composed of three modules, the N-terminal (Ala1-Leu76), the central (Tyr77-Lys185) and the C-terminal (Tyr186-Thr266) modules. The substrate-binding site is formed as a cleft between the central and C-terminal modules and all the active residues exist on the central module. The electrostatic potential around the substrate-binding site shows that the central and C-terminal module sides of this cleft have a negatively and a positively charged region, respectively. This charge distribution in the protein seems to provide a suitable interaction with the substrate rRNA.

Amino Acid Sequence↗